Chitosan and carboxymethylchitosan nanoparticle-based mupirocin hydrogel system for improved wound healing

Abstract

Mupirocin hydrogel system comprising chitosan and carboxymethyl chitosan nanoparticles for sustained drug release and improved wound healing.

Description

AREA OF INVENTION

[0001] The present invention relates to biomedical and pharmaceutical delivery systems, in particular a nanoparticle-based hydrogel formulation for effective wound healing through sustained mupirocin release, improved penetration and antimicrobial protection. BACKGROUND OF THE INVENTION

[0002] Wound healing is a complex biological process requiring efficient infection control, tissue regeneration, and the maintenance of a moist wound environment. Conventional wound treatments, such as antibiotic creams and ointments, often reach their limits, including poor skin penetration, rapid drug degradation, and the need for frequent applications. Mupirocin, a topical antibiotic effective against Staphylococcus aureus and Streptococcus, is commonly used for bacterial skin infections; however, its limited solubility and permeability restrict its therapeutic efficacy. To address these challenges, researchers have investigated nanoparticle-based delivery systems using biopolymers such as chitosan and carboxymethyl chitosan, both known for their biodegradability, biocompatibility, and inherent antimicrobial properties.Chitosan offers excellent film-forming and wound-adherent properties, while carboxymethyl chitosan improves water solubility and drug loading. However, nanoparticle suspensions alone are difficult to apply and do not provide long-term adhesion to wounds. Embedding such nanoparticles in a hydrogel matrix can ensure prolonged contact, sustained drug release, and improved wound healing outcomes. The present invention thus provides a novel nanoparticle-based hydrogel system that combines the therapeutic advantages of mupirocin, chitosan, and carboxymethyl chitosan in a single, optimized wound-healing formulation. SUMMARY OF THE INVENTION

[0003] The present invention describes a hydrogel system based on chitosan and carboxymethyl chitosan nanoparticles loaded with mupirocin that promotes wound healing. The system integrates biocompatible polymers with mupirocin in nanoparticle form, which are then embedded in a hydrogel matrix. This enables sustained drug release, improved dermal penetration, and prolonged antimicrobial activity. The invention overcomes the limitations of conventional formulations by ensuring prolonged drug retention in the wound area and preventing the recurrence of infections, thereby promoting faster healing.

[0004] The process involves the production of mupirocin-loaded nanoparticles by ionic gelation of chitosan and carboxymethyl chitosan under optimized conditions, followed by embedding in a hydrogel base. Formulation parameters such as polymer ratio, emulsifier concentration, and homogenization rate are optimized using a central composite experimental design to achieve high encapsulation efficiency and stability. The resulting hydrogel is transparent, pH-compatible, and continuously releases mupirocin over 24 hours. The invention provides a simple, environmentally friendly, and effective wound care system suitable for biomedical applications. DETAILED DESCRIPTION OF THE INVENTION

[0005] The invention relates to a novel, hydrogel-based drug delivery system for topical wound healing. The formulation is based on the encapsulation of mupirocin, an antibacterial agent, in chitosan and carboxymethyl chitosan nanoparticles, which are subsequently dispersed in a hydrogel base to create a semi-solid, biocompatible matrix. The nanoparticles are synthesized by ionic gelation, with chitosan and carboxymethyl chitosan being dissolved separately in dilute acetic acid and deionized water, respectively. Mupirocin is added to the polymer solution, followed by the dropwise addition of a crosslinking agent such as sodium tripolyphosphate (TPP) with continuous stirring to form uniform nanoparticles.

[0006] The resulting nanoparticle suspension is purified by centrifugation and filtration through a 0.22 µm membrane to remove unbound drug and impurities. The purified nanoparticles are embedded in a hydrogel matrix of carbopol or hydroxypropyl methylcellulose, the pH of which is adjusted to a physiological value suitable for topical application. The hydrogel serves as a reservoir for the controlled release of mupirocin, improving skin penetration and maintaining an optimal wound environment. The formulation is optimized using a central composite design (CCD) in which variables such as polymer ratio, emulsifier concentration, and stirring speed are systematically varied. The optimized batch exhibits maximum encapsulation efficiency and consistent drug release kinetics.Analytical methods such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) confirm the absence of chemical interactions between mupirocin and polymers, thus demonstrating the stability of the formulation. The physicochemical properties of the hydrogel, such as spreadability, viscosity, homogeneity, and transparency, are evaluated to ensure its suitability for dermal application. In vitro release studies show a sustained mupirocin release of approximately 86.59% within 24 hours, following a diffusion-controlled mechanism. The biopolymer-based matrix not only improves the stability and bioavailability of mupirocin but also supports wound moisture balance and provides an inherent antimicrobial effect thanks to the chitosan derivatives it contains.

[0007] Further antimicrobial in-vitro tests confirm the efficacy of the developed hydrogel against gram-positive and gram-negative bacteria, with significant zones of inhibition comparable to those of commercially available mupirocin ointments. The hydrogel also promotes wound closure and tissue regeneration by maintaining a moist healing environment and preventing microbial colonization. The system's transparency allows for real-time wound monitoring, and its non-greasy consistency ensures better patient compliance.

[0008] The developed formulation thus represents an integrated nanoparticle-hydrogel system that offers improved mupirocin release, superior antimicrobial efficacy, and enhanced wound healing capacity. The process is scalable, cost-effective, and environmentally friendly, and is therefore suitable for the industrial production of next-generation wound care materials.

Claims

[1] Mupirocin hydrogel system comprising chitosan and carboxymethyl chitosan nanoparticles for sustained drug release and improved wound healing. [2] Hydrogel system according to claim 1, wherein mupirocin is encapsulated in chitosan and carboxymethyl chitosan nanoparticles synthesized by ionic gelation and incorporated into a hydrogel base. [3] Hydrogel system according to claim 1, wherein the formulation enables sustained mupirocin release for up to 24 hours with high encapsulation efficiency and biocompatibility. [4] Hydrogel system according to claim 1, wherein the developed hydrogel has superior antimicrobial, moisturizing and wound-healing properties and is suitable for clinical and pharmaceutical applications.