Self-assembled latanoprost loaded soluplus nanomicelles as an ophthalmic drug delivery system for the management of glaucoma

Sci Rep. 2024 Nov 7;14(1):27051. doi: 10.1038/s41598-024-78244-2.

Abstract

Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability.

Keywords: BCS class II drug; Intraocular pressure; Nanomicelles; Occular drug delivery; Particle size distribution; Soluplus.

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / pharmacokinetics
  • Antihypertensive Agents / pharmacology
  • Biological Availability
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Drug Liberation
  • Glaucoma* / drug therapy
  • Intraocular Pressure* / drug effects
  • Latanoprost* / administration & dosage
  • Latanoprost* / pharmacokinetics
  • Latanoprost* / pharmacology
  • Male
  • Micelles*
  • Nanoparticles / chemistry
  • Ophthalmic Solutions / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polyvinyls / chemistry
  • Rabbits

Substances

  • Latanoprost
  • Micelles
  • polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
  • Polyethylene Glycols
  • Polyvinyls
  • Ophthalmic Solutions
  • Antihypertensive Agents
  • Drug Carriers