Nanoencapsulated α-Mangostin Loaded Chitosan-Alginate Hydrogel Films for Enhanced Topical Anti Acne Therapy

Nia Yuniarsih,1,2 Anis Yohana Chaerunisaa,3 Ahmed Fouad Abdelwahab Mohammed,4,5 Khaled M Elamin,6 Muchtaridi Muchtaridi,7 Nasrul Wathoni3 1Doctoral Program of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Sumedang, 45363, Indonesia; 2Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Cimahi, 40533, Indonesia; 3Department of Pharmaceutics and Pharmaceutical Technology Faculty of Pharmacy, Padjadjaran University, Sumedang, 45363, Indonesia; 4Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; 5Department of Pharmaceutics, Faculty of Pharmacy, Minia National University, New Minia, 61768, Egypt; 6Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 862-0973, Japan; 7Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang, 45363, IndonesiaCorrespondence: Nasrul Wathoni, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Sumedang, 45363, Indonesia, Tel/Fax +62-22-842-888-888, Email [email protected]: α-Mangostin (α-M) is a natural antimicrobial and anti-inflammatory compound with promising anti-acne potential; however, its poor solubility and instability limit its topical use. This study developed and evaluated chitosan-alginate hydrogel films incorporating nanoencapsulated α-M (HF α-M NPs) to enhance stability, skin penetration, and therapeutic efficacy against Propionibacterium acnes.Methods: α-M NPs were produced by ionic gelation using chitosan and sodium tripolyphosphate, followed by alginate coating, and subsequently incorporated into chitosan-alginate hydrogel films. Nanoparticles and films were characterized using SEM, FTIR, mechanical testing, swelling behavior, degradability analysis, and in vitro drug-release studies. The anti-acne performance was assessed in a P. acnes mouse model using total plate count, histopathological evaluation, and measurement of edema and erythema.Results: The nanoparticles exhibited a mean size of 229.7 ± 18.15 nm, PDI of 0.450 ± 0.046, and zeta potential of +40.9 ± 1.91 mV, indicating strong colloidal stability. SEM confirmed the uniform distribution of nanoparticle in the hydrogel matrix, while FTIR revealed molecular interactions between the polymers and α-M. HF α-M NPs showed improved mechanical strength, controlled swelling, and a sustained release profile compared with free α-M films. In vivo, the HF α-M NPs achieved the greatest reduction in P. acnes load (2.46 × 101 CFU/g), significant epithelial restoration, and the lowest edema and erythema scores, which were superior to those of free α-M and comparable to those of clindamycin gel.Conclusion: Nanoencapsulation of α-M within a chitosan-alginate hydrogel matrix significantly enhanced its stability, release behavior, and antimicrobial and anti-inflammatory effects. HF α-M NPs represents a promising antibiotic free topical therapy for acne and merits further optimization and clinical investigation.Keywords: α-mangostin, chitosan-alginate nanoparticles, hydrogel film, Propionibacterium acnes, topical delivery, anti-acne therapy