Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures

Abstract

Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameters and extend the drug pharmacological action. Self-assembled nanostructures were prepared using a modified thin-film hydration technique. The formulae compositions were designed based on response surface statistical design. The prepared self-assembled nanostructures were characterized by testing their drug content, particle size, polydispersity index, zeta potential, partition coefficient, release half-life and extent. The optimized formulae having the highest drug content, zeta potential, partition coefficient, release half-life and extent with the lowest particle size and polydispersity index were subjected to further investigations including investigation of their physicochemical, morphological characteristics, in vivo pharmacokinetic and pharmacodynamic profiles. The optimized formulae were prepared at pH 8.7 (F5 and F6) and composed of L-α-Phosphatidylcholine and drug mixed in a ratio of 1:1 and 2:1 w/w, respectively. They showed significantly higher Cmax, and at the aqueous humor with extended control over the intra-ocular pressure, when compared to the marketed product; Trusopt®. The study introduced novel and promising self-assembled formulae able to permeate higher drug amount through the cornea and achieve sustained pharmacological effect at the site of action.

Breaking Barriers in Eye Treatment: Polymeric Nano-Based Drug-Delivery System for Anterior Segment Diseases and Glaucoma

“…Other notable DDS systems include self-assembly drug nanostructures (SADN) [ 87 ] and phase transition microemulsions (PMEs) [ 88 ] which are both novel systems that aided in sustained IOP-lowering effect. Cytotoxicity and systemic effects remain to be investigated for both delivery systems.…”

New technologies of hypotensive drug delivery in glaucoma treatment

“…Многим исследователям представляется перспективным для доставки гипотензивных препаратов использовать комбинации полимеров и коллоидных систем: липосом [22][23][24][25][26], ниосом [27,28], кубосом [29], микроэмульсий [30], наноэмульсий [31][32][33] и наночастиц [34][35][36][37][38][39][40]. За счет медленного высвобождения лекарственных препаратов удается значительно пролонгировать время нахождения активного вещества в глазу.…”

Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma

“…To overcome these inconveniences and also the side effects generated by the administration of free drugs, different types of carriers, including hydrogels, nanoparticles, nanoemulsions, liposomes, and micelles, have been investigated in order to increase the ocular permeability of drugs, thus providing enhanced ocular drug bioavailability by increasing the corneal contact time [ 10 , 11 , 12 , 13 , 14 , 15 ].…”