Biocompatible Polymeric Nanoparticles for Potential Application in Antimicrobial Skin Regeneration Therapies

Abstract

Severe injuries can compromise the healing process, leading to infections and complications. Bioengineered artificial skin substitutes (BASS) are used for treating extensive burns, but infections, particularly by Pseudomonas aeruginosa (P. aeruginosa), are a significant challenge.

Highlights

Colistin-loaded PLGA nanoparticles were successfully formulated and characterized.

Biocompatibility of nanoparticles was shown in fibroblasts and skin substitutes.

Colistin release was pH-dependent, enabling controlled antibiotic delivery.

Antibiotic nanoparticles-loaded skin substitutes exhibited antibacterial activity.

This approach represents a promising strategy for advanced wound care applications.

This study developed a new wound care approach by combining the healing properties of BASS with the antimicrobial effectiveness of antibiotic nanoparticles (NPs) in a loaded BASS formulation. Chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA) NPs were formulated using ion gelation and double emulsion methods.

The mean diameter, size distribution, surface charge, and stability of colloids were characterized. The biocompatibility of NPs on human fibroblast and BASS was assessed through proliferation, metabolic assays, and histological and immunohistochemical analyses. The encapsulation efficiency of colistin (COL) was evaluated, and its release from PLGA NPs was assessed. COL-loaded PLGA NPs were incorporated into BASS, and the microstructure and antimicrobial efficacy against P. aeruginosa were studied. Results showed the successful formulation of CS and PLGA NPs, with only the latter encapsulating COL.

The release of COL from PLGA NPs occurred under acidic conditions in a sustained manner. The incorporation of NPs inside the BASS slightly inhibited bacterial growth. In conclusion, antibiotic NPs-loaded BASS represents a promising strategy for clinical applications. This is relevant in reconstructive surgery for skin defects, as skin pH typically remains around 5.5, and in treating wounds with different pH levels, like chronic and severe wounds. In these cases, the gradual decrease in pH as the wound heals could facilitate controlled antibiotic release.

Materials

All chemicals used in this study were of analytical grade and employed without further

Formulation of blank drug unloaded and COL-loaded PLGA and CS NPs

Blank CS NPs were prepared using the ionic gelation method as previously described [22] with some modifications. Briefly, the low MW CS was dissolved in a solution of glacial acetic acid containing 0.5% (w/v) Kolliphor at a concentration of 2 mg/mL. This solution was stirred magnetically until completely homogenized, and the pH was adjusted to 5 using a 0.5 M NaOH solution. TPP was prepared by dissolving it in water at a concentration of 2 mg/mL under magnetic stirring, and the pH was adjusted

Characteristics and biocompatibility of blank CS and PLGA NPs

Characteristics of the PLGA and CS NPs are compiled in Table 1 (at day zero). Mean diameter of the PLGA particles and CS particles were ≈ 180 nm and ≈ 290 nm, respectively. Additionally, size distribution of both polymeric NPs could be considered adequately homogeneous, given their PdI values: ≈ 0.164 for PLGA particles and ≈ 0.229 for CS particles. HRTEM images confirmed the small size of the NPs and allowed to visualize their spherical shape (Figure 1). Finally, these reproducible

María I. Quiñones-Vico, Inmaculada Mulero-Valle, Ana Ubago-Rodríguez, Ana Fernández-González, Fátima Fernández-Álvarez, José L. Arias, José Gutiérrez-Fernández, Salvador Arias-Santiago, Biocompatible Polymeric Nanoparticles for Potential Application in Antimicrobial Skin Regeneration Therapies, Journal of Drug Delivery Science and Technology, 2025, 107583, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107583.

See also our CPhI Frankfurt overview article:

Tags: excipients formulation

Biocompatible Polymeric Nanoparticles for Potential Application in Antimicrobial Skin Regeneration Therapies

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