Oleanolic acid nanoparticle-integrated gel: A novel topical approach for antimicrobial therapy

Abstract: Background:Topical oleanolic acid (OA) delivery is challenged by poor aqueous solubility and limited skin permeation, necessitating nanoparticle-based and bioadhesive gel systems to improve dermal retention. Objectives: This study aimed to develop and evaluate a topical gel formulation incorporating oleanolic acid nanoparticles (OANPs) to enhance the solubility and therapeutic efficacy of OA. Methods: OANPs were formulated using the nanoprecipitation technique and assessed for various physicochemical tests, whereas comprehensive gel assessment included physical appearance, pH, viscosity, spreadability and in-vitro drug release. In addition, scanning electron microscopy (SEM) analysis and an in-vivo skin irritation test were also conducted. A comparative analysis of ex-vivo drug permeation was also accomplished for free OA suspension, OANPs (F3) and OAG1. Results: The optimized OANPs (F3) maintained a mean nanoparticle size of 12.81 nm, making it more suitable for dermal application. Values of % entrapment efficiency (E.E), polydispersity index (PDI) and zeta potential were 79.18%, 0.32 ± 0.04 and -26.2 ± 1.2 mV, respectively, thus displaying maximum % EE, uniform size distribution and good colloidal stability. OANPs (F3) showed strong free-radical scavenging potential. Likewise, antimicrobial testing revealed notable zones of inhibition (ZOI) against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, confirming the effective bioactive potential. Oleanolic acid nanoparticle integrated gel formulation1(OAG1) demonstrated desirable ex-vivo drug release and permeation up to 36 h, along with no signs of irritation, redness, or lesions upon in-vivo skin irritation testing. Conclusion: OANPs were optimized, and the selected formulation (F3) was incorporated into a bioadhesive gel (OAG1) to overcome the poor aqueous solubility and limited skin permeation of OA. Both F3 and OAG1 showed comparable ex vivo drug release and permeation; however, OAG1 significantly improved OA skin retention due to its optimized viscosity, polymeric composition, improved antimicrobial action and bioadhesive properties