Depot unilamellar liposomes to sustain transscleral drug Co-delivery for ophthalmic infection therapy

Periocular routes represent a promising approach to chronic eye therapy due to its unique exploitation of scleral structure. Especially, for ophthalmic infection requiring prolonged medication, sclera-traversing dosage forms capable of co-delivery of multiple drugs are highly desirable. Herein, phosphatidylcholine-based liposomes coloading water soluble steroid dexamethasone and antibiotics moxifloxacin (LIP-DM) was developed for transscleral delivery of dual drugs. The size, mono-dispersity and drug entrapment of LIP-DM prepared by microfluidics were highly influenced by varying amounts of lipid composition. Final LIP-DM composing 63mol% phospholipid and 37mol% cholesterol was characterized of colloidal stable unilamellar structure with sub-100 nm size and entrapment of 0.412 mg and 1.21 mg for dexamethasone and moxifloxacin, respectively. Transport of LIP-DM using rabbit scleral tissues showed time-dependent particle penetration and accumulation from episcleral to intraocular side. Compared to immediate release of drugs in solution, LIP-DM exhibited differential release of dual drugs with fast antibiotics release and slow steroid release within 1 day, which in turn increased the transscleral contact time yet maintained effective permeability of dual drugs, leading to the rapid bacteriostatic onset and enhanced inhibition of proinflammatory cytokines in human retinal pigment epithelial cells. The results highlight liposomes as a potential transscleral depot of drug combination for the long-term vision care.

Automated summary

Periocular routes have great potential for the treatment of chronic eye diseases by exploiting the scleral structure. In this study, phosphatidylcholine-based liposomes (LIP-DM) were developed to deliver water-soluble steroid dexamethasone and antibiotics moxifloxacin through the sclera. The results demonstrated that LIP-DM exhibited differential release of the two drugs, with fast release of moxifloxacin and slow release of dexamethasone, leading to increased transscleral contact time and enhanced antibacterial and anti-inflammatory effects.