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Pharmaceuticals
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Advances in Topical and Mucosal Drug Delivery Systems
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Advances in Topical and Mucosal Drug Delivery Systems

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

Deadline for manuscript submissions: 25 September 2026 | Viewed by 8823

Special Issue Editor

Prof. Dr. Michelle Franz-Montan

E-Mail Website
Guest Editor
Department of Biosciences, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba 13083-970, SP, Brazil
Interests: topical anesthesia; oral cavity; oral mucosa; dental anesthesia; drug delivery; mucoadhesive system; dentistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Topical and mucosal routes offer localized drug delivery pathways, minimizing systemic side effects and maximizing therapeutic efficacy at the target site. Significant advancements in materials science and formulation technologies have recently broadened the application of these routes across diverse therapeutic areas.

This Special Issue aims to showcase the latest innovations in topical and mucosal drug delivery systems, covering formulation design, novel materials, and targeted delivery strategies. Emerging areas such as micro/nano-particulate delivery, microneedles, and stimuli-responsive gels are revolutionizing topical and mucosal therapeutics. These advancements offer the potential for controlled release, enhanced penetration, and improved therapeutic outcomes.

We invite original research articles, reviews, and short communications detailing novel approaches to topical and mucosal drug delivery.

Prof. Dr. Michelle Franz-Montan
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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. Pharmaceuticals 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
  • mucosal drug delivery
  • transdermal drug delivery
  • controlled release
  • bioavailability enhancement
  • formulation development

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Published Papers (5 papers)

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Research

16 pages, 2614 KB  
Article
Comprehensive Evaluation of a Mucoadhesive Self-Emulsifying Anhydrous Base for Vaginal Drug Delivery
by Guiyun Song, Yi Liu, Kendice Ip, Ashley Shan, Christine Vu, Kateryna Khokhlova, Oleksandr Zdoryk, Maria Carvalho and Daniel Banov
Pharmaceuticals 2026, 19(4), 585; https://doi.org/10.3390/ph19040585 - 7 Apr 2026
Viewed by 514
Abstract
Background/Objectives: Compounded vaginal creams are widely used for conditions such as hormone replacement therapy, vaginal dryness, low libido, vaginal infections, etc. Recent research highlights the potential of using anhydrous bases to extend shelf life, particularly when combined with self-emulsifying and mucoadhesive properties [...] Read more.
Background/Objectives: Compounded vaginal creams are widely used for conditions such as hormone replacement therapy, vaginal dryness, low libido, vaginal infections, etc. Recent research highlights the potential of using anhydrous bases to extend shelf life, particularly when combined with self-emulsifying and mucoadhesive properties that improve mucosal retention and enhance drug bioavailability. This study provides in vitro and ex vivo evaluation of an anhydrous vaginal base. Methods: Key quality indicators such as irritation potential, leakage potential, pH compatibility, mucoadhesion, and self-emulsification were assessed using the chorioallantoic membrane Hen’s Egg Test, MTT assay, texture analysis, and fluorescence microscopy. Results: The anhydrous vaginal base demonstrated high cell viability (>78%) and non-irritant potential (IS = 2.5) in in vitro assays. It maintained physiological vaginal pH (4.56 ± 0.05), showed strong mucoadhesive properties comparable to commercial products, and exhibited minimal leakage. Ex vivo studies confirmed its prolonged retention on vaginal tissues. The anhydrous vaginal base formed stable emulsions upon contact with vaginal fluid simulant, effectively distributing both lipophilic and hydrophilic compounds. Conclusions: Compared to water-containing bases, an anhydrous vaginal base shows advantages: longer retention time and lower leakage; adaptability to varying vaginal fluid levels; and efficient dispersion of both hydrophilic and lipophilic active pharmaceutical ingredients. These features support its potential use in compounded vaginal products, minimizing stability risks and enhancing patient compliance and therapeutic outcomes. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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17 pages, 1817 KB  
Article
Topical Delivery of Autochthonous Lactic Acid Bacteria Using Calcium Alginate Microspheres as a Probiotic Carrier System with Enhanced Therapeutic Potential
by Sigita Jeznienė, Emilija Mikalauskienė, Aistė Jekabsone and Aušra Šipailienė
Pharmaceuticals 2026, 19(1), 66; https://doi.org/10.3390/ph19010066 - 29 Dec 2025
Viewed by 526
Abstract
Background/Objectives: Three distinct strains of lactic acid bacteria (LAB), isolated from naturally fermented bread sourdough and representing the local autochthonous microflora, were selected to evaluate their potential probiotic properties. In addition, we evaluated whether these strains could be used in topical formulations. Methods: [...] Read more.
Background/Objectives: Three distinct strains of lactic acid bacteria (LAB), isolated from naturally fermented bread sourdough and representing the local autochthonous microflora, were selected to evaluate their potential probiotic properties. In addition, we evaluated whether these strains could be used in topical formulations. Methods: We evaluated probiotic properties such as the ability to co-aggregate with pathogens, antimicrobial activity, inhibition of pathogenic biofilms, and ability to adhere to human keratinocyte cells. Further, bacteria were encapsulated in calcium alginate microspheres using the emulsification/external gelation method, and their viability in topical formulations was assessed. Results: LAB significantly inhibited biofilm formation by the tested pathogens with complete inhibition observed in certain cases. The strength and specificity of these probiotic effects varied depending on the LAB strain and the target pathogen. Furthermore, among the tested strains, L. reuteri 182 exhibited the highest adhesion rates, reaching 77.94 ± 1.84%. In the context of potential topical applications, the preservative present in the formulation completely inactivated the planktonic cells of L. reuteri 182. In contrast, encapsulation within a biopolymeric system conferred protection against the preservative’s bactericidal effect. After 35 days of storage at room temperature, viable cell counts reached 5.94 ± 0.06 lg CFU/g. Conclusions: Our findings confirm that local LAB strains, specifically L. reuteri 182 and L. plantarum F1, possess essential probiotic characteristics and can be effectively incorporated into preservative-containing topical formulations via efficient encapsulation strategies. This underscores the potential of these topical probiotics for skin health and highlights the need for clear regulatory guidance to ensure their safe and effective application. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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30 pages, 4770 KB  
Article
Formulation and Characterization of Oxiconazole-Loaded Novasomes to Enhance the Treatment of Fungus Infections: Experimentally Induced Candidiasis in Rat
by Ibrahim A. Mousa, Abdelghafar M. Abu-Elsaoud, Shereen A. Sabry, Mahmoud Abd Elghany, Dina Khodeer, Fathy E. Abdelgawad and Ali M. Nasr
Pharmaceuticals 2025, 18(12), 1803; https://doi.org/10.3390/ph18121803 - 26 Nov 2025
Viewed by 957
Abstract
Background/Objectives: An observed increase in fungal infection incidence over the past two decades underscores the limitations of conventional topical treatments for deep infections, primarily due to the skin’s stratum corneum barrier. This has driven the development of advanced topical preparations. This study [...] Read more.
Background/Objectives: An observed increase in fungal infection incidence over the past two decades underscores the limitations of conventional topical treatments for deep infections, primarily due to the skin’s stratum corneum barrier. This has driven the development of advanced topical preparations. This study evaluated the encapsulation of oxiconazole utilizing novasomes to enhance its topical delivery. Methods: Oxiconazole-loaded novasomes were synthesized by the ethanol injection technique and subsequently characterized using key physicochemical parameters, including encapsulation efficiency (EE%), vesicle size (VS), zeta potential (ZP), polydispersity index (PDI), and percentage drug release (DR%). The optimized formulation underwent comprehensive evaluation employing Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Moreover, its activity was evaluated through in vitro penetration studies and in vivo assessments. Results: R9 was identified as the optimal candidate, demonstrating an encapsulation efficiency of 94.63 ± 1.60%, a vesicle size of 174 ± 1.15 nm, a zeta potential of −46.5 ± 1.61 mV, a polydispersity index of 0.184 ± 0.01, and a drug release rate of 51 ± 0.50% within 8 h. This optimal formula achieved 94 ± 1.75% permeation of oxiconazole within 24 h. FTIR examination affirmed the interaction of oxiconazole and the excipients, while DSC analysis verified the thermal durability of oxiconazole. In vivo histopathological examination demonstrated the superior efficacy of the optimal formula in treating Candida albicans infection. Conclusions: Novasomes emerge as a promising and efficacious system for oxiconazole encapsulation, holding significant potential for the effective and prolonged management of topical fungal infections. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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26 pages, 3940 KB  
Article
In Vitro Proof-of-Concept Study: Lidocaine and Epinephrine Co-Loaded in a Mucoadhesive Liquid Crystal Precursor System for Topical Oral Anesthesia
by Giovana Maria Fioramonti Calixto, Aylla Mesquita Pestana, Arthur Antunes Costa Bezerra, Marcela Tavares Luiz, Jonatas Lobato Duarte, Marlus Chorilli and Michelle Franz-Montan
Pharmaceuticals 2025, 18(8), 1166; https://doi.org/10.3390/ph18081166 - 6 Aug 2025
Viewed by 3007
Abstract
Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and [...] Read more.
Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and characterized a novel lidocaine and epinephrine co-loaded liquid crystalline precursor system (LCPS) for topical anesthesia. The formulation was structurally characterized using polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological behavior was assessed through continuous and oscillatory rheological analyses. Texture profile analysis, in vitro mucoadhesive force evaluation, in vitro drug release and permeation studies, and an in vivo toxicity assay using the chicken chorioallantoic membrane (CAM) model were also conducted. Results: PLM and SAXS confirmed the transition of the LCPS from a microemulsion to a lamellar liquid crystalline structure upon contact with artificial saliva. This transition enhanced formulation consistency by over 100 times and tripled mucoadhesion strength. The LCPS also provided controlled drug release, reducing permeation flow by 93% compared to the commercial formulation. Importantly, the CAM assay indicated that the LCPS exhibited similar toxicity to the commercial product. Conclusions: The developed LCPS demonstrated promising physicochemical and biological properties for topical anesthesia, including enhanced mucoadhesion, controlled drug delivery, and acceptable biocompatibility. These findings support its potential for in vivo application and future clinical use to reduce pain during dental anesthesia procedures. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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35 pages, 8014 KB  
Article
Chitosan Nanoparticles for Topical Drug Delivery in Chemotherapy-Induced Alopecia: A Comparative Study of Five Repurposed Pharmacological Agents
by Salma A. Fereig, John Youshia, Ghada M. El-Zaafarany, Mona G. Arafa and Mona M. A. Abdel-Mottaleb
Pharmaceuticals 2025, 18(7), 1071; https://doi.org/10.3390/ph18071071 - 21 Jul 2025
Cited by 2 | Viewed by 3003
Abstract
Background/Objectives: Chemotherapy-induced alopecia is a common and distressing side effect of cancer treatment, significantly impacting patients’ psychological well-being. Nanocarriers offer a promising strategy for targeted drug delivery to hair follicles, while chitosan nanoparticles have demonstrated hair-growth-promoting properties. This study explores the potential [...] Read more.
Background/Objectives: Chemotherapy-induced alopecia is a common and distressing side effect of cancer treatment, significantly impacting patients’ psychological well-being. Nanocarriers offer a promising strategy for targeted drug delivery to hair follicles, while chitosan nanoparticles have demonstrated hair-growth-promoting properties. This study explores the potential of chitosan nanoparticles as a topical delivery system for five pharmacological agents—phenobarbital, pioglitazone, rifampicin, N-acetylcysteine, and tacrolimus—to prevent chemotherapy-induced alopecia. Methods: Drug-loaded chitosan nanoparticles were prepared using the ionic gelation technique and characterized by particle size, zeta potential, entrapment efficiency, FT-IR spectroscopy, and TEM imaging. Their efficacy was assessed in a cyclophosphamide-induced alopecia model in C57BL/6 mice through macroscopic observation, histopathological examination, and scanning electron microscopy of regrown hair. Results: The prepared particles were spherical, cationic, and between 205 and 536 nm in size. The entrapment efficiencies ranged from 8% to 63%. All five drugs mitigated follicular dystrophy, shifting the hair follicle response from dystrophic catagen to dystrophic anagen. Phenobarbital demonstrated the most significant hair regrowth and quality improvements, followed by N-acetyl cysteine and pioglitazone. Tacrolimus showed moderate efficacy, while rifampicin was the least effective. Conclusions: These findings suggest that phenobarbital-loaded chitosan nanoparticles represent a promising approach for the prevention and treatment of chemotherapy-induced alopecia, warranting further investigation for clinical applications. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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