Recent Advances in Skin Drug Delivery

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 18296

Special Issue Editors


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Guest Editor
Helmholtz Institute for Pharmaceutical Research Saarland, 66123 Saarbrücken, Germany
Interests: transdermal drug delivery; topical application; thermotropic liquid crystals; prodrugs for transdermal delivery

E-Mail Website
Guest Editor
Helmholtz Institute for Pharmaceutical Research Saarland, 66123 Saarbrücken, Germany
Interests: biological barriers; drug delivery systems; nanoparticles; liposomes

E-Mail Website
Guest Editor
Helmholtz Institute for Pharmaceutical Research Saarland, 66123 Saarbrücken, Germany
Interests: thermoresponsive liquid crystals; natural products in drug delivery; topical application; prodrugs

Special Issue Information

Dear Colleagues,

Skin drug delivery is associated with a convenient noninvasive, targeted, and on-demand route of administration for the treatment of various diseases. Although skin constitutes an ideal platform to achieve both local and systemic effects of drug substances, skin drug delivery remains challenging due to the protective properties of the skin barrier, which consequently often limits the penetration and permeation of drug molecules.

A variety of methods have been developed to investigate and eventually improve skin penetration and permeation, including chemical enhancers, novel formulations and physical approaches. Improved penetration-enhancement strategies led to a resurgence of interest in transdermal drug delivery to the systemic circulation. Given that only a small number of transdermal formulations are commercially available, further advancement of skin drug delivery requires the development of novel delivery systems and approaches that are suitable for compounds distinguished by physicochemical properties and molecular sizes.

Undoubtedly, any targeted and active skin drug delivery vision promoting increased drug bioavailability should comprise an encouraging approach for the safe and efficient transfer of therapeutic molecules. On the other hand, no less important is the delivery of topical drugs directly to various skin structures with minimal penetration into the systemic circulation.  

This Special Issue aims to provide readers with the recent advancements in drug delivery across the skin, for both topical and systemic applications. We welcome the submission of original research and review articles focused on the above-described subjects.

Dr. Iryna Kravchenko
Prof. Dr. Claus-Michael Lehr
Dr. Mariia Nesterkina
Guest Editors

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Keywords

  • skin drug delivery
  • permeation and penetration
  • physical and chemical enhancers
  • nanoparticles and nanocarriers
  • 3D printed forms
  • microneedles
  • liquid crystals
  • sustained/controlled release
  • therapy ultrasound
  • liposomes
  • topical application
  • skin segmentation
  • phospholipids

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Published Papers (7 papers)

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Research

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14 pages, 2153 KiB  
Article
Span 60/Cholesterol Niosomal Formulation as a Suitable Vehicle for Gallic Acid Delivery with Potent In Vitro Antibacterial, Antimelanoma, and Anti-Tyrosinase Activity
by Sara Zolghadri, Ali Ghanbari Asad, Fatemeh Farzi, Fatemeh Ghajarzadeh, Zeinab Habibi, Mahdie Rahban, Samaneh Zolghadri and Agata Stanek
Pharmaceuticals 2023, 16(12), 1680; https://doi.org/10.3390/ph16121680 - 2 Dec 2023
Cited by 3 | Viewed by 1739
Abstract
Natural compounds such as gallic acid (GA) have attracted more attention in cosmetic and pharmaceutical skin care products. However, the low solubility and poor stability of GA have limited its application. This study aimed to synthesize and characterize the GA niosomal dispersion (GAN) [...] Read more.
Natural compounds such as gallic acid (GA) have attracted more attention in cosmetic and pharmaceutical skin care products. However, the low solubility and poor stability of GA have limited its application. This study aimed to synthesize and characterize the GA niosomal dispersion (GAN) and investigate the potential of an optimal formulation as a skin drug delivery system for GA. For this purpose, GAN formulations were synthesized using the thin layer evaporation method with different molar ratios of Tween 60/Span 60, along with a constant molar ratio of polyethylene glycol 4000 (PEG-4000) and cholesterol in a methanol and chloroform solvent (1:4 v/v). The physicochemical properties of nanosystems in terms of size, zeta potential, drug entrapment, drug release, morphology, and system–drug interaction were characterized using different methods. In addition, in vitro cytotoxicity, anti-tyrosinase activity, and antibacterial activity were evaluated by MTT assay, the spectrophotometric method, and micro-well dilution assay. All formulations revealed a size of 80–276 nm, polydispersity index (PDI) values below 0.35, and zeta potential values below—9.7 mV. F2 was selected as the optimal formulation due to its smaller size and high stability. The optimal formulation of GAN (F2) was as follows: a 1:1 molar ratio of Span 60 to cholesterol and 1.5 mM GA. The release of the F2 drug showed a biphasic pattern, which was fast in the first 12 h until 58% was released. Our results showed the high antibacterial activity of GAN against Escherichia coli and Pseudomonas aeruginosa. The MTT assay showed that GA encapsulation increased its effect on B6F10 cancer cells. The F2 formulation exhibited potent anti-tyrosinase activity and inhibited melanin synthesis. These findings suggest that it can be used in dermatological skin care products in the cosmetic and pharmaceutical industries due to its significant antibacterial, anti-melanoma, and anti-tyrosinase activity. Full article
(This article belongs to the Special Issue Recent Advances in Skin Drug Delivery)
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21 pages, 15573 KiB  
Article
The Development of Dermal Self-Double-Emulsifying Drug Delivery Systems: Preformulation Studies as the Keys to Success
by Daniélle van Staden, Richard K. Haynes and Joe M. Viljoen
Pharmaceuticals 2023, 16(10), 1348; https://doi.org/10.3390/ph16101348 - 25 Sep 2023
Viewed by 1339
Abstract
Self-emulsifying drug delivery systems (SEDDSs) are lipid-based systems that are superior to other lipid-based oral drug delivery systems in terms of providing drug protection against the gastrointestinal (GI) environment, inhibition of drug efflux as mediated by P-glycoprotein, enhanced lymphatic drug uptake, improved control [...] Read more.
Self-emulsifying drug delivery systems (SEDDSs) are lipid-based systems that are superior to other lipid-based oral drug delivery systems in terms of providing drug protection against the gastrointestinal (GI) environment, inhibition of drug efflux as mediated by P-glycoprotein, enhanced lymphatic drug uptake, improved control over plasma concentration profiles of drugs, enhanced stability, and drug loading efficiency. Interest in dermal spontaneous emulsions has increased, given that systems have been reported to deliver drugs across mucus membranes, as well as the outermost layer of the skin into the underlying layers. The background and development of a double spontaneous emulsion incorporating four anti-tubercular drugs, clofazimine (CFZ), isoniazid (INH), pyrazinamide (PZY), and rifampicin (RIF), are described here. Our methods involved examination of oil miscibility, the construction of pseudoternary phase diagrams, the determination of self-emulsification performance and the emulsion stability index of primary emulsions (PEs), solubility, and isothermal micro calorimetry compatibility and examination of emulsions via microscopy. Overall, the potential of self-double-emulsifying drug delivery systems (SDEDDSs) as a dermal drug delivery vehicle is now demonstrated. The key to success here is the conduct of preformulation studies to enable the development of dermal SDEDDSs. To our knowledge, this work represents the first successful example of the production of SDEDDSs capable of incorporating four individual drugs. Full article
(This article belongs to the Special Issue Recent Advances in Skin Drug Delivery)
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13 pages, 1378 KiB  
Article
Follicle-Targeted Delivery of Betamethasone and Minoxidil Co-Entrapped in Polymeric and Lipid Nanoparticles for Topical Alopecia Areata Treatment
by Breno N. Matos, Ana Luiza Lima, Camila O. Cardoso, Marcilio Cunha-Filho, Tais Gratieri and Guilherme M. Gelfuso
Pharmaceuticals 2023, 16(9), 1322; https://doi.org/10.3390/ph16091322 - 19 Sep 2023
Cited by 1 | Viewed by 2205
Abstract
Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient’s adherence [...] Read more.
Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient’s adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 ± 13.0% minoxidil and 70.2 ± 12.8% betamethasone, while the NLCs entrapped 99.4 ± 0.1 minoxidil and 80.7 ± 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 ± 10 nm to 567 ± 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs. Full article
(This article belongs to the Special Issue Recent Advances in Skin Drug Delivery)
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15 pages, 2141 KiB  
Article
Nanogel Containing Gamma-Oryzanol-Loaded Nanostructured Lipid Carriers and TiO2/MBBT: A Synergistic Nanotechnological Approach of Potent Natural Antioxidants and Nanosized UV Filters for Skin Protection
by Omolbanin Badalkhani, Patrícia C. Pires, Maryam Mohammadi, Soraya Babaie, Ana Cláudia Paiva-Santos and Hamed Hamishehkar
Pharmaceuticals 2023, 16(5), 670; https://doi.org/10.3390/ph16050670 - 28 Apr 2023
Cited by 6 | Viewed by 2057
Abstract
The human skin is a recurring target of external aggressions, such as UV radiation, leading to exacerbation of the aging process and the occurrence of skin diseases, such as cancer. Hence, preventive measures should be taken to protect it against these aggressions, consequently [...] Read more.
The human skin is a recurring target of external aggressions, such as UV radiation, leading to exacerbation of the aging process and the occurrence of skin diseases, such as cancer. Hence, preventive measures should be taken to protect it against these aggressions, consequently decreasing the chance of disease development. In the present study, a topical xanthan gum nanogel containing gamma-oryzanol-loaded nanostructured lipid carriers (NLCs) and nanosized UV filters TiO2 and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) was developed to assess their synergistic potential in having multifunctional skin beneficial properties. The developed NLCs contained the natural-based solid lipids shea butter and beeswax, liquid lipid carrot seed oil, and the potent antioxidant gamma-oryzanol, with an optimum particle size for topical application (<150 nm), good homogeneity (PDI = 0.216), high zeta potential (−34.9 mV), suitable pH value (6), good physical stability, high encapsulation efficiency (90%), and controlled release. The final formulation, a nanogel containing the developed NLCs and the nano UV filters, showed high long-term storage stability and high photoprotection ability (SPF = 34) and resulted in no skin irritation or sensitization (rat model). Hence, the developed formulation showed good skin protection and compatibility, demonstrating promise as a new platform for the future generation of natural-based cosmeceuticals. Full article
(This article belongs to the Special Issue Recent Advances in Skin Drug Delivery)
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18 pages, 3614 KiB  
Article
Enhanced Skin Permeation and Controlled Release of β-Sitosterol Using Cubosomes Encrusted with Dissolving Microneedles for the Management of Alopecia
by Kousalya Prabahar, Ubaidulla Uthumansha, Nehal Elsherbiny and Mona Qushawy
Pharmaceuticals 2023, 16(4), 563; https://doi.org/10.3390/ph16040563 - 8 Apr 2023
Cited by 4 | Viewed by 2342
Abstract
The use of synthetic medication for treating alopecia is restricted because of systemic exposure and related negative effects. Beta-sitosterol (β-ST), a natural chemical, has lately been studied for its potential to promote hair development. The cubosomes with dissolving microneedles (CUBs-MND) created [...] Read more.
The use of synthetic medication for treating alopecia is restricted because of systemic exposure and related negative effects. Beta-sitosterol (β-ST), a natural chemical, has lately been studied for its potential to promote hair development. The cubosomes with dissolving microneedles (CUBs-MND) created in this study may be a useful starting point for the creation of a sophisticated dermal delivery system for β-ST. Cubosomes (CUBs) were prepared by the emulsification method, using glyceryl monooleate (GMO) as a lipid polymer. CUBs were loaded with dissolving microneedles (MND) fabricated with HA and a PVP-K90 matrix. An ex vivo skin permeation study and an in vivo hair growth efficacy test of β-ST were performed with both CUB and CUB-MND. The average particle size of the CUBs was determined to be 173.67 ± 0.52 nm, with a low polydispersity index (0.3) and a high zeta potential value that prevents the aggregate formation of dispersed particles. When compared to CUBs alone, CUBs-MND displayed higher permeating levels of β-ST at all-time points. In the animals from the CUB-MND group, significant hair development was observed. According to the results of the current investigation, CUBs that integrate dissolving microneedles of β-ST are superior in terms of transdermal skin penetration and activity for the treatment of alopecia. Full article
(This article belongs to the Special Issue Recent Advances in Skin Drug Delivery)
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12 pages, 1527 KiB  
Article
Topical Delivery of Cell-Penetrating Peptide-Modified Human Growth Hormone for Enhanced Wound Healing
by Tru Van Nguyen, Kyung-Hwa Lee, Yongzhuo Huang, Meong Cheol Shin, Yoon Shin Park, Hangun Kim and Cheol Moon
Pharmaceuticals 2023, 16(3), 394; https://doi.org/10.3390/ph16030394 - 5 Mar 2023
Cited by 7 | Viewed by 2857
Abstract
Protein drugs have been emerging as a class of promising therapeutics. However, their topical application has been limited by their high molecular weight and poor permeability to the cell membrane. In this study, we aimed to enhance human growth hormone (hGH) permeability for [...] Read more.
Protein drugs have been emerging as a class of promising therapeutics. However, their topical application has been limited by their high molecular weight and poor permeability to the cell membrane. In this study, we aimed to enhance human growth hormone (hGH) permeability for topical application by conjugation of TAT peptide, a cell-penetrating peptide, to hGH via crosslinker. After TAT was conjugated to hGH, TAT-hGH was purified by affinity chromatography. TAT-hGH significantly increased cell proliferation compared with the control. Interestingly, the effect of TAT-hGH was higher than hGH at the same concentration. Furthermore, the conjugation of TAT to hGH enhanced the permeability of TAT-hGH across the cell membrane without affecting its biological activity in vitro. In vivo, the topical application of TAT-hGH into scar tissue markedly accelerated wound healing. Histological results showed that TAT-hGH dramatically promoted the re-epithelialization of wounds in the initial stage. These results demonstrate TAT-hGH as a new therapeutic potential drug for wound healing treatment. This study also provides a new method for topical protein application via enhancement of their permeability. Full article
(This article belongs to the Special Issue Recent Advances in Skin Drug Delivery)
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Review

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19 pages, 4800 KiB  
Review
Topical Microemulsions: Skin Irritation Potential and Anti-Inflammatory Effects of Herbal Substances
by Jiraporn Leanpolchareanchai and Veerawat Teeranachaideekul
Pharmaceuticals 2023, 16(7), 999; https://doi.org/10.3390/ph16070999 - 13 Jul 2023
Cited by 3 | Viewed by 3797
Abstract
Microemulsions (MEs) have gained prominence as effective drug delivery systems owing to their optical transparency, low viscosity, and thermodynamic stability. MEs, when stabilized with surfactants and/or co-surfactants, exhibit enhanced drug solubilization, prolonged shelf life, and simple preparation methods. This review examines the various [...] Read more.
Microemulsions (MEs) have gained prominence as effective drug delivery systems owing to their optical transparency, low viscosity, and thermodynamic stability. MEs, when stabilized with surfactants and/or co-surfactants, exhibit enhanced drug solubilization, prolonged shelf life, and simple preparation methods. This review examines the various types of MEs, explores different preparation techniques, and investigates characterization approaches. Plant extracts and bioactive compounds are well established for their utilization as active ingredients in the pharmaceutical and cosmetic industries. Being derived from natural sources, they serve as preferable alternatives to synthetic chemicals. Furthermore, they have demonstrated a wide range of therapeutic effects, including anti-inflammatory, antimicrobial, and antioxidant activities. However, the topical application of plant extracts and bioactive compounds has certain limitations, such as low skin absorption and stability. To overcome these challenges, the utilization of MEs enables enhanced skin absorption, thereby making them a valuable mode of administration. However, considering the significant surfactant content in MEs, this review evaluates the potential skin irritation caused by MEs containing herbal substances. Additionally, the review explores the topical application of MEs specifically for herbal substances, with an emphasis on their anti-inflammatory properties. Full article
(This article belongs to the Special Issue Recent Advances in Skin Drug Delivery)
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