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

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).

Grafted alginate copolymers were synthesized using butyl methacrylate (BMC) and lauryl methacrylate (LMC) at two different reaction times (12 hr and 24 hr). Copolymerization was evaluated by ¹H-NMR, Ft-IR, and TGA. Copolymer safety was examined by cytotoxicity test against HEK-293 cell. Linezolid inserts were prepared using optimized copolymers and characterized.

¹H-NMR, Ft-IR, and TGA confirmed the successful grafting of alginate copolymers. ALG-B24 and ALG-L12 showed the highest safety against HEK-293 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-B24 and ALG-L12 inserts was obtained while ALG-L12 showed a stronger adhesive force compared with intact alginate. Antibacterial efficacy on clinical isolated MRSA after 24 hr was similar to linezolid solution.

Lipophilic alginate copolymer (ALG-L12) showed a sustained release capability while retaining its main feature in strong film forming ability so it seems to be a promising safe carrier.