Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.772035
Title: Development and characterisation of nanocarriers system of hydrophobic drugs for pulmonary delivery
Author: Nimmano, Nattika
ISNI:       0000 0004 7660 875X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Abstract:
Background: The bioavailability of BCS class II drugs used in non-small cell lung cancer (NSCLC) treatment is limited by low water solubility. Also, current therapies for NSCLC cause systemic side effects and sub-therapeutic levels of drugs at the target sites. Colloidal systems administered by the pulmonary route may overcome these problems. Method: A genistein-mPEG conjugate was synthesised and characterised for delivering erlotinib or curcumin in micelles. Liposomes co-loaded with genistein and erlotinib were developed as an alternative formulation approach and studies using DSC and HPLC analysis. The aerosol properties of micelles and liposomes were measured using the Next Generation Impactor (NGI). The Fast Screening Impactor (FSI) was investigated as an alternative to the NGI for aerosol characterisation of nebulised liposomes. Three parameters (nebuliser types, impactor operating conditions and liposome size reduction methods) were studied using the FSI. Results: Successful conjugation was confirmed by FT-IR, NMR and MS. Curcumin loading into conjugate micelles had mean size < 200nm, with ≈ 50% encapsulation efficiency (EE). However, the genistein conjugate was not appropriate for erlotinib delivery, having low EE (<3%). For liposomes, the mean size was ≈130 nm, with 10% EE (erlotinib) and 100% EE (genistein). DSC results showed incorporation of both drugs into the bilayer, giving a broadening of the main phase transition of DPPC with a decreased main phase temperature. The air-jet nebuliser was superior to the vibrating-mesh device in terms of significantly higher fine particle dose (FPD) and fine particle fraction (FPF). The FSI (5± 3 ºC), with modification operated at 15 L/min, was found to be simple to use and labour-saving for simple aerosol characterisation, giving comparable results to the NGI for FPD and FPF. Extruded liposomes showed greater size stability than sonicated vesicles during preparation and nebulisation. Conclusions: Optimised micelles and liposomes with desired mean size and drug entrapments have the potential for nebuliser delivery of genistein, erlotinib and curcumin, and may be suitable for delivering other hydrophobic drugs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.772035  DOI: Not available
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