Novel Dexamethasone-Loaded Nanomicelles for the Intermediate and Posterior Segment Uveitis

Abstract

Abstract. Development and characterization of dexamethasone (DEX)-encapsulated polymeric nanomicelles have been reported. A low molecular weight di-block copolymer was synthesized and characterized for its structure, molecular weights, critical micelle concentration (CMC), and cytotoxicity in ocular cells. In order to delineate the effects of drug-polymer interactions on drug solubilization in micelle core, a response surface methodology was generated with the help of SAS 9.02 (exploratory model). The method for preparing micelle was modified based on the results obtained from exploratory model. The formulation was optimized by response surface methodology (optimization model) to achieve DEX solubility of above 1 mg/mL. The optimized formulation was characterized for DEX solubility, nanomicelle size, polydispersity index, surface morphology, in vitro transport across conjunctival cell line, and ex vivo transport across excised rabbit sclera. Nanomicelles exhibited average sizes in range of 25-30 nm with unimodel size distribution and low polydispersity of 0.125. Nanomicelles increased DEX permeability by 2 times across conjunctival cell line and by 2.5 times across the excised rabbit sclera as compared to DEX suspension. A design of experiment (DOE) strategy was successfully applied to understand the effects of drug-polymer interaction on drug solubility. DOE was also employed to achieve optimal formulation with high DEX solubility. Nanomicellar formulation significantly enhanced DEX permeability across the excised rabbit sclera. Therefore, nanomicellar formulation may provide therapeutic levels in the back of the eye following topical administration.

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

“…Transscleral permeability studies in excised rabbit sclera indicated a 2.5-fold increase in permeability of DEX with nanomicelles in comaprison to a DEX suspension. This study inidicated the potential of polymeric micelles in improving the bioavailability of DEX in the uvea following topical administration [128]. …”

Synthesis of three-arm block copolymer poly(lactic-<em>co</em>-glycolic acid)&ndash;poly(ethylene glycol) with oxalyl chloride and its application in hydrophobic drug delivery

“…Amphiphilic block copolymers, which possess a hydrophilic head and a hydrophobic tail, selfassemble into micelles in aqueous solution, and the hydrophobic center is achieved in this process. 3,9 These could not only be used as the delivery material of hydrophobic drugs 10 but could also be used in the delivery of hydrophilic drugs 11,12 and peptides, 13 which significantly enhance the permeability of various drugs and prolong retention.…”

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

“…5,6 This low penetration after topical application is primarily because drug entry into the ocular globe is restricted predominantly by corneal barrier functions, which serve to protect the anterior ocular segment, and by the conjunctival-scleral barrier, which 6028 li et al serves to protect the intermediate and posterior segments. 7,8 The anterior corneal barrier is composed of epithelial tight junctions and possesses unique physicochemical properties that involves the opposite characteristics of lipophilic epithelium and hydrophilic stroma. 9 The epithelium and the stroma present different physicochemical properties, and the movement of hydrophilic compounds is limited to the epithelium, whereas the movement of lipophilic compounds is limited to the stroma.…”

“…29,36 At present, there are numerous reports discussing the ocular penetration of drugs. 8,9,18,37 To the best of our knowledge, this novel biometry method was used for the first time in vivo to clearly visualize the penetration behaviors of drugs into the corneas of BALB/c mice.…”