Butsabarat, Klahan (2024) MICELLES FOR OCULAR DRUG DELIVERY. Doctoral thesis, SETU Waterford.
![[thumbnail of BK_PhDThesis.pdf]](https://repository.wit.ie/style/images/fileicons/text.png) |
Text
BK_PhDThesis.pdf Download (25MB) |
Abstract
This research aimed to design polymeric micelles (PMs) that could induce the controlled release of small therapeutic drugs, curcumin (CUR) and fenofibrate (FEB), from the micellar formulation to treat diseases in the posterior segment of the eye. The initial study evaluated the preparation of a PM system based on Pluronic F127 (PF127), which obtained a critical micelle concentration of approximately 0.21 %(w/v) (DI water) and 0.16 %(w/v) (PBS). Moreover, after CUR loading into the micelles, the study demonstrates that CUR/PF127 micelles prepared by thin-film hydration with a nanometer particle size range (46-78 nm, PDI~0.44-0.61) and negative zeta potential values exhibited a high CUR encapsulation efficiency (EE) of 97% at a 1:140 ratio of drug-to-polymer. The ex vivo permeation study revealed a 2.5-fold higher CUR retention in porcine cornea compared to the free CUR as a control group (8 ng/mg of tissue). Consequently, the study explored the combination system between micelles and cyclodextrins (CDs) for ocular drug delivery of FEB. The Soluplus®/PF127/CD poly(pseudo)rotaxanes (PPRs), a type of molecular assembly in which polymer chains are threaded through the cavity of CDs with only non-covalent bonds, enhanced the water solubility of FEB (0.00034 mg/mL) up to 0.31 mg/mL, demonstrating the potential for increased drug bioavailability. In addition, an ex vivo permeation study demonstrated that FEB-loaded PPRs efficiently permeated through the porcine sclera, highlighting their potential to enhance drug absorption and permeation in ocular tissues. A mathematical model was thereafter applied to explain the ex vivo permeation study of FEB-loaded micelles and PPRs, predicting drug delivery across scleral tissue. The calculation showed no significance in diffusivity values across the different FEB PPRs (1-15x10-3 cm2/h), supporting PPR formulations to help FEB transportation across the porcine sclera. The study also investigated the use of PF127 micelles and chitosan as positively charged micelles for FEB drug loading, resulting in bimodal particle size distributions (17-52 nm and 169-661 nm, PDIs~0.6-0.8) and low %EE (6-13% EE), indicating another potential nanocarriers for drug delivery.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | micelles, Pluronic F127, Pluronic F127/CH, curcumin micelles, cyclodextrins, fenofibrate micelles, poly(pseudo)rotaxanes |
| Departments or Groups: | Pharmaceutical and Molecular Biotechnology Research Centre |
| Divisions: | School of Science > Department of Chemical and Life Sciences |
| Depositing User: | Derek Langford |
| Date Deposited: | 15 Oct 2024 14:30 |
| Last Modified: | 15 Oct 2024 14:30 |
| URI: | https://repository.wit.ie/id/eprint/7839 |
Actions (login required)
 |
View Item |
