Sustained release of linezolid in ocular insert based on lipophilic modified structure of sodium alginate

Objective(s): Ocular inserts are usually polymeric thin films with increased ocular residence time and sustained drug release capacity. Sodium alginate is a biocompatible and biodegradable carrier; however, initial burst release of encapsulated drug within it, is recognized as a challenge. Grafting –addition of functional moieties to a polymer– is a technique to modify polymers’ physicochemical properties, including higher ability to control drug release. Linezolid (LNZ) solution is used in consecutive doses in treatment of antibiotic-resistant Gram-positive bacterial infections especially induced by methicillin resistant Staphylococcus aureus (MRSA). Materials and Methods: Grafted alginate copolymers were synthesized using butyl methacrylate (BMC) and lauryl methacrylate (LMC) at two different reaction times (۱۲ hr and ۲۴ hr). Copolymerization was evaluated by ۱H-NMR, Ft-IR, and TGA. Copolymer safety was examined by cytotoxicity test against HEK-۲۹۳ cell. Linezolid inserts were prepared using optimized copolymers and characterized.Results: ۱H-NMR, Ft-IR, and TGA confirmed the successful grafting of alginate copolymers. ALG-B۲۴ and ALG-L۱۲ showed the highest safety against HEK-۲۹۳ cell line comparing with intact alginate. Linezolid insert characterization results indicated a slower linezolid release profile related to creation of a lipophilic structure. A better strength property for linezolid loaded ALG-B۲۴ and ALG-L۱۲ inserts was obtained while ALG-L۱۲ showed a stronger adhesive force compared with intact alginate. Antibacterial efficacy on clinical isolated MRSA after ۲۴ hr was similar to linezolid solution.Conclusion: Lipophilic alginate copolymer (ALG-L۱۲) showed a sustained release capability while retaining its main feature in strong film forming ability so it seems to be a promising safe carrier.

Keywords:

Copolymer , Grafting , Linezolid , Ocular insert , Sodium alginate