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Updated: Apr 6, 2026
Generation of Alginate Microspheres for Biomedical Applications
Published on: August 12, 2012
Topical delivery of Mir-497 using cationized gelatin/sodium alginate coacervates for diabetic wound healing
Eunmi Ban1, Youngun Yu1, Yeojin Kim2,3
1College of Pharmacy, CHA University, Gyeonggi-do, Republic of Korea.
Abstract:
MicroRNA (miRNA)-based therapeutics are promising for chronic inflammatory diseases, yet their clinical translation is limited by poor stability, inefficient intracellular delivery, and safety concerns. Previously, we reported in vitro anti-inflammatory activity of miR-497 encapsulated in coacervate-based delivery platform composed of cationized gelatin (CG) and sodium alginate (SA). In the present study, we modulated the degree of CG cationization and the CG/SA weight ratio to obtain miR-497-loaded CG/SA (miR-497@CG/SA) coacervates with controlled physicochemical properties. The optimized coacervates exhibited particle sizes of approximately 250-300 nm, positive zeta potentials (+15 to + 35 mV), high transfection efficiency, and minimal cytotoxicity. Compared with binary miR-497@CG complexes, the ternary coacervates showed enhanced stability and markedly improved cellular uptake. Confocal microscopy revealed efficient endocytic internalization followed by endo-lysosomal escape into the cytosol. In high glucose-treated human dermal fibroblasts, miR-497@CG/SA significantly promoted cell migration (~1.7-fold increase) and suppressed pro-inflammatory cytokine expression (TNF-α, IL-6, and IL-1β). In a diabetic mouse wound model, topical application of freeze-dried miR-497@CG/SA coacervate sponges achieved over 80 % wound closure within 6 days, accompanied by marked suppression of inflammatory responses. Collectively, these findings demonstrate that CG/SA coacervates provide a safe, efficient, and scalable platform for miRNA delivery, highlighting their potential as a clinically relevant topical gene therapy for diabetic wound healing.
Insights
This study developed cationized gelatin/sodium alginate coacervates for efficient microRNA delivery. These coacervates improved diabetic wound healing by reducing inflammation and promoting cell migration.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Nanotechnology
Background:
- MicroRNA (miRNA)-based therapeutics show potential for chronic inflammatory diseases but face challenges in stability, delivery, and safety.
- Previous work demonstrated in vitro anti-inflammatory activity of miR-497 using a cationized gelatin (CG) and sodium alginate (SA) coacervate platform.
Purpose of the Study:
- To optimize CG/SA coacervates for controlled physicochemical properties and enhanced miR-497 delivery.
- To evaluate the efficacy of optimized miR-497-loaded coacervates (miR-497@CG/SA) in vitro and in a diabetic mouse wound model.
Main Methods:
- Modulation of CG cationization degree and CG/SA weight ratio to create miR-497@CG/SA coacervates.
- Characterization of coacervate properties including particle size, zeta potential, transfection efficiency, and cytotoxicity.
- Assessment of cellular uptake, endo-lysosomal escape, and anti-inflammatory effects in human dermal fibroblasts.
- Evaluation of wound closure and inflammatory response in a diabetic mouse model using topical coacervate sponges.
Main Results:
- Optimized miR-497@CG/SA coacervates exhibited particle sizes of 250-300 nm, positive zeta potentials (+15 to +35 mV), high transfection efficiency, and low cytotoxicity.
- Ternary coacervates demonstrated enhanced stability and cellular uptake compared to binary complexes, with efficient cytosolic delivery.
- In vitro, miR-497@CG/SA promoted human dermal fibroblast migration and suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β).
- Topical application of freeze-dried miR-497@CG/SA sponges resulted in over 80% wound closure in diabetic mice within 6 days, with reduced inflammation.
Conclusions:
- CG/SA coacervates represent a safe, efficient, and scalable platform for miRNA delivery.
- This platform holds significant potential for topical gene therapy applications, particularly in accelerating diabetic wound healing.
- Further development of these coacervates could overcome current limitations in miRNA-based therapeutics for inflammatory conditions.
