UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Hansen solubility parameters as a predictive tool for the development of oral polymeric nanoparticle delivery systems

Ezekwem, Akunnaya; (2023) Hansen solubility parameters as a predictive tool for the development of oral polymeric nanoparticle delivery systems. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[thumbnail of Akunnaya Ezekwem PhD Thesis.pdf]
Preview
Text
Akunnaya Ezekwem PhD Thesis.pdf - Other

Download (13MB) | Preview

Abstract

Oral drug delivery proves to be the ideal means of drug administration however it is associated with challenges such as drug dissolution and drug permeability, particularly in BCS class IV drugs. These contribute to a reduction in drug bioavailability which accounts for 40% of failures in the developmental stages of oral drug formulations. As a result, drug delivery systems have been designed to alleviate these obstacles and improve oral delivery of various drugs. An example of such drug delivery systems is the use of N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N trimethyl-6-O-glycolchitosan (GCPQ) as nanocarriers. An amphiphilic polymer which has the ability to self-assemble into micelles in solution which are then able to traverse the mucosal layer – a common limitation in oral drug delivery. GCPQ comprises of a range of functional groups which could be chemically modified to achieve required properties. Investigation of various modifications using polymer chemistry allows for a better understanding of the independent effects and relative importance of each individual modification on the process of drug delivery. However, the empirical approach to optimisation of drug delivery systems can be time consuming and resource intensive, potentially also contributing to an increase in time to market. Theoretic predictions have been utilised as a means to evade these challenges. An example of these approaches is the Hansen Solubility Parameters (HSP) predictive tool. HSP was employed using two class IV drugs (curcumin and caspofungin), and their interactions with GCPQ constituents was analysed to guide experimental design. This showed unfavourable predictions despite evidence to support encapsulation capability of GCPQ. Encapsulation experiments carried out with varying degrees of palmitoylation (DP) and quaternisation (DQ) showed data contrary to HSP predictions with EE of curcumin and caspofungin reaching 90% and 96% respectively. A thin film method was used and formulations characterised, with their accelerated stability in aqueous solution studied under two storage conditions for one week. Upon oral administration in vivo, GCPQ-CFG 5mg/kg enhanced bioavailability to a comparable degree as caspofungin acetate, the soluble formulation of caspofungin, with plasma Cmax values of 242±361ng/mL at a Tmax of two hours. Biodistribution analysis showed trace amounts of caspofungin were also found in liver and heart tissues up to 12 hours post dosing at 20 ng/kg and 60ng/kg respectively. An oral CFG formulation has been prepared with the ability to increase oral bioavailability of drug systemically.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Hansen solubility parameters as a predictive tool for the development of oral polymeric nanoparticle delivery systems
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10176111
Downloads since deposit
145Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item