Progress in the design of chitosan-based nanogels for folic acid delivery for ocular applications.

Diego A Chiappetta, Sebastián G Bruno, Agustina Alaimo, Cecilia Samaniego López, Alejandra J Rubinstein, Sergio I Nemirovsky, Marcela A Moretton, Oscar E Pérez

Journal: International journal of biological macromolecules 2025;318(Pt 2):145053

PMID: 40499857

Full Text on Elsevier Science View on PubMed

Abstract

Folic acid (FA) plays a vital role in cellular metabolism, DNA and RNA synthesis, and antioxidant defences. However, FA's bioavailability is limited due to its susceptibility to environmental agents and physiological conditions, making essential an effective protection system. In this context, Nanogels (NG) were developed for FA ophthalmic delivery using ionic gelation with chitosan (CS) and tripolyphosphate (TPP) in different mass ratios. The optimized formulation, selected based on experimental design, consisted of 2.25 mg/mL CS and 0.75 mg/mL TPP. For an initial FA concentration of 300 μM, the encapsulation efficiency was 81%. NG FA-300 formulation displayed a monodisperse size of 222 nm, low polydispersity (0.30), and a ζ-potential of +24.9 mV. TEM and AFM analyses showed spheroid particles with low height with rough surface. In vitro release profile of FA from the NG described a first-order kinetics under simulated tear fluid. ABTS assays confirmed that FA retained antioxidant activity within the NG. Biocompatibility tests showed no cytotoxicity to ARPE-19 cells, with efficient internalization visualized by FITC-NG and avoidance of endo-lysosomal degradation. FA into NG did not alter its biological activity and helped to mitigate oxidative stress in cells. CS NG are promising vehicles for FA delivery for ocular applications.

Address: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina. Electronic address: [email protected].; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales - Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIBICEN-CONICET), Buenos Aires, Argentina. Electronic address: [email protected].; Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales - Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIBICEN-CONICET), Buenos Aires, Argentina. Electronic address: [email protected].; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales - Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIBICEN-CONICET), Buenos Aires, Argentina. Electronic address: [email protected].; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales - Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIBICEN-CONICET), Buenos Aires, Argentina. Electronic address: [email protected].; Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Buenos Aires, Argentina. Electronic address: [email protected].; Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Buenos Aires, Argentina. Electronic address: [email protected].; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales - Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIBICEN-CONICET), Buenos Aires, Argentina. Electronic address: [email protected].

DOI: 10.1016/j.ijbiomac.2025.145053

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MeSH Terms: Chitosan, Folic Acid, Humans, Nanogels, Antioxidants, Cell Line, Drug Carriers, Drug Liberation, Drug Delivery Systems, Polyphosphates