Frontiers in the Application of Nanomaterials in Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (10 June 2023) | Viewed by 13653

Special Issue Editors


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Faculty of Biotechnology, CBQF–Centre of Biotechnology and Fine Chemistry–Associate Laboratory, Catholic University of Portugal, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
Interests: polymers from natural source; synthesis and characterization of hydrogels based on natural polysaccharides; nanostructured materials based on biopolymers; extraction, purification and valorization of polysaccharides and bioactive compounds from residues and byproducts
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Pharmaceutical Nanosystems Laboratory – NANOSFAR, Health Sciences Center, Federal University of Piauí - UFPI, Universitaria Avenue. Ininga, Teresina 64049-550, PI, Brazil
Interests: preparation and characterization of nanostructured carriers of drugs and bioactive compounds from biopolymers and natural gums to obtain nanocarriers for antimicrobial use, cardiovascular diseases, diabetes, neglected diseases, neurodegenerative diseases, skin diseases and others

Special Issue Information

Dear Colleagues,

Nanomaterials can be obtained naturally, synthesized from a variety of processes or produced for a specific purpose using nanotechnology and vary in size, shape, surface and chemical composition. Nanomaterials can compose nanocapsules, nanoespheres, nanotubes, among other nanostructures, are able to move easily throughout tissues and cells due to their small size, and it can be considered as an emerging and promising drug delivery system. Nanomaterials can be designed and tuned to have special physicochemical and biological properties, aiming to interact with specific tissues, pH, temperature, and additionally, providing controlled release of the drug or bioactive compound. Besides, this type of drug delivery system can reduce significantly the toxicity and the side effects of the drug, increasing the interest for innovative nanodrugs. However, despite the great future of nanomaterials in this field, there are many challenges to overcome and opportunities that it is urgent to discuss.  Aiming to provide high quality knowledge on the actual scenario, the perspectives, trends, and legislation of nanomaterials designed for drug delivery, in this Special Issue the editors welcome top researchers to contribute in the form of mini reviews and reviews, short communications, opinion articles and research articles. 

Dr. Alessandra Braga Ribeiro
Prof. Dr. Hercilia Rolim
Guest Editors

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Keywords

  • green nanoparticle
  • nanodrugs
  • nanoparticles
  • nanoestructures
  • drug targeting
  • natural products
  • polymer
  • biopolymer

Published Papers (8 papers)

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Research

Jump to: Review

18 pages, 13665 KiB  
Article
Advances in Antitumor Effects Using Liposomal Citrinin in Induced Breast Cancer Model
by Michely Laiany Vieira Moura, Ag-Anne Pereira Melo de Menezes, José Williams Gomes de Oliveira Filho, Maria Luiza Lima Barreto do Nascimento, Antonielly Campinho dos Reis, Alessandra Braga Ribeiro, Felipe Cavalcanti Carneiro da Silva, Adriana Maria Viana Nunes, Hercília Maria Lins Rolim, Ana Amélia de Carvalho Melo Cavalcante and João Marcelo de Castro e Sousa
Pharmaceutics 2024, 16(2), 174; https://doi.org/10.3390/pharmaceutics16020174 - 26 Jan 2024
Viewed by 873
Abstract
The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); [...] Read more.
The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); (3) citrinin, CIT (2 mg/kg), (4) cyclophosphamide, CPA (25 mg/kg), (5) liposomal citrinin, LP-CIT (2 μg/kg), and (6) LP-CIT (6 µg/kg). Metabolic, behavioral, hematological, biochemical, histopathological, and toxicogenetic tests were performed. DMBA and cyclophosphamide induced behavioral changes, not observed for free and liposomal citrinin. No hematological or biochemical changes were observed for LP-CIT. However, free citrinin reduced monocytes and caused hepatotoxicity. During treatment, significant differences were observed regarding the weight of the right and left breasts treated with DMBA compared to negative controls. Treatment with CPA, CIT, and LP-CIT reduced the weight of both breasts, with better results for liposomal citrinin. Furthermore, CPA, CIT, and LP-CIT presented genotoxic effects for tumor, blood, bone marrow, and liver cells, although less DNA damage was observed for LP-CIT compared to CIT and CPA. Healthy cell damage induced by LP-CIT was repaired during treatment, unlike CPA, which caused clastogenic effects. Thus, LP-CIT showed advantages for its use as a model of nanosystems for antitumor studies. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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21 pages, 6672 KiB  
Article
Development and Characterization of Methyl-Anthranilate-Loaded Silver Nanoparticles: A Phytocosmetic Sunscreen Gel for UV Protection
by Mohammed Ghazwani, Umme Hani, Mohammed H. Alqarni and Aftab Alam
Pharmaceutics 2023, 15(5), 1434; https://doi.org/10.3390/pharmaceutics15051434 - 08 May 2023
Cited by 1 | Viewed by 1731
Abstract
Methyl anthranilate (MA) is a naturally derived compound commonly used in cosmetic products, such as skin care products, fine perfumes, etc. The goal of this research was to develop a UV-protective sunscreen gel using methyl-anthranilate-loaded silver nanoparticles (MA-AgNPs). The microwave approach was used [...] Read more.
Methyl anthranilate (MA) is a naturally derived compound commonly used in cosmetic products, such as skin care products, fine perfumes, etc. The goal of this research was to develop a UV-protective sunscreen gel using methyl-anthranilate-loaded silver nanoparticles (MA-AgNPs). The microwave approach was used to develop the MA-AgNPs, which were then optimized using Box–Behnken Design (BBD). Particle size (Y1) and absorbance (Y2) were chosen as the response variables, while AgNO3 (X1), methyl anthranilate concentration (X2), and microwave power (X3) were chosen as the independent variables. Additionally, the prepared AgNPs were approximated for investigations on in vitro active ingredient release, dermatokinetics, and confocal laser scanning microscopy (CLSM). The study’s findings showed that the optimal MA-loaded AgNPs formulation had a particle size, polydispersity index, zeta potential, and percentage entrapment efficiency (EE) of 200 nm, 0.296 mV, −25.34 mV, and 87.88%, respectively. The image from transmission electron microscopy (TEM) demonstrated the spherical shape of the nanoparticles. According to an in vitro investigation on active ingredient release, MA-AgNPs and MA suspension released the active ingredient at rates of 81.83% and 41.62%, respectively. The developed MA-AgNPs formulation was converted into a gel by using Carbopol 934 as a gelling agent. The spreadability and extrudability of MA-AgNPs gel were found to be 16.20 and 15.190, respectively, demonstrating that the gel may spread very easily across the skin’s surface. The MA-AgNPs formulation demonstrated improved antioxidant activity in comparison to pure MA. The MA-AgNPs sunscreen gel formulation displayed non-Newtonian pseudoplastic behaviour, which is typical of skin-care products, and was found to be stable during the stability studies. The sun protection factor (SPF) value of MA-AgNPG was found to be 35.75. In contrast to the hydroalcoholic Rhodamine B solution (5.0 µm), the CLSM of rat skin treated with the Rhodamine B-loaded AgNPs formulation showed a deeper penetration of 35.0 µm, indicating the AgNPs formulation was able to pass the barrier and reach the skin’s deeper layers for more efficient delivery of the active ingredient. This can help with skin conditions where deeper penetration is necessary for efficacy. Overall, the results indicated that the BBD-optimized MA-AgNPs provided some of the most important benefits over conventional MA formulations for the topical delivery of methyl anthranilate. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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17 pages, 2196 KiB  
Article
Comparison of Compartmental and Non-Compartmental Analysis to Detect Biopharmaceutical Similarity of Intravenous Nanomaterial-Based Rifabutin Formulations
by Nadezhda Osipova, Andrey Budko, Olga Maksimenko, Elena Shipulo, Ludmila Vanchugova, Wenqian Chen, Svetlana Gelperina and Matthias G. Wacker
Pharmaceutics 2023, 15(4), 1258; https://doi.org/10.3390/pharmaceutics15041258 - 17 Apr 2023
Cited by 7 | Viewed by 1630
Abstract
Pharmacometric analysis is often used to quantify the differences and similarities between formulation prototypes. In the regulatory framework, it plays a significant role in the evaluation of bioequivalence. While non-compartmental analysis provides an unbiased data evaluation, mechanistic compartmental models such as the physiologically-based [...] Read more.
Pharmacometric analysis is often used to quantify the differences and similarities between formulation prototypes. In the regulatory framework, it plays a significant role in the evaluation of bioequivalence. While non-compartmental analysis provides an unbiased data evaluation, mechanistic compartmental models such as the physiologically-based nanocarrier biopharmaceutics model promise improved sensitivity and resolution for the underlying causes of inequivalence. In the present investigation, both techniques were applied to two nanomaterial-based formulations for intravenous injection, namely, albumin-stabilized rifabutin nanoparticles and rifabutin-loaded PLGA nanoparticles. The antibiotic rifabutin holds great potential for the treatment of severe and acute infections of patients co-infected with human immunodeficiency virus and tuberculosis. The formulations differ significantly in their formulation and material attributes, resulting in an altered biodistribution pattern as confirmed in a biodistribution study in rats. The albumin-stabilized delivery system further undergoes a dose-dependent change in particle size which leads to a small yet significant change in the in vivo performance. A second analysis was conducted comparing the dose fraction-scaled pharmacokinetic profiles of three dose levels of albumin-stabilized rifabutin nanoparticles. The dose strength affects both the nanomaterial-related absorption and biodistribution of the carrier as well as the drug-related distribution and elimination parameters, increasing the background noise and difficulty of detecting inequivalence. Depending on the pharmacokinetic parameter (e.g., AUC, Cmax, Clobs), the relative (percentage) difference from the average observed using non-compartmental modeling ranged from 85% to 5.2%. A change in the formulation type (PLGA nanoparticles vs. albumin-stabilized rifabutin nanoparticles) resulted in a similar level of inequivalence as compared to a change in the dose strength. A mechanistic compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model led to an average difference of 152.46% between the two formulation prototypes. Albumin-stabilized rifabutin nanoparticles tested at different dose levels led to a 128.30% difference, potentially due to changes in particle size. A comparison of different dose strengths of PLGA nanoparticles, on average, led to a 3.87% difference. This study impressively illustrates the superior sensitivity of mechanistic compartmental analysis when dealing with nanomedicines. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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19 pages, 5266 KiB  
Article
Design of Innovative Biocompatible Cellulose Nanostructures for the Delivery and Sustained Release of Curcumin
by Francisca Casanova, Carla F. Pereira, Alessandra B. Ribeiro, Eduardo M. Costa, Ricardo Freixo, Pedro M. Castro, João C. Fernandes, Manuela Pintado and Óscar L. Ramos
Pharmaceutics 2023, 15(3), 981; https://doi.org/10.3390/pharmaceutics15030981 - 18 Mar 2023
Cited by 4 | Viewed by 1746
Abstract
Poor aqueous solubility, stability and bioavailability of interesting bioactive compounds is a challenge in the development of bioactive formulations. Cellulose nanostructures are promising and sustainable carriers with unique features that may be used in enabling delivery strategies. In this work, cellulose nanocrystals (CNC) [...] Read more.
Poor aqueous solubility, stability and bioavailability of interesting bioactive compounds is a challenge in the development of bioactive formulations. Cellulose nanostructures are promising and sustainable carriers with unique features that may be used in enabling delivery strategies. In this work, cellulose nanocrystals (CNC) and cellulose nanofibers were investigated as carriers for the delivery of curcumin, a model liposoluble compound. Nanocellulose modification with the surfactant cetyltrimethylammonium bromide (CTAB), tannic acid and decylamine (TADA), and by TEMPO-mediated oxidation were also tested and compared. The carrier materials were characterized in terms of structural properties and surface charge, while the delivery systems were evaluated for their encapsulation and release properties. The release profile was assessed in conditions that mimic the gastric and intestinal fluids, and cytotoxicity studies were performed in intestinal cells to confirm safe application. Modification with CTAB and TADA resulted in high curcumin encapsulation efficiencies of 90 and 99%, respectively. While no curcumin was released from TADA-modified nanocellulose in simulated gastrointestinal conditions, CNC-CTAB allowed for a curcumin-sustained release of ca. 50% over 8 h. Furthermore, the CNC-CTAB delivery system showed no cytotoxic effects on Caco-2 intestinal cells up to 0.125 g/L, meaning that up to this concentration the system is safe to use. Overall, the use of the delivery systems allowed for the reduction in the cytotoxicity associated with higher curcumin concentrations, highlighting the potential of nanocellulose encapsulation systems. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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19 pages, 2791 KiB  
Article
Synthesis and Characterization of Hierarchical Zeolites Modified with Polysaccharides and Its Potential Role as a Platform for Drug Delivery
by Agata Wawrzyńczak, Izabela Nowak, Natalia Woźniak, Jagoda Chudzińska and Agnieszka Feliczak-Guzik
Pharmaceutics 2023, 15(2), 535; https://doi.org/10.3390/pharmaceutics15020535 - 05 Feb 2023
Cited by 2 | Viewed by 1666
Abstract
Hierarchical zeolites are aluminosilicates with a crystal structure, which next to the micropores possess secondary porosity in the range of mesopores and/or small macropores. Due to their ordered structure and additional secondary porosity, they have aroused great interest among scientists in recent years. [...] Read more.
Hierarchical zeolites are aluminosilicates with a crystal structure, which next to the micropores possess secondary porosity in the range of mesopores and/or small macropores. Due to their ordered structure and additional secondary porosity, they have aroused great interest among scientists in recent years. Therefore, the present work concerns the synthesis and characterization of hierarchical zeolites with secondary mesoporosity, based on commercial zeolites such as MFI (ZSM-5), BEA (β) and FAU (Y), and modified with polysaccharides such as inulin, hyaluronic acid, and heparin. All materials were characterized by various analytical techniques and applied as a platform for delivery of selected drug molecules. On the basis of X-ray diffraction (presence of reflections in the 2θ angle range of 1.5–2.5°) and low-temperature nitrogen sorption isotherms (mixture of isotherms of I and IV type) additional secondary porosity was found in the mesopore range. Additional tests were also conducted to determine the possibility of loading selected molecules with biological activity into the aforementioned materials and then releasing them in the therapeutic process. Molecules with different therapeutic options were selected for testing, namely ibuprofen, curcumin, and ferulic acid with anti-inflammatory, potentially anticancer, antioxidant, and skin discoloration activities, respectively. Preliminary studies have confirmed the possibility of using hierarchical zeolites as potential carriers for bioactive molecules, as the loading percentage of active substances ranged from 39–79% and cumulative release for ibuprofen reached almost 100% after 8 h of testing. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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10 pages, 2783 KiB  
Article
Direct Cytosolic Delivery of Citraconylated Proteins
by Ritabrita Goswami, Victor Lehot, Yağız Anıl Çiçek, Harini Nagaraj, Taewon Jeon, Terry Nguyen, Stefano Fedeli and Vincent M. Rotello
Pharmaceutics 2023, 15(1), 218; https://doi.org/10.3390/pharmaceutics15010218 - 08 Jan 2023
Cited by 5 | Viewed by 2018
Abstract
Current intracellular protein delivery strategies face the challenge of endosomal entrapment and consequent degradation of protein cargo. Methods to efficiently deliver proteins directly to the cytosol have the potential to overcome this hurdle. Here, we report the use of a straightforward approach of [...] Read more.
Current intracellular protein delivery strategies face the challenge of endosomal entrapment and consequent degradation of protein cargo. Methods to efficiently deliver proteins directly to the cytosol have the potential to overcome this hurdle. Here, we report the use of a straightforward approach of protein modification using citraconic anhydride to impart an overall negative charge on the proteins, enabling them to assemble with positively charged nano vectors. This strategy uses anhydride-modified proteins to electrostatically form polymer–protein nanocomposites with a cationic guanidinium-functionalized polymer. These supramolecular self-assemblies demonstrated the efficient cytosolic delivery of modified proteins through a membrane fusion-like mechanism. This approach was validated on five cell lines and seven proteins as cargo. Retention of protein function was confirmed through efficient cell killing via the intracellular enzymatic activity of RNase A. This platform provides a versatile, straightforward, and single-step method of protein modification and efficient direct cytosolic protein delivery. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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14 pages, 3495 KiB  
Article
Nanoparticles Obtained from Zein for Encapsulation of Mesalazine
by Izabela Borges C. Lima, Lina Clara G. A. I. Moreno, Ana Victória Peres, Ana Cristina Gramoza Santana, Adonias Carvalho, Mariana H. Chaves, Lorena Lima, Rayran Walter Sousa, Dalton Dittz, Hercília M. L. Rolim and Lívio César Cunha Nunes
Pharmaceutics 2022, 14(12), 2830; https://doi.org/10.3390/pharmaceutics14122830 - 16 Dec 2022
Cited by 2 | Viewed by 1538
Abstract
We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of −36.4 ± 1.5 mV, suggesting [...] Read more.
We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of −36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas–Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer–Peppas model with the Fickian release mechanism, or “Case I”. An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 μg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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Review

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18 pages, 1282 KiB  
Review
Elucidating Berberine’s Therapeutic and Photosensitizer Potential through Nanomedicine Tools
by Célia Marques, Maria Helena Fernandes and Sofia A. Costa Lima
Pharmaceutics 2023, 15(9), 2282; https://doi.org/10.3390/pharmaceutics15092282 - 05 Sep 2023
Viewed by 1886
Abstract
Berberine, an isoquinoline alkaloid extracted from plants of the Berberidaceae family, has been gaining interest due to anti-inflammatory and antioxidant activities, as well as neuro and cardiovascular protective effects in animal models. Recently, photodynamic therapy demonstrated successful application in many fields of medicine. [...] Read more.
Berberine, an isoquinoline alkaloid extracted from plants of the Berberidaceae family, has been gaining interest due to anti-inflammatory and antioxidant activities, as well as neuro and cardiovascular protective effects in animal models. Recently, photodynamic therapy demonstrated successful application in many fields of medicine. This innovative, non-invasive treatment modality requires a photosensitizer, light, and oxygen. In particular, the photosensitizer can selectively accumulate in diseased tissues without damaging healthy cells. Berberine’s physicochemical properties allow its use as a photosensitising agent for photodynamic therapy, enabling reactive oxygen species production and thus potentiating treatment efficacy. However, berberine exhibits poor aqueous solubility, low oral bioavailability, poor cellular permeability, and poor gastrointestinal absorption that hamper its therapeutic and photodynamic efficacy. Nanotechnology has been used to minimize berberine’s limitations with the design of drug delivery systems. Different nanoparticulate delivery systems for berberine have been used, as lipid-, inorganic- and polymeric-based nanoparticles. These berberine nanocarriers improve its therapeutic properties and photodynamic potential. More specifically, they extend its half-life, increase solubility, and allow a high permeation and targeted delivery. This review describes different nano strategies designed for berberine delivery as well as berberine’s potential as a photosensitizer for photodynamic therapy. To benefit from berberine’s overall potential, nanotechnology has been applied for berberine-mediated photodynamic therapy. Full article
(This article belongs to the Special Issue Frontiers in the Application of Nanomaterials in Drug Delivery)
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