Advanced Biomaterial for Dual-Drug Release: A Hydrogel-Microparticle Approach

Abstract

Advanced biomaterials with dual drug delivery represent a promising strategy to enhance therapeutic outcomes in wound treatment. This work aimed to combine antimicrobial and analgesic actions in a single platform, enabling the simultaneous release of both drugs from an advanced dual-drug delivery system based on a combined hydrogel and microparticle approach. The system was composed of alginate microparticles containing the antibiotic gentamicin incorporated into a gellan gum/collagen hydrogel matrix, in which the local anesthetic bupivacaine was directly loaded. The resulting composite was thoroughly characterized in terms of its morphological, physicochemical, mechanical, rheological, and thermal properties, as well as drug release profiles. The incorporation of microparticles significantly influenced the structural and functional behavior of the hydrogel, particularly at higher microparticle concentrations (50% w/v). Notably, the microparticles played a crucial role in maintaining the hydrogel's integrity in the presence of both drugs and enabled their controlled and simultaneous release, with each exhibiting distinct release kinetics. These findings highlight the potential of this hydrogel and microparticle composite as an advanced material for wound dressings, capable of promoting healing while simultaneously providing localized pain relief.

Keywords: biopolymers; controlled release; dual‐drug delivery; hydrogel; microparticles; polysaccharides; wound healing.

FIGURE 1

Schematic representation of the methodology used to prepare the dual‐drug delivery systems. (A) Preparation of alginate microparticles loaded with gentamicin, (B) preparation of gellan gum/collagen hydrogels loaded with bupivacaine, and (C) preparation of the dual‐drug delivery system.

FIGURE 2

(A) Optical microscopy and (B) scanning electron microscopy micrographs of the alginate microparticles.

FIGURE 3

Photographs and SEM micrographs of gellan gum/collagen hydrogels without and with adding different concentrations of alginate microparticles (MP).

FIGURE 4

Elastic (G′) and viscous (G″) moduli and the crossover point of formation of hydrogels upon cooling gellan gum/collagen solutions with and without alginate microparticles. (A) Hydrogel without microparticle, (B) 0.5%, (C) 2.5%, (D) 5%, (E) 25% and (F) 50% w/v microparticles added in the hydrogel. Filled symbols represent G′ and open symbols represent G″.

FIGURE 5

Infrared spectra of microparticles and hydrogels without and with adding microparticles.

FIGURE 6

(A) Thermograms obtained by differential calorimetry (DSC) and (B) TGA and DTGA thermograms of microparticles and gellan gum/collagen hydrogels without and with adding alginate microparticles.

FIGURE 7

Kinetic curves for the release of gentamicin from microparticles (MP(GEN)) and dual‐drug delivery system (H‐MP(GEN)), and the release of bupivacaine from hydrogels (H(BPV)) and dual‐drug delivery system (H(BPV)‐MP).

FIGURE 8

Fitting of mathematical models to the kinetic data of the release of drugs present in (A) hydrogels, (B) microparticles, (C, D) dual‐drug delivery systems.