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21 pages, 2100 KiB

Open AccessArticle

Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

by Tatyana Kovshova, Nadezhda Osipova, Anna Alekseeva, Julia Malinovskaya, Alexey Belov, Andrey Budko, Galina Pavlova, Olga Maksimenko, Shakti Nagpal, Svenja Braner, Harshvardhan Modh, Vadim Balabanyan, Matthias G. Wacker and Svetlana Gelperina

Molecules 2021, 26(4), 831; https://doi.org/10.3390/molecules26040831 - 05 Feb 2021

Cited by 19 | Viewed by 4558

Abstract

Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different [...] Read more.

Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC_0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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18 pages, 3047 KiB

Open AccessArticle

Nanomaterial Lipid-Based Carrier for Non-Invasive Capsaicin Delivery; Manufacturing Scale-Up and Human Irritation Assessment

by Phunsuk Anantaworasakul, Songyot Anuchapreeda, Songwut Yotsawimonwat, Ornchuma Naksuriya, Suree Lekawanvijit, Napatra Tovanabutra, Pimporn Anantaworasakul, Wajee Wattanasri, Narinthorn Buranapreecha and Chadarat Ampasavate

Molecules 2020, 25(23), 5575; https://doi.org/10.3390/molecules25235575 - 27 Nov 2020

Cited by 9 | Viewed by 2456

Abstract

Capsaicin is an active compound in chili peppers (Capsicum chinense) that has been approved for chronic pain treatment. The topical application of high-strength capsaicin has been proven to reduce pain; however, skin irritation is a major drawback. The aim of this [...] Read more.

Capsaicin is an active compound in chili peppers (Capsicum chinense) that has been approved for chronic pain treatment. The topical application of high-strength capsaicin has been proven to reduce pain; however, skin irritation is a major drawback. The aim of this study was to investigate an appropriate and scalable technique for preparing nanostructured lipid carriers (NLCs) containing 0.25% capsaicin from capsicum oleoresin (NLC_C) and to evaluate the irritation of human skin by chili-extract-loaded NLCs incorporated in a gel formulation (Gel NLC_C). High-shear homogenization with high intensity (10,000 rpm) was selected to create uniform nanoparticles with a size range from 106 to 156 nm. Both the NLC_C and Gel NLC_C formulations expressed greater physical and chemical stabilities than the free chili formulation. Release and porcine biopsy studies revealed the sustained drug release and significant permeation of the NLCs through the outer skin layer, distributing in the dermis better than the free compounds. Finally, the alleviation of irritation and the decrease in uncomfortable feelings following the application of the Gel NLC_C formulation were compared to the effects from a chili gel and a commercial product in thirty healthy volunteers. The chili-extract-loaded NLCs were shown to be applicable for the transdermal delivery of capsaicin whilst minimizing skin irritation, the major noncompliance cause of patients. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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14 pages, 3082 KiB

Open AccessArticle

In Vivo Effect of Resveratrol-Loaded Solid Lipid Nanoparticles to Relieve Physical Fatigue for Sports Nutrition Supplements

by Lili Qin, Tianfeng Lu, Yao Qin, Yiwei He, Ningxin Cui, Ai Du and Jingyu Sun

Molecules 2020, 25(22), 5302; https://doi.org/10.3390/molecules25225302 - 13 Nov 2020

Cited by 14 | Viewed by 2463

Abstract

Resveratrol (RSV) is a natural flavonoid polyphenol compound extracted from the plants which shows various biological activities. However, the clinical application of RSV is limited by its poor aqueous solubility, rapid metabolism and poor bioavailability. In this study, resveratrol-loaded solid lipid nanoparticles (RSV- [...] Read more.

Resveratrol (RSV) is a natural flavonoid polyphenol compound extracted from the plants which shows various biological activities. However, the clinical application of RSV is limited by its poor aqueous solubility, rapid metabolism and poor bioavailability. In this study, resveratrol-loaded solid lipid nanoparticles (RSV- SLNs) was design as a nano-antioxidant against the physical fatigue. The resultant RSV-SLNs were characterized by photon correlation spectroscopy (PCS), transmission electron micrographs (TEM), zeta potential, differential scanning calorimetry (DSC) and Raman spectroscopy pattern. Furthermore, the in vivo anti-fatigue effect assays showed that RSV-SLNs prolonged the mice exhausted time and running distance. The biochemical parameters of blood related to fatigue suggested that RSV-SLNs have potential applications to improve the antioxidant defense of the mice after extensive exercise and confer anti-fatigue capability. Furthermore, the molecular mechanisms of antioxidant by RSV-SLNs supplementation was investigated through the analysis of silent information regulator 2 homolog 1 (SIRT1) protein expression, which demonstrated that it could downregulate the expression of SIRT1 and increase autophagy markers, microtubule-associated protein 1 light chain 3-II (LC3-II) and sequestosome-1 (SQSTM1/p62). These results reveal that the RSV-SLNs may have great potential used as a novel anti-fatigue sports nutritional supplement. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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14 pages, 3092 KiB

Open AccessArticle

An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats

by Hye-Jin Lee, Moses Jeong, Young-Guk Na, Sung-Jin Kim, Hong-Ki Lee and Cheong-Weon Cho

Molecules 2020, 25(20), 4610; https://doi.org/10.3390/molecules25204610 - 10 Oct 2020

Cited by 37 | Viewed by 3549

Abstract

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter [...] Read more.

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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18 pages, 3760 KiB

Open AccessArticle

Curcumin Containing PEGylated Solid Lipid Nanoparticles for Systemic Administration: A Preliminary Study

by Debora Santonocito, Maria Grazia Sarpietro, Claudia Carbone, Annamaria Panico, Agata Campisi, Edy Angela Siciliano, Giovanni Sposito, Francesco Castelli and Carmelo Puglia

Molecules 2020, 25(13), 2991; https://doi.org/10.3390/molecules25132991 - 30 Jun 2020

Cited by 25 | Viewed by 3423

Abstract

Curcumin (CUR) has a wide range of pharmacological properties, including anti-inflammatory and antioxidant activities, and it can be considered a good candidate for the potential treatment of central nervous system (CNS) pathologies, although its use in clinical practice is compromised due to its [...] Read more.

Curcumin (CUR) has a wide range of pharmacological properties, including anti-inflammatory and antioxidant activities, and it can be considered a good candidate for the potential treatment of central nervous system (CNS) pathologies, although its use in clinical practice is compromised due to its high lipophilicity. Solid lipid nanoparticles (SLNs) are well-known nanocarriers representing a consolidated approach for the delivery of lipophilic compounds, but their systemic use is limited due their short half-life. The formulation of stealth SLNs (pSLNs) could be a valid strategy to overcome this limit. Curcumin-loaded-pSLNs were prepared by the solvent evaporation method. Formulation was characterized for their mean size, zeta potential, size distribution, and morphology. Drug antioxidant activity was evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay. Finally, the obtained formulations were analyzed in terms of long-term stability. Curcumin-loaded-pSLNs showed good technological parameters with a mean particle size below 200 nm, as confirmed by TEM images, and a zeta potential value around −30 mV, predicting good long-term stability. Differential Scanning Calorimetry (DSC) analysis confirmed that PEG micelles interacted with the SLN surface; this suggests the location of the PEG on the pSLN surface. Therefore, these preliminary studies suggest that the produced formulation could be regarded as a promising carrier for the systemic administration. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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24 pages, 3014 KiB

Open AccessArticle

Physicochemical Properties and Liposomal Formulations of Hydrolysate Fractions of Four Sea Cucumbers (Holothuroidea: Echinodermata) from the Northwestern Algerian Coast

by Asmaa Mecheta, Amine Hanachi, Carole Jeandel, Elmira Arab-Tehrany, Arnaud Bianchi, Emilie Velot, Karim Mezali and Michel Linder

Molecules 2020, 25(13), 2972; https://doi.org/10.3390/molecules25132972 - 28 Jun 2020

Cited by 6 | Viewed by 3055

Abstract

To promote the nutritional and pharmacological values of four sea cucumber species (Holothuria poli, H. tubulosa, H. arguinensis, and H. sanctori), harvested from the Algerian coast, we aimed to study their proximate composition, fatty acid profile and angiotensin-converting enzyme (ACE) [...] Read more.

To promote the nutritional and pharmacological values of four sea cucumber species (Holothuria poli, H. tubulosa, H. arguinensis, and H. sanctori), harvested from the Algerian coast, we aimed to study their proximate composition, fatty acid profile and angiotensin-converting enzyme (ACE) inhibitory activity. Their phospholipids were also used to elaborate nanoliposomes and to encapsulate peptides obtained from the same source. After the physico-chemical characterization of nanoliposomes and peptides, in vitro analyses were realized. The four holothurian species showed a high amount of protein (49.26–69.34%), and an impressive lipid profile of 27 fatty acids, mainly composed of polar fatty acids (91.16–93.85%), with a high polyunsaturated fatty acids (PUFA) content (50.90–71.80%), particularly eicosapentaenoic acid (EPA) (5.07–8.76%) and docosahexaenoic acid (DHA) (4.86–7.25%). A high phospholipids amount was also found (55.20–69.85%), mainly composed of phosphatidylcholine (PC) (51.48–58.56%). Their peptide fractions exhibited a high ACE inhibitory activity (IC₅₀ 0.30 to 0.51 mg/mL). The results also showed that the nanoliposomes do not induce cytotoxicity and cell death in human MSCs and no perturbation of proliferation for all the times and the tested concentrations, as well as the combined nanoliposomes and hydrolysates (HTS) at a concentration of 0.1 mg/mL. All four sea cucumbers show potential as a new source for omega-3, omega-6, and bioactive peptides. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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13 pages, 1187 KiB

Open AccessArticle

Glycyrrhetinic Acid Liposomes and Hyalurosomes on Spanish Broom, Flax, and Hemp Dressings to Heal Skin Wounds

by Angela Abruzzo, Concettina Cappadone, Giovanna Farruggia, Barbara Luppi, Federica Bigucci and Teresa Cerchiara

Molecules 2020, 25(11), 2558; https://doi.org/10.3390/molecules25112558 - 31 May 2020

Cited by 19 | Viewed by 2922

Abstract

The focus of this work was to prepare Spanish Broom, flax, and hemp dressings impregnated with glycyrrhetinic acid (GA) liposomes or hyalurosomes to promote the healing process and protect the skin wounds. Vesicles were prepared by the film hydration method and characterized in [...] Read more.

The focus of this work was to prepare Spanish Broom, flax, and hemp dressings impregnated with glycyrrhetinic acid (GA) liposomes or hyalurosomes to promote the healing process and protect the skin wounds. Vesicles were prepared by the film hydration method and characterized in terms of size, particle size distribution, ζ potential, encapsulation efficiency, in vitro release, and biocompatibility on 3T3 fibroblasts. Loaded liposomes and hyalurosomes showed nanometric size (355 ± 19 nm and 424 ± 32 nm, respectively), good size distribution (lower than 0.3), and appropriate encapsulation efficiency (58.62 ± 3.25% and 59.22 ± 8.18%, respectively). Hyalurosomes showed good stability during the storage period, which can be correlated to the negative ζ potential, and allowed a fast and complete release of GA. Preliminary biological studies revealed that both kinds of loaded vesicles were not cytotoxic and that hyalurosomes could exert a slight stimulating effect on fibroblast proliferation. Finally, in vitro release studies from the different dressings impregnated with the loaded vesicles demonstrated that a high amount of GA could be reached at the wound site after 60 min from application. In conclusion, the results suggested that the developed dressings, especially those impregnated with hyalurosomes, can be efficiently used to promote the healing process. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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24 pages, 5872 KiB

Open AccessArticle

Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS) for Combined Oral Delivery of Curcumin and Piperine

by Mohsin Kazi, Ahmad A. Shahba, Saad Alrashoud, Majed Alwadei, Abdelrahman Y. Sherif and Fars K. Alanazi

Molecules 2020, 25(7), 1703; https://doi.org/10.3390/molecules25071703 - 08 Apr 2020

Cited by 51 | Viewed by 6000

Abstract

Background: Bioactive oils of natural origin have gained huge interests from health care professionals and patients. Objective: To design a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS) comprising curcumin (CUR) and piperine (PP) by incorporating bioactive natural oils in the formulation. Methods [...] Read more.

Background: Bioactive oils of natural origin have gained huge interests from health care professionals and patients. Objective: To design a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS) comprising curcumin (CUR) and piperine (PP) by incorporating bioactive natural oils in the formulation. Methods: The self-emulsifying properties of apricot, avocado, black seed and Zanthoxylum rhetsa seed oils were screened within various SNEDDS formulations. Each liquid SNEDDS formulation was loaded with both CUR and PP. The optimal liquid SNEDDS were solidified using Aeroperl^® and Neusilin^® at 1:1 w/w ratio. Liquid and solid SNEDDS were characterized by droplet size analysis, equilibrium solubility, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. In-vitro dissolution studies were performed to evaluate the efficiency of CUR and PP release from solid Bio-SNEDDS. Results: The liquid SNEDDS comprised of black seed oil exhibited excellent self-emulsification performance, low droplet size along with transparent appearance. The inclusion of the cosolvent Transcutol P improved the solubilization capacity of both CUR and PP. The liquid SNEDDS were efficiently solidified using the two adsorbents and presented the drugs within amorphous state. In particular, SNEDDS comprised of black seed oil/Imwitor988/Transcutol P/Cremophor RH40 (20/20/10/50) and when solidified with Neusilin showed enhanced CUR and PP release (up to 60% and 77%, respectively). In addition, this formulation efficiently delivers the highly bioactive black seed oil to the patient. Conclusions: The optimized Bio-SNEDDS comprising black seed oil showed outstanding self-emulsification characteristics along with enhanced CUR/PP dissolution upon solidification. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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15 pages, 1531 KiB

Open AccessArticle

Ellagic Acid Containing Nanostructured Lipid Carriers for Topical Application: A Preliminary Study

by Supandeep Singh Hallan, Maddalena Sguizzato, Gabriella Pavoni, Anna Baldisserotto, Markus Drechsler, Paolo Mariani, Elisabetta Esposito and Rita Cortesi

Molecules 2020, 25(6), 1449; https://doi.org/10.3390/molecules25061449 - 23 Mar 2020

Cited by 31 | Viewed by 5174

Abstract

Ellagic acid (EA) is a potent antioxidant substance of natural origin characterized by poor biopharmaceutical properties and low solubility in water that limit its use. The aim of the present study was to develop lipid-based nanoparticle formulations able to encapsulate EA for dermal [...] Read more.

Ellagic acid (EA) is a potent antioxidant substance of natural origin characterized by poor biopharmaceutical properties and low solubility in water that limit its use. The aim of the present study was to develop lipid-based nanoparticle formulations able to encapsulate EA for dermal delivery. The EA-loaded nanoparticles were prepared using two different lipid compositions, namely tristearin/tricaprylin (NLC-EA1) and tristearin/labrasol (NLC-EA2). The influence of formulations on size, entrapment efficiency, and stability of EA-loaded nanoparticles was investigated. Cryo-TEM and small-angle X-ray scattering (SAXS) analyses showed that no morphological differences are evident among all the types of loaded and unloaded nanostructured lipid carriers (NLCs). The macroscopic aspect of both NLC-EA1 and NLC-EA2 did not change with time. No difference in size was appreciable between empty and drug-containing NLC, thus the nanoparticle diameter was not affected by the presence of EA and in general no variations of the diameters occurred during this time. The entrapment efficiency of both EA-loaded nanoparticles was almost quantitative. In addition, NLC-EA1 maintained EA stability for almost two months, while NLC-EA2 up to 40 days. FRAP (Ferric reducing ability of plasma) assay showed an antioxidant activity around 60% for both the loaded NLC, as compared to the solution. Although both types of NLC are characterized by some toxicity on HaCaT cells, NLC-EA1 are less cytotoxic than NLC-EA2. Taken together these results demonstrated that the inclusion of EA within NLC could improve the water solubility, allowing for a reduction of the dosage. Moreover, both types of NLC-EA maintained a high antioxidant effect and low toxicity. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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12 pages, 2195 KiB

Open AccessArticle

A Liposomal Formulation for Improving Solubility and Oral Bioavailability of Nifedipine

by Ye Bi, Bingcong Lv, Lianlian Li, Robert J. Lee, Jing Xie, Zhidong Qiu and Lesheng Teng

Molecules 2020, 25(2), 338; https://doi.org/10.3390/molecules25020338 - 14 Jan 2020

Cited by 19 | Viewed by 3557

Abstract

Proliposomes were used to improve the solubility and oral bioavailability of nifedipine. Nifedipine proliposomes were prepared by methanol injection-spray drying method. The response surface method was used to optimize formulation to enhance the encapsulation efficiency (EE%) of nifedipine. The particle size of nifedipine [...] Read more.

Proliposomes were used to improve the solubility and oral bioavailability of nifedipine. Nifedipine proliposomes were prepared by methanol injection-spray drying method. The response surface method was used to optimize formulation to enhance the encapsulation efficiency (EE%) of nifedipine. The particle size of nifedipine proliposomes after rehydration was 114 nm. Surface morphology of nifedipine proliposomes was observed by a scanning electron microscope (SEM) and interaction of formulation ingredients was assessed by differential scanning calorimetry (DSC). The solubility of nifedipine is improved 24.8 times after forming proliposomes. In vitro release experiment, nifedipine proliposomes had a control release effect, especially in simulated gastric fluid. In vivo, nifedipine proliposomes significantly improved the bioavailability of nifedipine. The area under the concentration-time curve (AUC_0–∞) of nifedipine proliposomes was about 10 times than nifedipine after oral administration. The elimination half-life (T_1/2β) of nifedipine was increased from 1.6 h to 6.6 h. In conclusion, proliposomes was a promising system to deliver nifedipine through oral route and warranted further investigation. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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18 pages, 6113 KiB

Open AccessArticle

Preparation and Evaluation of Carbamazepine Solid Lipid Nanoparticle for Alleviating Seizure Activity in Pentylenetetrazole-Kindled Mice

by Mona Qushawy, Kousalya Prabahar, Mohammed Abd-Alhaseeb, Shady Swidan and Ali Nasr

Molecules 2019, 24(21), 3971; https://doi.org/10.3390/molecules24213971 - 02 Nov 2019

Cited by 22 | Viewed by 3803

Abstract

Objectives: The study aimed to prepare carbamazepine in solid lipid nanoparticle form (CBZ-SLN) in order to enhance its anticonvulsant effect. Method: Eight formulations of CBZ-SLNs were prepared by homogenization and ultra-sonication techniques. Results: The prepared CBZ-SLN showed a high entrapment efficiency% (39.66 ± [...] Read more.

Objectives: The study aimed to prepare carbamazepine in solid lipid nanoparticle form (CBZ-SLN) in order to enhance its anticonvulsant effect. Method: Eight formulations of CBZ-SLNs were prepared by homogenization and ultra-sonication techniques. Results: The prepared CBZ-SLN showed a high entrapment efficiency% (39.66 ± 2.42%–71.91 ± 1.21%), a small particle size (45.11 ± 6.72–760.7 ± 5.25 nm), and a negative zeta potential (from −21.5 ± 1.02 to −38.4 ± 1.32 mv). The in vitro release study showed the slow release of CBZ from SLNs compared to CBZ aqueous dispersion (p < 0.05). The infrared spectroscopy and the thermal analysis revealed the compatibility of the drug with other ingredients and the presence of drug in the more soluble amorphous estate, respectively. The in vivo study on mice revealed that the CBZ-SLN had a higher anticonvulsant efficacy than CBZ aqueous dispersion after a lethal and chronic dose of pentylenetetrazole (PTZ) (p < 0.05). The histopathological examination of the hippocampus revealed a decrease in the percentage of degeneration in mice treated with the CBZ-SLN compared to the PTZ and CBZ groups. Conclusion: CBZ can be formulated as SLN with higher anticonvulsant activity than free CBZ aqueous dispersion. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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11 pages, 1198 KiB

Open AccessArticle

Praziquantel-Solid Lipid Nanoparticles Produced by Supercritical Carbon Dioxide Extraction: Physicochemical Characterization, Release Profile, and Cytotoxicity

by Luciana N. Andrade, Daniele M.L. Oliveira, Marco V. Chaud, Thais F.R. Alves, Marcelo Nery, Classius F. da Silva, Joyce K.C. Gonsalves, Rogéria S. Nunes, Cristiane B. Corrêa, Ricardo G. Amaral, Elena Sanchez-Lopez, Eliana B. Souto and Patrícia Severino

Molecules 2019, 24(21), 3881; https://doi.org/10.3390/molecules24213881 - 28 Oct 2019

Cited by 39 | Viewed by 3418

Abstract

Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work [...] Read more.

Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~−28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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15 pages, 2686 KiB

Open AccessArticle

Clotrimazole Loaded Ufosomes for Topical Delivery: Formulation Development and In-Vitro Studies

by Pradeep Kumar Bolla, Carlos A. Meraz, Victor A. Rodriguez, Isaac Deaguero, Mahima Singh, Venkata Kashyap Yellepeddi and Jwala Renukuntla

Molecules 2019, 24(17), 3139; https://doi.org/10.3390/molecules24173139 - 29 Aug 2019

Cited by 51 | Viewed by 6990

Abstract

Global incidence of superficial fungal infections caused by dermatophytes is high and affects around 40 million people. It is the fourth most common cause of infection. Clotrimazole, a broad spectrum imidazole antifungal agent is widely used to treat fungal infections. Conventional topical formulations [...] Read more.

Global incidence of superficial fungal infections caused by dermatophytes is high and affects around 40 million people. It is the fourth most common cause of infection. Clotrimazole, a broad spectrum imidazole antifungal agent is widely used to treat fungal infections. Conventional topical formulations of clotrimazole are intended to treat infections by effective penetration of drugs into the stratum corneum. However, drawbacks such as poor dermal bioavailability, poor penetration, and variable drug levels limit the efficiency. The present study aims to load clotrimazole into ufosomes and evaluate its topical bioavailability. Clotrimazole loaded ufosomes were prepared using cholesterol and sodium oleate by thin film hydration technique and evaluated for size, polydispersity index, and entrapment efficiency to obtain optimized formulation. Optimized formulation was characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Skin diffusion studies and tape-stripping were performed using human skin to determine the amount of clotrimazole accumulated in different layers of the skin. Results showed that the optimized formulation had vesicle size <250 nm with ~84% entrapment efficiency. XRD and DSC confirmed the entrapment of clotrimazole into ufosomes. No permeation was observed through the skin up to 24 h following the permeation studies. Tape-stripping revealed that ufosomes led to accumulation of more clotrimazole in the skin compared to marketed formulation (Perrigo). Overall, results revealed the capability of ufosomes in improving the skin bioavailability of clotrimazole. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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17 pages, 4602 KiB

Open AccessArticle

Development and Optimization of Alpha-Pinene-Loaded Solid Lipid Nanoparticles (SLN) Using Experimental Factorial Design and Dispersion Analysis

by Aleksandra Zielińska, Nuno R. Ferreira, Alessandra Durazzo, Massimo Lucarini, Nicola Cicero, Soukaina El Mamouni, Amélia M. Silva, Izabela Nowak, Antonello Santini and Eliana B. Souto

Molecules 2019, 24(15), 2683; https://doi.org/10.3390/molecules24152683 - 24 Jul 2019

Cited by 55 | Viewed by 4998

Abstract

The encapsulation of bicyclic monoterpene α-pinene into solid lipid nanoparticles (SLN) is reported using experimental factorial design, followed by high-end dispersion analyzer LUMiSizer^®. This equipment allows the characterization of the α-pinene-loaded SLN instability phenomena (e.g., sedimentation, flotation or coagulation), as well [...] Read more.

The encapsulation of bicyclic monoterpene α-pinene into solid lipid nanoparticles (SLN) is reported using experimental factorial design, followed by high-end dispersion analyzer LUMiSizer^®. This equipment allows the characterization of the α-pinene-loaded SLN instability phenomena (e.g., sedimentation, flotation or coagulation), as well as the determination of the velocity distribution in the centrifugal field and the particle size distribution. In this work, SLN were produced by hot high-pressure homogenization technique. The influence of the independent variables, surfactant and lipid ratio on the physicochemical properties of SLN, such as mean particle size (Z-Ave), polydispersity index (PDI) and zeta potential (ZP), was estimated using a 2²-factorial design. The Z-Ave and PDI were analyzed by dynamic light scattering, while ZP measurements were recorded by electrophoretic light scattering. Based on the obtained results, the optimal SLN dispersion was composed of 1 wt.% of α-pinene, 4 wt.% of solid lipid (Imwitor^® 900 K) and 2.5 wt.% of surfactant (Poloxamer 188), depicting 136.7 nm of Z-Ave, 0.170 of PDI and 0 mV of ZP. Furthermore, LUMISizer^® has been successfully used in the stability analysis of α-pinene-loaded SLN. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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Review

Jump to: Research

36 pages, 1292 KiB

Open AccessReview

Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery and the Effects of Preparation Parameters of Solvent Injection Method

by Van-An Duong, Thi-Thao-Linh Nguyen and Han-Joo Maeng

Molecules 2020, 25(20), 4781; https://doi.org/10.3390/molecules25204781 - 18 Oct 2020

Cited by 123 | Viewed by 10695

Abstract

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have emerged as potential drug delivery systems for various applications that are produced from physiological, biodegradable, and biocompatible lipids. The methods used to produce SLNs and NLCs have been well investigated and reviewed, but [...] Read more.

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have emerged as potential drug delivery systems for various applications that are produced from physiological, biodegradable, and biocompatible lipids. The methods used to produce SLNs and NLCs have been well investigated and reviewed, but solvent injection method provides an alternative means of preparing these drug carriers. The advantages of solvent injection method include a fast production process, easiness of handling, and applicability in many laboratories without requirement of complicated instruments. The effects of formulations and process parameters of this method on the characteristics of the produced SLNs and NLCs have been investigated in several studies. This review describes the methods currently used to prepare SLNs and NLCs with focus on solvent injection method. We summarize recent development in SLNs and NLCs production using this technique. In addition, the effects of solvent injection process parameters on SLNs and NLCs characteristics are discussed. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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36 pages, 9107 KiB

Open AccessReview

Utilization of Polymer-Lipid Hybrid Nanoparticles for Targeted Anti-Cancer Therapy

by Ayeskanta Mohanty, Saji Uthaman and In-Kyu Park

Molecules 2020, 25(19), 4377; https://doi.org/10.3390/molecules25194377 - 23 Sep 2020

Cited by 72 | Viewed by 8004

Abstract

Cancer represents one of the most dangerous diseases, with 1.8 million deaths worldwide. Despite remarkable advances in conventional therapies, these treatments are not effective to completely eradicate cancer. Nanotechnology offers potential cancer treatment based on formulations of several nanoparticles (NPs). Liposomes and polymeric [...] Read more.

Cancer represents one of the most dangerous diseases, with 1.8 million deaths worldwide. Despite remarkable advances in conventional therapies, these treatments are not effective to completely eradicate cancer. Nanotechnology offers potential cancer treatment based on formulations of several nanoparticles (NPs). Liposomes and polymeric nanoparticle are the most investigated and effective drug delivery systems (DDS) for cancer treatment. Liposomes represent potential DDS due to their distinct properties, including high-drug entrapment efficacy, biocompatibility, low cost, and scalability. However, their use is restricted by susceptibility to lipid peroxidation, instability, burst release of drugs, and the limited surface modification. Similarly, polymeric nanoparticles show several chemical modifications with polymers, good stability, and controlled release, but their drawbacks for biological applications include limited drug loading, polymer toxicity, and difficulties in scaling up. Therefore, polymeric nanoparticles and liposomes are combined to form polymer-lipid hybrid nanoparticles (PLHNPs), with the positive attributes of both components such as high biocompatibility and stability, improved drug payload, controlled drug release, longer circulation time, and superior in vivo efficacy. In this review, we have focused on the prominent strategies used to develop tumor targeting PLHNPs and discuss their advantages and unique properties contributing to an ideal DDS. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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44 pages, 4315 KiB

Open AccessReview

Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties

by Hiba Natsheh and Elka Touitou

Molecules 2020, 25(13), 2959; https://doi.org/10.3390/molecules25132959 - 27 Jun 2020

Cited by 65 | Viewed by 5306

Abstract

This is a comprehensive review on the use of phospholipid nanovesicles for dermal/transdermal and nasal drug administration. Phospholipid-based vesicular carriers have been widely investigated for enhanced drug delivery via dermal/transdermal routes. Classic phospholipid vesicles, liposomes, do not penetrate the deep layers of the [...] Read more.

This is a comprehensive review on the use of phospholipid nanovesicles for dermal/transdermal and nasal drug administration. Phospholipid-based vesicular carriers have been widely investigated for enhanced drug delivery via dermal/transdermal routes. Classic phospholipid vesicles, liposomes, do not penetrate the deep layers of the skin, but remain confined to the upper stratum corneum. The literature describes several approaches with the aim of altering the properties of these vesicles to improve their penetration properties. Transfersomes and ethosomes are the most investigated penetration-enhancing phospholipid nanovesicles, obtained by the incorporation of surfactant edge activators and high concentrations of ethanol, respectively. These two types of vesicles differ in terms of their structure, characteristics, mechanism of action and mode of application on the skin. Edge activators contribute to the deformability and elasticity of transfersomes, enabling them to penetrate through pores much smaller than their own size. The ethanol high concentration in ethosomes generates a soft vesicle by fluidizing the phospholipid bilayers, allowing the vesicle to penetrate deeper into the skin. Glycerosomes and transethosomes, phospholipid vesicles containing glycerol or a mixture of ethanol and edge activators, respectively, are also covered. This review discusses the effects of edge activators, ethanol and glycerol on the phospholipid vesicle, emphasizing the differences between a soft and an elastic nanovesicle, and presents their different preparation methods. To date, these differences have not been comparatively discussed. The review presents a large number of active molecules incorporated in these carriers and investigated in vitro, in vivo or in clinical human tests. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields)

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