Abstract
Purpose :
Eye drops suffer from low efficiency due to high turnover rate of the aqueous tear film layer, drug dilution, and drainage via the nasolacrimal ducts. These clearance mechanisms result in less than 5% of the applied dose remaining on the target site 5 minutes after administration.
Nanotechnologies such as nanoparticles, emulsions, dendrimers, and micelles can be incorporated into eye drop formulations to increase the residence time of the drug and improve bioavailability. A mucoadhesive micelle incorporating phenylboronic acid has been shown to form a complex with diols in the mucin layer of the tear film, exploiting the relatively slow turnover of the mucin, reducing rapid drug clearance to decrease dosage frequency. However, the pH sensitivity of this micelle polymer limits drug compatibility. In this work, a modified micelle formulation was prepared to reduce the pH sensitivity of the micelles.
Methods :
A mucoadhesive polymer, poly(L-lactide)-b-poly(methacrylic acid-co-3-acrylamidophenylboronic acid), was synthesized. The structure and molecular weight of the polymer was determined using 1HNMR. Polymeric micelles were formed and characterized with and without dexamethasone (DEX), loaded as a model drug, using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and TEM. The loading and release of DEX was quantified using HPLC.
Results :
NMR showed molecular weights similar to the previously synthesized polymer formulations. Micelle formation was observed in both PBS and water with a neutral pH. There was no visible change in solution opacity following pH manipulation. Nanoparticles were observed to be <100nm via DLS and NTA. TEM of dry state micelles showed spherical particles with limited aggregation. HPLC analysis showed an entrapment efficiency of 23.1 ± 0.8 % and the preliminary release profile of DEX demonstrates there may be slower release in initial stages (<5hrs) compared to the control.
Conclusions :
Expanding the compatibility of this micelle formulation with other drugs may allow for the treatment of more ocular disorders, as well as increasing the breadth of applications beyond the eye to other mucosal membranes, such as nasal and intravaginal treatments.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.