Novel ultra-small micelles based on ginsenoside Rb1: a potential nanoplatform for ocular drug delivery

Objectives: Ginsenosides Rb1 (Rb1) could form micelles in aqueous solutions. Self-assembled Rb1 micelles could potentially be utilized as ocular drug delivery system, and it was postulated that the encapsulation of a medicine within Rb1 micelles might strengthen the drug’s therapeutic action and reduce side effects. Methods: Diclofenac-loaded Rb1 micelles (Rb1-Dic micelles) were formulated, optimized, and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vivo corneal permeation, and in vivo anti-inflammatory efficacy. Results: Rb1 self-assembled into micelles with ultra-small particle size (<8 nm) in a homogeneous distribution state (polydispersity index [PDI] < 0.3). Diclofenac was highly encapsulated into the micelles according to the weight ratios of Rb1 to diclofenac. The ophthalmic solution of Rb1-Dic micelle was simple to prepare. Rb1 had good cellular tolerance, and it also improved the cellular tolerance of the encapsulated diclofenac. Rb1-Dic micelles also showed non-irritants to the rabbit eyes. The use of Rb1 micelles significantly improved the in vivo corneal permeation as well as the anti-inflammatory efficacy of diclofenac when compared to commercial diclofenac eye drops. Conclusion: Rb1 micelle formulations have great potential as a novel ocular drug delivery system to improve the bioavailability of drugs such as diclofenac.