Design of ophthalmic micelles loaded with diclofenac sodium: effect of chitosan and temperature on the block-copolymer micellization behaviour
Journal
Drug Delivery and Translational Research
Date Issued
2022-06-01
Author(s)
Koummich, Sarra Aicha
Zoukh, Ikram Mustapha
Gorachinov, Filip
Geskovski, Nikola
Dodov, Marija Glavas
Goracinova, Katerina
DOI
10.1007/s13346-021-01030-4
Abstract
TY - JOUR
AU - Koummich, Sarra Aicha
AU - Zoukh, Ikram Mustapha
AU - Gorachinov, Filip
AU - Geskovski, Nikola
AU - Makreski, Petre
AU - Dodov, Marija Glavas
AU - Goracinova, Katerina
PY - 2022
DA - 2022/06/01
TI - Design of ophthalmic micelles loaded with diclofenac sodium: effect of chitosan and temperature on the block-copolymer micellization behaviour
JO - Drug Delivery and Translational Research
SP - 1488
EP - 1507
VL - 12
IS - 6
AB - Diclofenac sodium 0.1% is a commonly used NSAID with well-documented clinical efficacy in reducing postoperative inflammation; however, its corneal tolerability and ophthalmic tissue bioavailability require further improvement. Advanced micellar delivery systems composed of block-copolymers and chitosan showing fine balance between the mucoadhesion and mucus permeation, capable to slip through the mucus barrier and adhere to the epithelial ocular surface, may be used to tackle both challenges. The aggregation behaviour of the block-copolymers in the presence of different additives will dramatically influence the quality attributes like particle size, particle size distribution, drug-polymer interaction, zeta potential, drug incorporation, important for the delicate balance among mucoadhesion and permeation, as well as safety and efficacy of the ophthalmic micelles. Therefore, quality by design approach and D-optimal experimental design model were used to create a pool of useful data for the influence of chitosan and the formulation factors on the block copolymer’s aggregation behaviour during the development and optimization of Diclofenac loaded Chitosan/Lutrol F127 or F68 micelles. Particle size, polydispersity index, dissolution rate, FTIR and DSC studies, NMR spectroscopy, cytotoxicity, mucoadhesivity, mucus permeation studies, and bioadhesivity were assessed as critical quality attributes. FTIR and DSC studies pointed to the chaotropic effect of chitosan during the micelle aggregation. Mainly, Pluronic F68 micellization behaviour was more dramatically affected by the presence of chitosan, and self-aggregation into larger micelles with high polydispersity index was favoured at higher chitosan concentration. The optimized formulation with highest potential for ophthalmic delivery of diclofenac sodium, good cytotoxicity profile, delicate balance of the mucoadhesivity, and mucus permeation was in the design space of Chitosan/Lutrol F127 micelles.
SN - 2190-3948
UR - https://doi.org/10.1007/s13346-021-01030-4
DO - 10.1007/s13346-021-01030-4
ID - Koummich2022
ER -
AU - Koummich, Sarra Aicha
AU - Zoukh, Ikram Mustapha
AU - Gorachinov, Filip
AU - Geskovski, Nikola
AU - Makreski, Petre
AU - Dodov, Marija Glavas
AU - Goracinova, Katerina
PY - 2022
DA - 2022/06/01
TI - Design of ophthalmic micelles loaded with diclofenac sodium: effect of chitosan and temperature on the block-copolymer micellization behaviour
JO - Drug Delivery and Translational Research
SP - 1488
EP - 1507
VL - 12
IS - 6
AB - Diclofenac sodium 0.1% is a commonly used NSAID with well-documented clinical efficacy in reducing postoperative inflammation; however, its corneal tolerability and ophthalmic tissue bioavailability require further improvement. Advanced micellar delivery systems composed of block-copolymers and chitosan showing fine balance between the mucoadhesion and mucus permeation, capable to slip through the mucus barrier and adhere to the epithelial ocular surface, may be used to tackle both challenges. The aggregation behaviour of the block-copolymers in the presence of different additives will dramatically influence the quality attributes like particle size, particle size distribution, drug-polymer interaction, zeta potential, drug incorporation, important for the delicate balance among mucoadhesion and permeation, as well as safety and efficacy of the ophthalmic micelles. Therefore, quality by design approach and D-optimal experimental design model were used to create a pool of useful data for the influence of chitosan and the formulation factors on the block copolymer’s aggregation behaviour during the development and optimization of Diclofenac loaded Chitosan/Lutrol F127 or F68 micelles. Particle size, polydispersity index, dissolution rate, FTIR and DSC studies, NMR spectroscopy, cytotoxicity, mucoadhesivity, mucus permeation studies, and bioadhesivity were assessed as critical quality attributes. FTIR and DSC studies pointed to the chaotropic effect of chitosan during the micelle aggregation. Mainly, Pluronic F68 micellization behaviour was more dramatically affected by the presence of chitosan, and self-aggregation into larger micelles with high polydispersity index was favoured at higher chitosan concentration. The optimized formulation with highest potential for ophthalmic delivery of diclofenac sodium, good cytotoxicity profile, delicate balance of the mucoadhesivity, and mucus permeation was in the design space of Chitosan/Lutrol F127 micelles.
SN - 2190-3948
UR - https://doi.org/10.1007/s13346-021-01030-4
DO - 10.1007/s13346-021-01030-4
ID - Koummich2022
ER -
Subjects