Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.647285
Title: Nano and microcarrier drug delivery systems for the treatment of ocular diseases
Author: Elsaid, N.
ISNI:       0000 0004 5366 1726
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2015
Availability of Full Text:
Access through EThOS:
Full text unavailable from EThOS. Please try the link below.
Access through Institution:
Abstract:
Background and purpose: Biodegradable polymers, such as PLGA, are delivery vehicles used to treat posterior segment eye disease, but suffer from poor drug loading and initial burst release. This thesis describes a ‘system-within-system’, PLGA microparticles incorporating chitosan-based nanoparticles, for ranibizumab delivery, and chitosan-containing micelles for transscleral rapamycin delivery. Methods: Synthesis of chitosan-N-acetyl-L-cysteine (CNAC) and octanoyl-chitosan-poly (ethylene glycol) (OChiPEG) were confirmed using spectroscopy. Chitosan/TPP, chitosan/TPP-HA, CNAC and CNAC/TPP nanoparticles containing ranibizumab were prepared then incorporated in PLGA microparticles and characterised for their size, zeta potential, morphologies, solid-state properties, morphology, protein loading, stability, release, in vivo antiangiogenic activity and effects on cell viability. Rapamycin-loaded micelles comprised of OChiPEG and chitosan-incorporated TPGS, CPEG and TPGS/CPEG were also prepared. Micelles were analysed for their size, zeta potential, morphology, stability, solid-state properties, rapamycin entrapment efficiency and ex vivo scleral retention and permeation. Results: Chitosan-based ranibizumab-loaded nanoparticles measured 17 – 350 nm with a zeta potential of -1.4 to + 12 mV; microparticles measured 3.0 – 6.6 µm (-12 to + 9.7 mV). PLGA microparticles appeared mostly spherical; those prepared with chit/TPP, CNAC and CNAC/TPP had spherical nanoparticles on their surface. Microparticle protein content ranged from 13 – 69%. All preparations showed burst release except for the CNAC containing microparticles, which had the slowest release. Ranibizumab released from PLGA microparticles maintained structural integrity, and activity in cell culture. Chit/TPP-HA nanoparticles containing ranibizumab showed enhanced antiangiogenic activity relative to native ranibizumab. Microparticles showed no effect on cell viability up to a concentration of 12.5 mg/mL. Rapamycin loaded micelles measured 11 – 41 nm, with a zeta potential of -1.2 to + 6.8 mV, entrapment efficiency of 75 - 97% and a scleral retention of 7.5 – 44 µg/g. Conclusion: Micelles showed enhanced scleral retention with potential for topical ocular delivery of poorly soluble drugs. The CNAC-containing preparation has potential for the intraocular delivery of protein-based drugs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.647285  DOI: Not available
Share: