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11 pages, 2063 KiB

Open AccessArticle

Hyaluronan/Poly-L-lysine/Berberine Nanogels for Impaired Wound Healing

by Giovanni Amato, Maria Aurora Grimaudo, Carmen Alvarez-Lorenzo, Angel Concheiro, Claudia Carbone, Angela Bonaccorso, Giovanni Puglisi and Teresa Musumeci

Pharmaceutics 2021, 13(1), 34; https://doi.org/10.3390/pharmaceutics13010034 - 28 Dec 2020

Cited by 18 | Viewed by 3131

Abstract

Physiological wound healing process can be delayed in the presence of certain pathologies, such as diabetes or cancer. In this perspective, the aim of this study was to design a new nanogel platform of hyaluronan, poly-L-lysine and berberine suitable for wound treatment. Two [...] Read more.

Physiological wound healing process can be delayed in the presence of certain pathologies, such as diabetes or cancer. In this perspective, the aim of this study was to design a new nanogel platform of hyaluronan, poly-L-lysine and berberine suitable for wound treatment. Two different nanogel formulations were selected after a first formulation screening. They were prepared by adding dropwise 2 mg/mL hyaluronan aqueous solution (200 or 700 kDa) to 1.25 mg/mL poly-L-lysine aqueous solution. Blank nanogels formulated with 200 kDa HA resulted stable after freeze-drying with dimensions, polydispersity index and zeta potential of 263.6 ± 13.1 nm, 0.323 ± 0.029 and 32.7 ± 3.5 mV, respectively. Both blank and berberine-loaded nanogels showed rounded-shape structures. Loaded nanogels released nearly 50% of loaded berberine within 45 min, whereas the remaining 50% was released up to 24 h in vitro. Both, blank and berberine-loaded nanogels were able to completely close the fibroblasts gap in 42 h. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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28 pages, 6151 KiB

Open AccessArticle

Further Evidence of Possible Therapeutic Uses of Sambucus nigra L. Extracts by the Assessment of the In Vitro and In Vivo Anti-Inflammatory Properties of Its PLGA and PCL-Based Nanoformulations

by Ana Henriques Mota, Noélia Duarte, Ana Teresa Serra, António Ferreira, Maria Rosário Bronze, Luísa Custódio, Maria Manuela Gaspar, Sandra Simões, Patrícia Rijo, Lia Ascensão, Pedro Faísca, Ana Silveira Viana, Rui Pinto, Pradeep Kumar, António José Almeida and Catarina Pinto Reis

Pharmaceutics 2020, 12(12), 1181; https://doi.org/10.3390/pharmaceutics12121181 - 04 Dec 2020

Cited by 19 | Viewed by 2901

Abstract

Sambucus nigra L. is widely used in traditional medicine with different applications. However, confirmative studies are strongly required. This study aimed to assess the biological activities of the S. nigra flower’s extract encapsulated into two different types of nanoparticles for optimizing its properties [...] Read more.

Sambucus nigra L. is widely used in traditional medicine with different applications. However, confirmative studies are strongly required. This study aimed to assess the biological activities of the S. nigra flower’s extract encapsulated into two different types of nanoparticles for optimizing its properties and producing further evidence of its potential therapeutic uses. Different nanoparticles (poly(lactide-co-glycolide, PLGA) and poly-Ɛ-caprolactone (PCL), both with oleic acid, were prepared by emulsification/solvent diffusion and solvent-displacement methods, respectively. Oleic acid was used as a capping agent. After the nanoparticles’ preparation, they were characterized and the biological activities were studied in terms of collagenase, in vitro and in vivo anti-inflammatory, and in vitro cell viability. Rutin and naringenin were found to be the major phenolic compounds in the studied extract. The encapsulation efficiency was higher than 76% and revealed to have an impact on the release of the extract, mainly for the PLGA. Moreover, biochemical and histopathological analyses confirmed that the extract-loaded PLGA-based nanoparticles displayed the highest anti-inflammatory activity. In addition to supporting the previously reported evidence of potential therapeutic uses of S. nigra, these results could draw the pharmaceutical industry’s interest to the novelty of the nanoproducts. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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22 pages, 3516 KiB

Open AccessArticle

Safety and Photoprotective Efficacy of a Sunscreen System Based on Grape Pomace (Vitis vinifera L.) Phenolics from Winemaking

by Alexandra A. Hübner, Fernanda D. Sarruf, Camila A. Oliveira, Alberto V. Neto, Dominique C. H. Fischer, Edna T. M. Kato, Felipe R. Lourenço, André Rolim Baby and Elfriede M. Bacchi

Pharmaceutics 2020, 12(12), 1148; https://doi.org/10.3390/pharmaceutics12121148 - 27 Nov 2020

Cited by 24 | Viewed by 3456

Abstract

In winemaking, a large amount of grape pomace is produced that is rich in polyphenolics and highly beneficial for human health, as phenols are useful for skin ultraviolet (UV) protection. In this investigation, we evaluated the safety and clinical efficacy of a sunscreen [...] Read more.

In winemaking, a large amount of grape pomace is produced that is rich in polyphenolics and highly beneficial for human health, as phenols are useful for skin ultraviolet (UV) protection. In this investigation, we evaluated the safety and clinical efficacy of a sunscreen system containing a grape pomace extract from Vitis vinifera L. as a bioactive ingredient. The recovery of phenolics in the waste was performed by percolation. Nine emulsions were developed using a factorial design and two were evaluated clinically: Formulation E, containing only UV filters (butylmethoxydibenzoyl methane, ethylhexyl methoxycinnamate and ethylhexyl dimethyl PABA), and F, with the extract at 10.0% w/w + UV filters. The antioxidant activity was determined by the DPPH assay and the in vitro efficacy was established by sun protection factor (SPF) measurements (Labsphere UV-2000S). Clinical tests were performed to determine safety (human repeated insult patch test) and to confirm efficacy (photoprotective effectiveness in participants). The results showed a synergistic effect between the sunscreen system and the extract on UVB protection and antioxidant activity. Both samples were considered safe. Formulation F was 20.59% more efficient in protecting skin against UVB radiation, taking approximately 21% more time to induce erythema compared to the extract-free sample. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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15 pages, 2608 KiB

Open AccessArticle

Enhanced Antioxidant and Cytotoxic Potentials of Lipopolysaccharides-Injected Musca domestica Larvae

by Islam El-Garawani, Hesham El-Seedi, Shaden Khalifa, Islam H. El Azab, Marwa Abouhendia and Shaymaa Mahmoud

Pharmaceutics 2020, 12(11), 1111; https://doi.org/10.3390/pharmaceutics12111111 - 19 Nov 2020

Cited by 12 | Viewed by 2241

Abstract

The usage of insects as a sustainable and functional natural products resource is a new promise in complementary and alternative medicine. The present study aimed to investigate the ability of Musca domestica (housefly) larval hemolymph (insect blood) to display the enhanced in vitro [...] Read more.

The usage of insects as a sustainable and functional natural products resource is a new promise in complementary and alternative medicine. The present study aimed to investigate the ability of Musca domestica (housefly) larval hemolymph (insect blood) to display the enhanced in vitro antioxidant and cytotoxic effects. The oxidative stress (OS) was elicited by inducing lipopolysaccharides (LPS) treatment as an exogenous stressor. Determination of superoxide dismutase 1 (SOD1), glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC), and mRNA and protein expressions of SOD1, was investigated as confirmatory markers of oxidative stress induction. Cytotoxicity on cancerous MCF-7 and normal Vero cells were also evaluated using an MTT assay at 24 h post-injection. The injection of LPS induced a significant (p < 0.05) increase in SOD, GSH and TAC, whereas, the MDA was diminished. Hemolymph was collected from normal and treated larvae after 6, 12 and 24 h. The M. domestica superoxide dismutase (MdSOD1) transcripts were significantly (p < 0.05) upregulated 6 and 12 h post-treatment, while a significant downregulation was observed after 24 h. Western blot analysis showed that MdSOD1 was expressed in the hemolymph of the treated larvae with an increase of 1.2 folds at 6 and 12 h and 1.6 folds at 24 h relative to the control group. LPS-treated larval hemolymphs exhibited significant cytotoxicity with respect to the untreated ones against MCF-7 while Vero cells showed no cytotoxicity for both hemolymphs. The DPPH free radical scavenging activity was examined and a significant antioxidant potential potency was observed at 6 h (50% maximal inhibitory concentration (IC₅₀): 63.3 ± 3.51 µg/mL) when compared to the control M. domestica larval hemolymph (IC₅₀: 611.7 ± 10.41 µg/mL). Taken together, M. domestica larval hemolymph exhibited enhanced antioxidant and consequently increased cytotoxic capacities under stressed conditions. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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21 pages, 3002 KiB

Open AccessArticle

Solubility and Stability Enhanced Oral Formulations for the Anti-Infective Corallopyronin A

by Anna K. Krome, Tim Becker, Stefan Kehraus, Andrea Schiefer, Christian Steinebach, Tilman Aden, Stefan J. Frohberger, Álvaro López Mármol, Dnyaneshwar Kapote, Rolf Jansen, Lillibeth Chaverra-Muñoz, Marc P. Hübner, Kenneth Pfarr, Thomas Hesterkamp, Marc Stadler, Michael Gütschow, Gabriele M. König, Achim Hoerauf and Karl G. Wagner

Pharmaceutics 2020, 12(11), 1105; https://doi.org/10.3390/pharmaceutics12111105 - 18 Nov 2020

Cited by 12 | Viewed by 4793

Abstract

Novel-antibiotics are urgently needed to combat an increase in morbidity and mortality due to resistant bacteria. The preclinical candidate corallopyronin A (CorA) is a potent antibiotic against Gram-positive and some Gram-negative pathogens for which a solid oral formulation was needed for further preclinical [...] Read more.

Novel-antibiotics are urgently needed to combat an increase in morbidity and mortality due to resistant bacteria. The preclinical candidate corallopyronin A (CorA) is a potent antibiotic against Gram-positive and some Gram-negative pathogens for which a solid oral formulation was needed for further preclinical testing of the active pharmaceutical ingredient (API). The neat API CorA is poorly water-soluble and instable at room temperature, both crucial characteristics to be addressed and overcome for use as an oral antibiotic. Therefore, amorphous solid dispersion (ASD) was chosen as formulation principle. The formulations were prepared by spray-drying, comprising the water-soluble polymers povidone and copovidone. Stability (high-performance liquid chromatography, Fourier-transform-infrared spectroscopy, differential scanning calorimetry), dissolution (biphasic dissolution), and solubility (biphasic dissolution, Pion’s T3 apparatus) properties were analyzed. Pharmacokinetic evaluations after intravenous and oral administration were conducted in BALB/c mice. The results demonstrated that the ASD formulation principle is a suitable stability- and solubility-enhancing oral formulation strategy for the API CorA to be used in preclinical and clinical trials and as a potential market product. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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17 pages, 2506 KiB

Open AccessArticle

Pequi (Caryocar brasiliense Cambess)-Loaded Nanoemulsion, Orally Delivered, Modulates Inflammation in LPS-Induced Acute Lung Injury in Mice

by Diego de Sá Coutinho, Jader Pires, Hyago Gomes, Adriana Raffin Pohlmann, Sílvia Stanisçuaski Guterres, Patrícia Machado Rodrigues e Silva, Marco Aurelio Martins, Stela Regina Ferrarini and Andressa Bernardi

Pharmaceutics 2020, 12(11), 1075; https://doi.org/10.3390/pharmaceutics12111075 - 11 Nov 2020

Cited by 10 | Viewed by 2470

Abstract

Pequi is a Brazilian fruit used in folk medicine for pulmonary diseases treatment, but its oil presents bioavailability limitations. The use of nanocarriers can overcome this limitation. We developed nanoemulsions containing pequi oil (pequi-NE) and evaluated their effects in a lipopolysaccharide (LPS)-induced lung [...] Read more.

Pequi is a Brazilian fruit used in folk medicine for pulmonary diseases treatment, but its oil presents bioavailability limitations. The use of nanocarriers can overcome this limitation. We developed nanoemulsions containing pequi oil (pequi-NE) and evaluated their effects in a lipopolysaccharide (LPS)-induced lung injury model. Free pequi oil or pequi-NE (20 mg/kg) was orally administered to A/J mice 16 and 4 h prior to intranasal LPS exposure, and the analyses were performed 24 h after LPS provocation. The physicochemical results revealed that pequi-NE comprised particles with mean diameter of 174–223 nm, low polydispersity index (0.11 ± 0.01), zeta potential of −7.13 ± 0.08 mV, and pH of 5.83 ± 0.12. In vivo evaluation showed that free pequi oil pretreatment reduced the influx of inflammatory cells into bronchoalveolar fluid (BALF), while pequi-NE completely abolished leukocyte accumulation. Moreover, pequi-NE, but not free pequi oil, reduced myeloperoxidase (MPO), TNF-α, IL-1β, IL-6, MCP-1, and KC levels. Similar anti-inflammatory effects were observed when LPS-exposed animals were pre-treated with the nanoemulsion containing pequi or oleic acid. These results suggest that the use of nanoemulsions as carriers enhances the anti-inflammatory properties of oleic acid-containing pequi oil. Moreover, pequi’s beneficial effect is likely due its high levels of oleic acid. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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16 pages, 3605 KiB

Open AccessArticle

Coconut Oil Nanoemulsion Loaded with a Statin Hypolipidemic Drug for Management of Burns: Formulation and In Vivo Evaluation

by Khaled M. Hosny, Nabil A. Alhakamy, Amal M. Sindi and Rasha A. Khallaf

Pharmaceutics 2020, 12(11), 1061; https://doi.org/10.3390/pharmaceutics12111061 - 07 Nov 2020

Cited by 31 | Viewed by 3329

Abstract

Burn wound healing is a complex process that involves the repair of injured tissues and the control of infection to diminish the scar formation, pain, and discomfort associated with such injuries. The aim of this research was to formulate and optimize a self-nanoemulsion [...] Read more.

Burn wound healing is a complex process that involves the repair of injured tissues and the control of infection to diminish the scar formation, pain, and discomfort associated with such injuries. The aim of this research was to formulate and optimize a self-nanoemulsion drug delivery system based on the use of coconut oil and loaded with simvastatin. Coconut oil possesses antiinflammatory and antibacterial activity, and simvastatin has interesting properties for promoting the wound-healing process because it increases the production of the vascular endothelial growth factor at the site of injury. The Box–Behnken design was employed for the optimization of the coconut oil–simvastatin self-nanoemulsion drug delivery system. The prepared formulations were characterized according to globular size and their activity in the healing of burn wounds by assessing the mean wound diameter and level of interlukin-6 in experimental animals. Additionally, the antimicrobial activity of the prepared formulations was assessed. The nanoemulsion was considered adequately formed when it had droplets of between 65 and 195 nm. The statistical design proved the important synergistic effect of coconut oil and simvastatin for burn wound management in their synergistic potentiation of wound closure and their anti-inflammatory and antimicrobial effects. The optimum formulation achieved up to a 5.3-fold decrease in the mean burn wound diameter, a 4.25-fold decrease in interleukin-6 levels, and a 6-fold increase in the inhibition zone against Staphylococcus aureus when compared with different control formulations. Therefore, the designed nanoemulsions containing a combination of coconut oil and simvastatin could be considered promising platforms for the treatment of chronic and burn wounds. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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23 pages, 5786 KiB

Open AccessArticle

Development of a Curcumin-Loaded Polymeric Microparticulate Oral Drug Delivery System for Colon Targeting by Quality-by-Design Approach

by Dana Hales, Lucia Ruxandra Tefas, Ioan Tomuță, Cristian Moldovan, Diana Gulei, Raluca Munteanu and Alina Porfire

Pharmaceutics 2020, 12(11), 1027; https://doi.org/10.3390/pharmaceutics12111027 - 27 Oct 2020

Cited by 14 | Viewed by 2375

Abstract

The purpose of this study was to apply the quality-by-design (QbD) approach for the development of colon-targeted curcumin-loaded polymeric microparticles (Col-CUR-MPs). The proportion of the enterosoluble polymer (Eudragit^® FS) in the polymeric matrix, curcumin concentration, and the concentration of the polymer mixture [...] Read more.

The purpose of this study was to apply the quality-by-design (QbD) approach for the development of colon-targeted curcumin-loaded polymeric microparticles (Col-CUR-MPs). The proportion of the enterosoluble polymer (Eudragit^® FS) in the polymeric matrix, curcumin concentration, and the concentration of the polymer mixture (Eudragit^® FS-polycaprolactone) were identified as potential risk factors for the quality of the final product following risk assessment. The influence of these variables on the critical quality attributes (CQAs) of Col-CUR-MPs was investigated. Therefore, a central composite face experimental design was used in order to determine the functional relationships between variables and product CQAs. The obtained regression model and contour plots were used to establish the design space. Finally, the model was validated by preparing two microparticulate formulations, one corresponding to the robust setpoint from within the design space and one outside the established design space, and calculating the percentage bias between the experimental and predicted values. The in vivo study, which was conducted on a fluorescein-loaded formulation that corresponded to the robust setpoint determined by QbD and that contained a mixture of polycaprolactone and Eudragit^® FS (60:40, w/w), confirmed the colon-targeting qualities of this formulation. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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15 pages, 989 KiB

Open AccessArticle

Development of a Solid Formulation Containing a Microemulsion of a Novel Artemisia Extract with Nematocidal Activity for Oral Administration

by Ines Perez-Roman, Filip Kiekens, Damian Cordoba-Diaz, Juan Jose Garcia-Rodriguez and Manuel Cordoba-Diaz

Pharmaceutics 2020, 12(9), 873; https://doi.org/10.3390/pharmaceutics12090873 - 14 Sep 2020

Cited by 7 | Viewed by 3040

Abstract

Background: Intestinal nematode infections are usually treated with benzimidazole drugs, but the emergence of resistance to these drugs has led to an increasing demand of new anthelmintic strategies. A new microemulsion formulation (ME) consisting of an Artemisia absinthium extract with proven nematocidal efficacy [...] Read more.

Background: Intestinal nematode infections are usually treated with benzimidazole drugs, but the emergence of resistance to these drugs has led to an increasing demand of new anthelmintic strategies. A new microemulsion formulation (ME) consisting of an Artemisia absinthium extract with proven nematocidal efficacy was previously developed. The aim of our study is to implement a D-optimal mixture design methodology to increase the amount of a silica material (loaded with this ME) in a tablet formulation, considering its tensile strength and disintegration time. Methods: 16 experiments or combinations of the 6 tablet components (loaded silica, microcrystalline cellulose, polyvinylpyrrolidone, croscarmellose, Syloid^® 244 FP and magnesium stearate) were assessed. Tensile strength and disintegration time models were developed, and an optimization process was carried out. Results: Tensile strength was improved by increasing the polyvinylpyrrolidone content, while croscarmellose decreased the disintegration time. The optimized powder mixture contains 49.7% w/w of the loaded silica material. A compression force of 12 kN was applied to the powder mixture to form tablets with a tensile strength of 2.0 MPa and a disintegration time of 3.8 min. Conclusions: Our results show that D-optimal mixture designs provide a promising approach to formulate liquid-loaded silica materials. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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19 pages, 1831 KiB

Open AccessArticle

Phytol-Loaded Solid Lipid Nanoparticles as a Novel Anticandidal Nanobiotechnological Approach

by Tábata L. C. Lima, Luanda B. F. C. Souza, Lannya C. S. Tavares-Pessoa, Alaine M. dos Santos-Silva, Rômulo S. Cavalcante, Raimundo F. de Araújo-Júnior, Alianda M. Cornélio, Matheus F. Fernandes-Pedrosa, Guilherme Maranhão Chaves and Arnóbio Antônio da Silva-Júnior

Pharmaceutics 2020, 12(9), 871; https://doi.org/10.3390/pharmaceutics12090871 - 13 Sep 2020

Cited by 11 | Viewed by 2785

Abstract

Phytol is a diterpene alcohol and can be found as a product of the metabolism of chlorophyll in plants. This compound has been explored as a potential antimicrobial agent, but it is insoluble in water. In this study, we describe a novel approach [...] Read more.

Phytol is a diterpene alcohol and can be found as a product of the metabolism of chlorophyll in plants. This compound has been explored as a potential antimicrobial agent, but it is insoluble in water. In this study, we describe a novel approach for an interesting anticandidal drug delivery system containing phytol. Different formulations of phytol-loaded solid lipid nanoparticles (SLN) were designed and tested using a natural lipid, 1,3-distearyl-2-oleyl-glycerol (TG1). Different compositions were considered to obtain three formulations with 1:10, 1:5, and 1:3 w/w phytol/TG1 ratios. All the formulations were prepared by emulsification solvent evaporation method and had their physicochemical properties assessed. The biocompatibility assay was performed in the HEK-293 cell line and the antifungal efficacy was demonstrated in different strains of Candida ssp., including different clinical isolates. Spherical and uniform SLN (<300 nm, PdI < 0.2) with phytol-loading efficiency >65% were achieved. Phytol-loaded SLN showed a dose-dependent cytotoxic effect in the HEK-293 cell line. The three tested formulations of phytol-loaded SLN considerably enhanced the minimal inhibitory concentration of phytol against 15 strains of Candida spp. Considering the clinical isolates, the formulations containing the highest phytol/TG1 ratios showed MICs at 100%. Thus, the feasibility and potential of phytol-loaded SLN was demonstrated in vitro, being a promising nanocarrier for phytol delivery from an anticandidal approach. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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16 pages, 4789 KiB

Open AccessArticle

Lipid Nanoparticles for Enhancing the Physicochemical Stability and Topical Skin Delivery of Orobol

by Min-Hwan Kim, Yae-Eun Jeon, Soobeen Kang, Jae-Young Lee, Ki Won Lee, Ki-Taek Kim and Dae-Duk Kim

Pharmaceutics 2020, 12(9), 845; https://doi.org/10.3390/pharmaceutics12090845 - 03 Sep 2020

Cited by 18 | Viewed by 3089

Abstract

Orobol is one of the major soy isoflavones, and has been reported to have various pharmacological activities, including an anti-skin-aging effect. However, since it has low solubility in water and physicochemical instability, the formulation of orobol for delivery into the dermal layer of [...] Read more.

Orobol is one of the major soy isoflavones, and has been reported to have various pharmacological activities, including an anti-skin-aging effect. However, since it has low solubility in water and physicochemical instability, the formulation of orobol for delivery into the dermal layer of the skin could be challenging. The objective of this study was to prepare lipid nanoparticles formulations of orobol to enhance its stability as well as its deposition into the skin. Formulations of orobol-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were characterized in terms of their mean particle size, entrapment efficiency, and morphology. The nano-sized spherical NLCs formulations maintained the stability of orobol for up to 28 days. Moreover, the NLCs formulation significantly increased the in vitro deposition of orobol into both Strat-M membranes and human cadaver skin compared with the other formulations. Additionally, the NLCs formulation did not cause significant skin irritation in clinical study. These results demonstrate that a shea butter-based NLC formulation could be a promising and safe carrier system for improving the stability of orobol and enhancing its topical skin delivery. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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18 pages, 2235 KiB

Open AccessArticle

Antimicrobial Essential Oil Formulation: Chitosan Coated Nanoemulsions for Nose to Brain Delivery

by Federica Rinaldi, Alessandra Oliva, Manuela Sabatino, Anna Imbriano, Patrizia N. Hanieh, Stefania Garzoli, Claudio M. Mastroianni, Massimiliano De Angelis, Maria Claudia Miele, Marcela Arnaut, Federica Di Timoteo, Carlotta Marianecci, Rino Ragno and Maria Carafa

Pharmaceutics 2020, 12(7), 678; https://doi.org/10.3390/pharmaceutics12070678 - 17 Jul 2020

Cited by 30 | Viewed by 3352

Abstract

Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose [...] Read more.

Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose to the brain administration route, is a non-invasive alternative for a quick onset of action, and enables the transport of numerous medicinal agents straight to the brain thus workarounding the BBB through the highly vascularized olfactory region. In this report, Thymus vulgaris and Syzygium aromaticum essential oils (EOs) were selected to be included in chitosan coated nanoemulsions (NEs). The EOs were firstly analyzed to determine their chemical composition, then used to prepare NEs, that were deeply characterized in order to evaluate their use in intranasal administration. An in vitro evaluation against a collection of clinical isolated bacterial strains was carried out for both free and nanoemulsioned EOs. Chitosan coated NEs showed to be a potential and effective intranasal formulation against multi-drug resistant Gram-negative bacteria such as methicillin-susceptible Staphylococcus aureus and multi-drug resistant Gram-negative microorganisms including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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14 pages, 2562 KiB

Open AccessArticle

Hura crepitans L. Extract: Phytochemical Characterization, Antioxidant Activity, and Nanoformulation

by Antonio Vassallo, Maria Francesca Armentano, Rocchina Miglionico, Carla Caddeo, Claudia Chirollo, Maria Josefina Gualtieri, Angela Ostuni, Faustino Bisaccia, Immacolata Faraone and Luigi Milella

Pharmaceutics 2020, 12(6), 553; https://doi.org/10.3390/pharmaceutics12060553 - 15 Jun 2020

Cited by 19 | Viewed by 3436

Abstract

The purpose of this study was to improve the knowledge on Hura crepitans L., a plant belonging to the Euphorbiaceae family that, on the one hand, is known to be toxic, but on the other, is a source of polyphenols with health-promoting effects. [...] Read more.

The purpose of this study was to improve the knowledge on Hura crepitans L., a plant belonging to the Euphorbiaceae family that, on the one hand, is known to be toxic, but on the other, is a source of polyphenols with health-promoting effects. Different green extraction methods were applied, varying solvent, temperature, and duration of extraction, which can influence the phytochemical profile and biological activity of plant extracts, and the extracts were fully characterized. Aqueous extracts exhibited a superior antioxidant activity, as indicated by different spectrophotometric tests, and were cytoprotective to HepG2 cells used as model cells. Liquid chromatography–mass spectrometry analyses were performed to identify the secondary metabolites involved in these effects and demonstrated that solvent, duration, and temperature indeed influenced the extraction of polyphenols. Furthermore, the most promising extract, in terms of antioxidant potential, was incorporated into liposomes with the aim of promoting cell interaction and enhancing the antioxidant activity. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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22 pages, 4440 KiB

Open AccessArticle

Encapsulation of Oleuropein in Nanostructured Lipid Carriers: Biocompatibility and Antioxidant Efficacy in Lung Epithelial Cells

by Amaia Huguet-Casquero, Maria Moreno-Sastre, Tania Belén López-Méndez, Eusebio Gainza and Jose Luis Pedraz

Pharmaceutics 2020, 12(5), 429; https://doi.org/10.3390/pharmaceutics12050429 - 06 May 2020

Cited by 40 | Viewed by 3892

Abstract

Oxidative damage has been linked to a number of diseases. Oleuropein (OLE), a natural occurring polyphenol from olive leaves (Olea europaea L.), is known to be a potent antioxidant compound with inherent instability and compromised bioavailability. Therefore, in this work, nanostructured [...] Read more.

Oxidative damage has been linked to a number of diseases. Oleuropein (OLE), a natural occurring polyphenol from olive leaves (Olea europaea L.), is known to be a potent antioxidant compound with inherent instability and compromised bioavailability. Therefore, in this work, nanostructured lipid carriers (NLCs) were proposed for OLE encapsulation to protect and improve its antioxidant efficacy. The lipid matrix, composed of olive oil and Precirol, was optimized prior to OLE encapsulation. The characterization of the optimized oleuropein-loaded NLCs (NLC-OLE) showed a mean size of 150 nm, a zeta potential of −21 mV, an encapsulation efficiency of 99.12%, sustained release profile, and improved radical scavenging activity. The cellular in vitro assays demonstrated the biocompatibility of the NLCs, which were found to improve and maintain OLE antioxidant efficacy in the A549 and CuFi-1 lung epithelial cell lines, respectively. Overall, these findings suggest a promising potential of NLC-OLE to further design a pulmonary formulation for OLE delivery in lung epithelia. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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25 pages, 6699 KiB

Open AccessArticle

Encapsulation of Black Seed Oil in Alginate Beads as a pH-Sensitive Carrier for Intestine-Targeted Drug Delivery: In Vitro, In Vivo and Ex Vivo Study

by Abul Kalam Azad, Sinan Mohammed Abdullah Al-Mahmood, Bappaditya Chatterjee, Wan Mohd Azizi Wan Sulaiman, Tarek Mohamed Elsayed and Abd Almonem Doolaanea

Pharmaceutics 2020, 12(3), 219; https://doi.org/10.3390/pharmaceutics12030219 - 02 Mar 2020

Cited by 57 | Viewed by 7178

Abstract

Black seed oil (BSO) has been used for various therapeutic purposes around the world since ancient eras. It is one of the most prominent oils used in nutraceutical formulations and daily consumption for its significant therapeutic value is common phenomena. The main aim [...] Read more.

Black seed oil (BSO) has been used for various therapeutic purposes around the world since ancient eras. It is one of the most prominent oils used in nutraceutical formulations and daily consumption for its significant therapeutic value is common phenomena. The main aim of this study was to develop alginate-BSO beads as a controlled release system designed to control drug release in the gastrointestinal tract (GIT). Electrospray technology facilitates formulation of small and uniform beads with higher diffusion and swelling rates resulting in process performance improvement. The effect of different formulation and process variables was evaluated on the internal and external bead morphology, size, shape, encapsulation efficiency, swelling rate, in vitro drug release, release mechanism, ex vivo mucoadhesive strength and gastrointestinal tract qualitative and quantitative distribution. All the formulated beads showed small sizes of 0.58 ± 0.01 mm (F8) and spherical shape of 0.03 ± 0.00 mm. The coefficient of weight variation (%) ranged from 1.37 (F8) to 3.93 (F5) ng. All formulations (F1–F9) were studied in vitro for release characteristics and swelling behaviour, then the release data were fitted to various equations to determine the exponent (ns), swelling kinetic constant (ks), swelling rate (%/h), correlation coefficient (r²) and release kinetic mechanism. The oil encapsulation efficiency was almost complete at 90.13% ± 0.93% in dried beads. The maximum bead swelling rate showed 982.23 (F8, r² = 0.996) in pH 6.8 and the drug release exceeded 90% in simulated gastrointestinal fluid (pH 6.8). Moreover, the beads were well distributed throughout various parts of the intestine. This designed formulation could possibly be advantageous in terms of increased bioavailability and targeted drug delivery to the intestine region and thus may find applications in some diseases like irritable bowel syndrome. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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13 pages, 3764 KiB

Open AccessArticle

Novel Carboxylated Chitosan-Based Triptolide Conjugate for the Treatment of Rheumatoid Arthritis

by Lan Zhang, Min Yan, Kun Chen, Qikang Tian, Junying Song, Zijuan Zhang, Zhishen Xie, Yong Yuan, Yaquan Jia, Xin Zhu, Zhenqiang Zhang, Xiangxiang Wu and Huahui Zeng

Pharmaceutics 2020, 12(3), 202; https://doi.org/10.3390/pharmaceutics12030202 - 26 Feb 2020

Cited by 15 | Viewed by 2356

Abstract

A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (>5 mg/mL). Results of in vitro experiments showed that [...] Read more.

A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (>5 mg/mL). Results of in vitro experiments showed that TP-CMCS could relieve TP-induced inhibition on RAW264.7 cells and apoptosis, respectively. Compared with the TP group, TP-CMCS could effectively alleviate the toxicity injury of TP and decreased the mortality rate of the mice (p < 0.05). TP-CMCS did not cause much damage to the liver (AST and ALT) and kidney (BUN and CRE) (p < 0.05). After administration, the levels of IL-6, IL-1β, and TNF-α decreased, and the arthritis detumescence percentages increased significantly, and the bony erosion degree was distinctly decreased in the TP-CMCS groups and TP group. Our results suggested that TP-CMCS was a useful carrier for the treatment of RA, which enhanced aqueous solubility of free TP and reduced drug toxicity in vitro and in vivo. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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0 pages, 4290 KiB

Open AccessArticle

RETRACTED: Omega-3 Self-Nanoemulsion Role in Gastroprotection against Indomethacin-Induced Gastric Injury in Rats

by Osama A. A. Ahmed, Usama A. Fahmy, Rana Bakhaidar, Mohamed A. El-Moselhy, Solomon Z. Okbazghi, Al-Shaimaa F. Ahmed, Asmaa S. A. Hammad and Nabil A. Alhakamy

Pharmaceutics 2020, 12(2), 140; https://doi.org/10.3390/pharmaceutics12020140 - 07 Feb 2020

Cited by 19 | Viewed by 7142 | Retraction

Abstract

Peptic ulcer disease is an injury of the alimentary tract that leads to a mucosal defect reaching the submucosa. This study aimed to formulate and optimize omega-3 oil as a self-nanoemulsifying drug delivery system (SNEDDS) to achieve oil dispersion in the nano-range in [...] Read more.

Peptic ulcer disease is an injury of the alimentary tract that leads to a mucosal defect reaching the submucosa. This study aimed to formulate and optimize omega-3 oil as a self-nanoemulsifying drug delivery system (SNEDDS) to achieve oil dispersion in the nano-range in the stomach to augment omega-3 oil gastric ulcer protection efficacy. Three SNEDDS components were selected as the design factors: the concentrations of the oil omega-3 (X1, 10–30%), the surfactant tween 20 and Kolliphor mixture (X2, 20–40%), and the cosurfactant transcutol (X3, 40–60%). The mixture experimental design proposed twenty-three formulations with varying omega-3 SNEDDS formulation component percentages. The optimized omega-3 SNEDDS formula was investigated for gastric ulcer protective effects by evaluating the ulcer index and by the determination of gastric mucosa oxidative stress parameters. Results revealed that optimized omega-3-SNEDDS achieved significant improvement in the gastric ulcer index in comparison with pure omega-3 oil. Histopathological findings confirmed the protective effect of the formulated optimized omega-3 SNEDDS in comparison with omega-3 oil. These findings suggest that formulation of omega-3 in the form of a SNEDDS would be more effective in gastric ulcer protection than the administration of omega-3 as a crude oil. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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Review

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34 pages, 1024 KiB

Open AccessReview

Nanoparticles Formulations of Artemisinin and Derivatives as Potential Therapeutics for the Treatment of Cancer, Leishmaniasis and Malaria

by Sibusiso Alven and Blessing Atim Aderibigbe

Pharmaceutics 2020, 12(8), 748; https://doi.org/10.3390/pharmaceutics12080748 - 09 Aug 2020

Cited by 25 | Viewed by 4955

Abstract

Cancer, malaria, and leishmaniasis remain the deadly diseases around the world although several strategies of treatment have been developed. However, most of the drugs used to treat the aforementioned diseases suffer from several pharmacological limitations such as poor pharmacokinetics, toxicity, drug resistance, poor [...] Read more.

Cancer, malaria, and leishmaniasis remain the deadly diseases around the world although several strategies of treatment have been developed. However, most of the drugs used to treat the aforementioned diseases suffer from several pharmacological limitations such as poor pharmacokinetics, toxicity, drug resistance, poor bioavailability and water solubility. Artemisinin and its derivatives are antimalarial drugs. However, they also exhibit anticancer and antileishmanial activity. They have been evaluated as potential anticancer and antileishmanial drugs but their use is also limited by their poor water solubility and poor bioavailability. To overcome the aforementioned limitations associated with artemisinin and its derivatives used for the treatment of these diseases, they have been incorporated into nanoparticles. Several researchers incorporated this class of drugs into nanoparticles resulting in enhanced therapeutic outcomes. Their potential efficacy for the treatment of parasitic infections such as malaria and leishmaniasis and chronic diseases such as cancer has been reported. This review article will be focused on the nanoparticles formulations of artemisinin and derivatives for the treatment of cancer, malaria, and leishmaniasis and the biological outcomes (in vitro and in vivo). Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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20 pages, 2701 KiB

Open AccessReview

3D Printed Drug Delivery Systems Based on Natural Products

by Ángela Aguilar-de-Leyva, Vicente Linares, Marta Casas and Isidoro Caraballo

Pharmaceutics 2020, 12(7), 620; https://doi.org/10.3390/pharmaceutics12070620 - 03 Jul 2020

Cited by 46 | Viewed by 6508

Abstract

In the last few years, the employment of 3D printing technologies in the manufacture of drug delivery systems has increased, due to the advantages that they offer for personalized medicine. Thus, the possibility of producing sophisticated and tailor-made structures loaded with drugs intended [...] Read more.

In the last few years, the employment of 3D printing technologies in the manufacture of drug delivery systems has increased, due to the advantages that they offer for personalized medicine. Thus, the possibility of producing sophisticated and tailor-made structures loaded with drugs intended for tissue engineering and optimizing the drug dose is particularly interesting in the case of pediatric and geriatric population. Natural products provide a wide range of advantages for their application as pharmaceutical excipients, as well as in scaffolds purposed for tissue engineering prepared by 3D printing technologies. The ability of biopolymers to form hydrogels is exploited in pressure assisted microsyringe and inkjet techniques, resulting in suitable porous matrices for the printing of living cells, as well as thermolabile drugs. In this review, we analyze the 3D printing technologies employed for the preparation of drug delivery systems based on natural products. Moreover, the 3D printed drug delivery systems containing natural products are described, highlighting the advantages offered by these types of excipients. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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31 pages, 2907 KiB

Open AccessReview

New Trends in Bio-Based Aerogels

by Loredana Elena Nita, Alina Ghilan, Alina Gabriela Rusu, Iordana Neamtu and Aurica P. Chiriac

Pharmaceutics 2020, 12(5), 449; https://doi.org/10.3390/pharmaceutics12050449 - 13 May 2020

Cited by 107 | Viewed by 7845

Abstract

(1) Background: The fascinating properties of currently synthesized aerogels associated with the flexible approach of sol-gel chemistry play an important role in the emergence of special biomedical applications. Although it is increasingly known and mentioned, the potential of aerogels in the medical field [...] Read more.

(1) Background: The fascinating properties of currently synthesized aerogels associated with the flexible approach of sol-gel chemistry play an important role in the emergence of special biomedical applications. Although it is increasingly known and mentioned, the potential of aerogels in the medical field is not sufficiently explored. Interest in aerogels has increased greatly in recent decades due to their special properties, such as high surface area, excellent thermal and acoustic properties, low density and thermal conductivity, high porosity, flame resistance and humidity, and low refractive index and dielectric constant. On the other hand, high manufacturing costs and poor mechanical strength limit the growth of the market. (2) Results: In this paper, we analyze more than 180 articles from recent literature studies focused on the dynamics of aerogels research to summarize the technologies used in manufacturing and the properties of materials based on natural polymers from renewable sources. Biomedical applications of these bio-based materials are also introduced. (3) Conclusions: Due to their complementary functionalities (bioactivity, biocompatibility, biodegradability, and unique chemistry), bio-based materials provide a vast capability for utilization in the field of interdisciplinary and multidisciplinary scientific research. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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25 pages, 3155 KiB

Open AccessReview

Nano- and Microcarriers as Drug Delivery Systems for Usnic Acid: Review of Literature

by Ana Zugic, Vanja Tadic and Snezana Savic

Pharmaceutics 2020, 12(2), 156; https://doi.org/10.3390/pharmaceutics12020156 - 15 Feb 2020

Cited by 23 | Viewed by 3525

Abstract

Usnic acid is one of the most investigated lichen secondary metabolites, with several proven biological properties with potential medical relevance. However, its unfavorable physico-chemical properties, as well as observed hepatotoxicity, have discouraged wide-range utilization of usnic acid as a promising therapeutic agent. In [...] Read more.

Usnic acid is one of the most investigated lichen secondary metabolites, with several proven biological properties with potential medical relevance. However, its unfavorable physico-chemical properties, as well as observed hepatotoxicity, have discouraged wide-range utilization of usnic acid as a promising therapeutic agent. In accordance with the growing research interest in the development of nanotechnology, especially in the arena of preparations based on natural sources of medicinal compounds, usnic acid incorporated into nano- and microsized colloidal carriers has been a subject of a large number of publications. Therefore, this review discusses the overall results of the studies dealing with usnic acid encapsulated into lipid-based, polymeric and nonorganic micro- and/or nanocarriers, as potential drug delivery systems for this natural compound, in an attempt to introduce its usage as a potential antitumor, antimicrobial, wound-healing, antioxidative and anti-inflammatory drug. Full article

(This article belongs to the Special Issue Natural Products in Drug Delivery Systems)

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