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Pharmaceutics
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Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug...
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Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa

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 (15 November 2022) | Viewed by 26047

Special Issue Editors

Dr. Fiorenza Rancan

E-Mail Website
Guest Editor
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Interests: dermal drug delivery; inflammatory skin diseases; wound infections
Dr. Marco Contardi

E-Mail Website
Co-Guest Editor
Smart Materials, Istituto Italiano di Tecnologia, 16163 Genova, Italy
Interests: wound dressing; wound healing; biomaterials; antioxidants

Special Issue Information

Dear Colleagues,

More efficient topical administration of drugs would improve the specificity and safety of many dermatological conditions. However, low penetration, low stability, rapid clearance, or low specificity still hamper the development of efficient topical treatments. In this regard, nanotechnology-based delivery systems have been shown to improve drug bioavailability and even enable spatiotemporal control of drug release. Nanoparticles, gels, foils, or membranes based on lipids, polysaccharides, proteins, dendrimers, or polymers are promising approaches for topical drug delivery. They can improve skin permeability, dissolve in a controlled manner and possess environmental sensitivity and specific targeting properties. Several synthetic methods have been employed to develop new materials at the nanoscale level. On the other hand, adequate high-resolution spectro-microscopy methods as well as ex vivo or in vivo models have been developed to test the delivery capacity and the efficacy of these new materials.

This Special Issue welcomes articles dealing with drug delivery to wounds, skin, or mucosa with special attention paid to the following topics:

  1. Novel synthesis of delivery systems, drug formulations, or loading techniques;
  2. Drug release, delivery studies;
  3. Studies on the mechanism of drug action or transport across skin barrier;
  4. In vitro, ex vivo, or in vivo tests of efficacy;
  5. Targeting of specific cell populations or intracellular targeting.

Dr. Fiorenza Rancan
Dr. Marco Contardi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • topical drug delivery
  • anti-oxidants
  • skin inflammatory diseases
  • skin and wound infections
  • wound healing
  • dermatomycosis
  • skin cancer

Published Papers (7 papers)

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Research

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25 pages, 3308 KiB  
Article
Transethosomal Gel for the Topical Delivery of Celecoxib: Formulation and Estimation of Skin Cancer Progression
by Ahmed A. H. Abdellatif, Basmah Nasser Aldosari, Amal Al-Subaiyel, Aisha Alhaddad, Waad A. Samman, Nermin E. Eleraky, Marwa G. Elnaggar, Hassan Barakat and Hesham M. Tawfeek
Pharmaceutics 2023, 15(1), 22; https://doi.org/10.3390/pharmaceutics15010022 - 21 Dec 2022
Cited by 6 | Viewed by 2735
Abstract
The topical delivery of therapeutics is a promising strategy for managing skin conditions. Cyclooxygenase-2 (COX-2) inhibitors showed a possible target for chemoprevention and cancer management. Celecoxib (CXB) is a selective COX-2 inhibitor that impedes cell growth and generates apoptosis in different cell tumors. [...] Read more.
The topical delivery of therapeutics is a promising strategy for managing skin conditions. Cyclooxygenase-2 (COX-2) inhibitors showed a possible target for chemoprevention and cancer management. Celecoxib (CXB) is a selective COX-2 inhibitor that impedes cell growth and generates apoptosis in different cell tumors. Herein, an investigation proceeded to explore the usefulness of nano lipid vesicles (transethosomes) (TES) of CXB to permit penetration of considerable quantities of the drug for curing skin cancer. The prepared nanovesicles were distinguished for drug encapsulation efficiency, vesicle size, PDI, surface charge, and morphology. In addition, FT-IR and DSC analyses were also conducted to examine the influence of vesicle components. The optimized formulation was dispersed in various hydrogel bases. Furthermore, in vitro CXB release and ex vivo permeability studies were evaluated. A cytotoxicity study proceeded using A431 and BJ1 cell lines. The expression alteration of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and DNA damage and fragmentation using qRT-PCR and comet assays were also investigated. Optimized CXB-TES formulation was spherically shaped and displayed a vesicle size of 75.9 ± 11.4 nm, a surface charge of −44.7 ± 1.52 mV, and an entrapment efficiency of 88.8 ± 7.2%. The formulated TES-based hydrogel displayed a sustained in vitro CXB release pattern for 24 h with an enhanced flux and permeation across rat skin compared with the control (free drug-loaded hydrogel). Interestingly, CXB-TES hydrogel has a lower cytotoxic effect on normal skin cells compared with TES suspension and CXB powder. Moreover, the level of expression of the CDKN2A gene was significantly (p ≤ 0.01, ANOVA/Tukey) decreased in skin tumor cell lines compared with normal skin cell lines, indicating that TES are the suitable carrier for topical delivery of CXB to the cancer cells suppressing their progression. In addition, apoptosis demonstrated by comet and DNA fragmentation assays was evident in skin cancer cells exposed to CXB-loaded TES hydrogel formulation. In conclusion, our results illustrate that CXB-TES-loaded hydrogel could be considered a promising carrier and effective chemotherapeutic agent for the management of skin carcinoma. Full article
(This article belongs to the Special Issue Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa)
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18 pages, 29243 KiB  
Article
Resina Draconis Particles Encapsulated in a Hyaluronic-Acid-Based Hydrogel to Treat Complex Burn Wounds
by Lijun Xu, Ziqiang Zhou, Yuying Chen, Huangjie Lu and Ping Hu
Pharmaceutics 2022, 14(10), 2087; https://doi.org/10.3390/pharmaceutics14102087 - 29 Sep 2022
Cited by 2 | Viewed by 2043
Abstract
Severe burns require urgent new dressing treatments due to their irregular wounds and secondary injuries associated with dressing changes. In this study, a hyaluronic-acid-based hydrogel was developed to treat complex burn wounds. This hydrogel was prepared by mixing and cross-linking oxidized hyaluronic acid [...] Read more.
Severe burns require urgent new dressing treatments due to their irregular wounds and secondary injuries associated with dressing changes. In this study, a hyaluronic-acid-based hydrogel was developed to treat complex burn wounds. This hydrogel was prepared by mixing and cross-linking oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS) through Schiff base reactions. Micronized Resina Draconis particles were encapsulated in this hydrogel to achieve sustained release of the active components when applied on wounds. The Resina-Draconis-loaded hydrogel (RD-Gel) demonstrated good mechanical properties and excellent self-healing. The results of in vitro experiments confirmed that RD-Gel had good biocompatibility, and was able to enhance cell migration and inhibit the production of inflammatory cytokines. It also induced rapid hemostasis in rats, downregulated the levels of inflammatory cytokines, and promoted collagen regeneration on model animals, eventually accelerating the rebuilding of skin structures and wound recovery. Full article
(This article belongs to the Special Issue Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa)
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15 pages, 4886 KiB  
Article
Screening of Surfactants for Improved Delivery of Antimicrobials and Poly-Lactic-co-Glycolic Acid Particles in Wound Tissue
by Fiorenza Rancan, Jana Jurisch, Cemre Günday, Emre Türeli, Ulrike Blume-Peytavi, Annika Vogt, Christoph Schaudinn and Nazende Günday-Türeli
Pharmaceutics 2021, 13(7), 1093; https://doi.org/10.3390/pharmaceutics13071093 - 17 Jul 2021
Cited by 5 | Viewed by 3206
Abstract
Topical wound management is often a challenge due to the poor penetration of antimicrobials in wound tissue and across the biofilm matrix where bacteria are embedded. Surfactants have been used for decades to improve the stability of formulations, increase drug solubility, and enhance [...] Read more.
Topical wound management is often a challenge due to the poor penetration of antimicrobials in wound tissue and across the biofilm matrix where bacteria are embedded. Surfactants have been used for decades to improve the stability of formulations, increase drug solubility, and enhance penetration. In this study, we screened different detergents with respect to their cytotoxicity and their ability to improve the penetration of poly-lactic-co-glycolic acid (PLGA) particles in wound tissue. Among the tested surfactants, Kolliphor SLS and Tween 80 increased the penetration of PLGA particles and had a limited cytotoxicity. Then, these surfactants were used to formulate PLGA particles loaded with the poorly water-soluble antibiotic ciprofloxacin. The antimicrobial efficacy of the formulations was tested in a wound infection model based on human ex vivo skin. We found that even though PLGA particles had the same antimicrobial efficiency than the particle-free drug formulation, thanks to their solubilizing and anti-biofilm properties, the surfactants remarkably improved the antimicrobial activity of ciprofloxacin with respect to the drug formulation in water. We conclude that the use of Tween 80 in antimicrobial formulations might be a safe and efficient option to improve the topical antimicrobial management of chronic wound infections. Full article
(This article belongs to the Special Issue Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa)
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22 pages, 7170 KiB  
Article
The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo
by Maria Natalia Calienni, Daniela Maza Vega, C. Facundo Temprana, María Cecilia Izquierdo, David E. Ybarra, Ezequiel Bernabeu, Marcela Moretton, Fernando C. Alvira, Diego Chiappetta, Silvia del Valle Alonso, María Jimena Prieto and Jorge Montanari
Pharmaceutics 2021, 13(2), 186; https://doi.org/10.3390/pharmaceutics13020186 - 01 Feb 2021
Cited by 9 | Viewed by 3169
Abstract
Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. [...] Read more.
Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility. Full article
(This article belongs to the Special Issue Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa)
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22 pages, 6071 KiB  
Article
Chitosan Film Containing Mansoa hirsuta Fraction for Wound Healing
by Joquebede Rodrigues Pereira, Gabriela Suassuna Bezerra, Allanny Alves Furtado, Thaís Gomes de Carvalho, Valéria Costa da Silva, Amanda Lins Bispo Monteiro, Gerlane Coelho Bernardo Guerra, Raimundo Fernandes de Araújo Júnior, Antônio Euzébio Goulart Sant’Ana, Matheus de Freitas Fernandes-Pedrosa, Daniel de Melo Silva, Eduardo Pereira de Azevedo, Tania Maria Sarmento Silva, Telma Maria Araújo Moura Lemos and Ádley Antonini Neves de Lima
Pharmaceutics 2020, 12(6), 484; https://doi.org/10.3390/pharmaceutics12060484 - 27 May 2020
Cited by 13 | Viewed by 4177
Abstract
Chitosan films entrapped with the Mansoa hirsuta fraction (CMHF) was developed as a new dressing for wound care. The chromatographic profile of the M. hirsuta fraction (MHF) was evaluated by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and the results showed that MHF is [...] Read more.
Chitosan films entrapped with the Mansoa hirsuta fraction (CMHF) was developed as a new dressing for wound care. The chromatographic profile of the M. hirsuta fraction (MHF) was evaluated by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and the results showed that MHF is rich in acid triterpenes. Physicochemical characterization of the films prepared using the solvent casting method was performed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetry (TGA), differential scanning calorimetry (DCS), scanning electron microscopy (SEM), atomic force microscopy (AFM), and mechanical properties. CMHF exhibited characteristic bands of both chitosan and MHF, revealing a physical mixture of both. CMHF presented an amorphous nature, thermostability, and dispersion of MHF in the chitosan matrix, resulting in a rough structure. Incorporation of M. hirsuta fraction into chitosan matrix favorably enhanced the mechanical performance and films thickness. The in vivo wound treatment with CMHF for seven days showed a characteristic area of advanced healing, re-epithelization, cell proliferation, and collagen formation. Furthermore, wound closure reached 100% contraction after 10 days of treatment with modulation of interleukins. The incorporation of M. hirsuta fraction into chitosan films was advantageous and showed great potential for stimulating wound repair and regeneration. Full article
(This article belongs to the Special Issue Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa)
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Review

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33 pages, 1662 KiB  
Review
Hydroxycinnamic Acids and Derivatives Formulations for Skin Damages and Disorders: A Review
by Marco Contardi, Martina Lenzuni, Fabrizio Fiorentini, Maria Summa, Rosalia Bertorelli, Giulia Suarato and Athanassia Athanassiou
Pharmaceutics 2021, 13(7), 999; https://doi.org/10.3390/pharmaceutics13070999 - 01 Jul 2021
Cited by 30 | Viewed by 5987
Abstract
Alterations of skin homeostasis are widely diffused in our everyday life both due to accidental injuries, such as wounds and burns, and physiological conditions, such as late-stage diabetes, dermatitis, or psoriasis. These events are locally characterized by an intense inflammatory response, a high [...] Read more.
Alterations of skin homeostasis are widely diffused in our everyday life both due to accidental injuries, such as wounds and burns, and physiological conditions, such as late-stage diabetes, dermatitis, or psoriasis. These events are locally characterized by an intense inflammatory response, a high generation of harmful free radicals, or an impairment in the immune response regulation, which can profoundly change the skin tissue’ repair process, vulnerability, and functionality. Moreover, diabetes diffusion, antibiotic resistance, and abuse of aggressive soaps and disinfectants following the COVID-19 emergency could be causes for the future spreading of skin disorders. In the last years, hydroxycinnamic acids and derivatives have been investigated and applied in several research fields for their anti-oxidant, anti-inflammatory, and anti-bacterial activities. First, in this study, we give an overview of these natural molecules’ current source and applications. Afterwards, we review their potential role as valid alternatives to the current therapies, supporting the management and rebalancing of skin disorders and diseases at different levels. Also, we will introduce the recent advances in the design of biomaterials loaded with these phenolic compounds, specifically suitable for skin disorders treatments. Lastly, we will suggest future perspectives for introducing hydroxycinnamic acids and derivatives in treating skin disorders. Full article
(This article belongs to the Special Issue Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa)
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18 pages, 1350 KiB  
Review
Extracellular Vesicles as Potential Theranostic Platforms for Skin Diseases and Aging
by Hyosuk Kim, Jong Won Lee, Geonhee Han, Kwangmeyung Kim, Yoosoo Yang and Sun Hwa Kim
Pharmaceutics 2021, 13(5), 760; https://doi.org/10.3390/pharmaceutics13050760 - 20 May 2021
Cited by 10 | Viewed by 3702
Abstract
Extracellular vesicles (EVs), naturally secreted by cells, act as mediators for communication between cells. They are transported to the recipient cells along with cargoes such as nucleic acids, proteins, and lipids that reflect the changes occurring within the parent cells. Thus, EVs have [...] Read more.
Extracellular vesicles (EVs), naturally secreted by cells, act as mediators for communication between cells. They are transported to the recipient cells along with cargoes such as nucleic acids, proteins, and lipids that reflect the changes occurring within the parent cells. Thus, EVs have been recognized as potential theranostic agents for diagnosis, treatment, and prognosis. In particular, the evidence accumulated to date suggests an important role of EVs in the initiation and progression of skin aging and various skin diseases, including psoriasis, systemic lupus erythematosus, vitiligo, and chronic wounds. This review highlights recent research that investigates the role of EVs and their potential as biomarkers and therapeutic agents for skin diseases and aging. Full article
(This article belongs to the Special Issue Development and Testing of Nanotechnology-Based Delivery Systems for Topical Drug Delivery to Wounds, Skin or Mucosa)
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