Development and Evaluation of 5-Flucytosine Solid Lipid Nanoparticle-Loaded Topical Gels for Enhanced Chronic Wound Healing

Aug 29, 2026

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Development and evaluation of a 5-flucytosine (5-FC) solid lipid nanoparticle (SLN) gel optimized for chronic wound healing. SLNs were produced using stearic acid and poloxamer 407, optimized with central composite design, yielding particle size 390.60 nm, entrapment efficiency 89.60%, and PDI 0.215. SLNs were incorporated into a Carbopol 934 topical gel, providing drug content 94.58 ± 0.73% w/w and suitable rheology. In vitro release showed an initial burst followed by sustained delivery (91.5% at 7 h), with FTIR confirming compatibility. Biocompatibility was assessed by MTT in human fibroblasts, while in vivo diabetic mouse studies demonstrated enhanced collagen deposition, immune recruitment, and faster wound closure for localized sustained antimicrobial action.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

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Introduction

Wound healing challenges in chronic wounds

Nanotechnology and SLNs for topical delivery

Rationale for 5-flucytosine and SLN encapsulation

Abstract

Formulation design and optimization

Characterization and in vitro release

Compatibility and biocompatibility

In vivo wound healing outcomes

Journal of Pharmaceutical Innovation (2025) 20:157 [https://doi.org/10.1007/s12247-025-10063-y](https://doi.org/10.1007/s12247-025-10063-y) RESEARCH Development and Evaluation of 5-Flucytosine Solid Lipid Nanoparticle-Loaded Topical Gels for Enhanced Chronic Wound Healing Vinay Kumar Chakravarthy Maddikunta1 · Kumaraswamy Gandla2 · RajkumariThagele1 Accepted: 26 July 2025 / Published online: 2 August 2025 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025 Abstract This study aimed to develop and evaluate a 5-Flucytosine (5-FC)-loaded solid lipid nanoparticle (SLN) gel optimized for chronic wound healing. SLNs were prepared using stearic acid and poloxamer 407 and optimized via central composite design. The optimized nanoparticles exhibited a particle size of 390.60 nm, entrapment efficiency of 89.60% and PDIof 0.215. SLNs were incorporated into a Carbopol 934 gel base for topical application. The formulation demonstrated a high drug content (94.58 ± 0.73% w/w) and favorable rheological properties. In vitro drug release studies indicated an initial burst followed by sustained release (91.5% at 7 h) . FTIR confirmed drug-excipient compatibility. Biocompatibility was verified using an MTT assay in human fibroblasts. In vivo wound healing studies in diabetic mice showed enhanced collagen deposition, immune cell recruitment, and accelerated wound closure. The developed SLN-based gel presents a promising strategy for localized, sustained antimicrobial delivery in chronic wound management. Keywords 5-Flucytosine (5-FC) · Solid lipid nanoparticle · Wound healing · Topical gel · Optimization. Clinical Trial Number Not applicable. 􀀍 Kumaraswamy Gandla[drkumaraswamygandla@gmail.com](drkumaraswamygandla@gmail.com) Vinay Kumar Chakravarthy Maddikunta[m.vinay2708@gmail.com](m.vinay2708@gmail.com) Rajkumari Thagele [rajkumari.thagele@cpur.edu.in](rajkumari.thagele@cpur.edu.in) 1 Career Point University, Kota, Rajasthan, India 2 Chaitanya Deemed to be University, Gandipet, Himayathnagar, Hyderabad, India Graphical Abstract Introduction Wound healing is a dynamic and highly regulated biological process involving multiple phases, including hemostasis, inflammation, proliferation, and remodelling. Effective wound management is critical, particularly in the context of chronic wounds such as diabetic ulcers, pressure sores, and venous leg ulcers, which are often resistant to conventional treatments and remain a significant healthcare burden globally [1–3] . Chronic wounds are associated with prolonged inflammation, infection, and impaired tissue regeneration, necessitating the development of advanced therapeutic interventions. The traditional approach to wound care typically includes dressings, debridement, and topical antimicrobial agents to reduce the risk of infection. However, these methods are often inadequate in chronic wounds, where microbial infection and biofilm formation can exacerbate delayed healing [1] . Multidrug-resistant bacterial strains and fungal pathogens further complicate treatment, highlighting the need for novel drug delivery systems to provide sustained antimicrobial action while promoting tissue repair. Recent advances in nanotechnology have revolutionised drug delivery systems, offering promising alternatives for wound care [4] . Solid lipid nanoparticles (SLNs) have emerged as a versatile platform for topical drug delivery among the various nanocarrier systems. SLNs are submicron-sized particles composed of solid lipids that remain solid at room and body temperatures [3, 5, 6] . Their unique structure offers several advantages over traditional drug carriers, including improved drug stability, controlled drug release, enhanced skin penetration, and reduced systemic side effects. SLNs are particularly well-suited for topical applications due to their ability to form a lipid matrix that interacts favorably with the stratum

FAQs

What was the main objective of the study?

To develop and evaluate a 5-flucytosine (5-FC) loaded solid lipid nanoparticle gel optimized for chronic wound healing with localized, sustained antimicrobial delivery.

How were the solid lipid nanoparticles (SLNs) prepared and optimized?

SLNs were prepared using stearic acid and poloxamer 407 and optimized using a central composite design.

What did the in vitro and biocompatibility studies show?

The formulation produced sustained drug release after an initial burst (91.5% at 7 h) and FTIR confirmed drug-excipient compatibility; MTT testing in human fibroblasts supported biocompatibility.

How did the gel perform in vivo for wound healing?

In diabetic mice, the SLN-based gel enhanced collagen deposition, increased immune cell recruitment, and accelerated wound closure compared with the intended chronic wound context.

Aug 29, 2026

Uploaded by Aria