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Bansal, Kuldeep Kumar (2015) Novel amphiphilic polymers from renewable feedstock: synthesis, characterisation and applications. PhD thesis, University of Nottingham.

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Abstract

Development of novel biodegradable polymers from renewable resources has attracted attention due to the limitations associated with polymers obtained from petroleum resources. The objective of the work presented in this thesis was to develop various novel biodegradable amphiphilic block copolymers from commercially available sustainable feedstocks for drug delivery applications. Synthesis was performed using a reported method under mild reaction conditions.

Renewable δ-decalactone was chosen as a key monomer to synthesise novel amphiphilic block copolymers via ROP using PEG as initiator. A diblock (i.e. mPEG-b-PDL) and a triblock (i.e. PDL-b-PEG-b-PDL) copolymer of poly(decalactone) (PDL) was synthesised and purified successfully. Additionally, a novel triblock copolymer (i.e. mPEG-b-PDL-b-PPDL) was synthesised using ω-pentadecalactone as monomer and mPEG-b-PDL as initiator via ROP to generate a copolymer with different physical properties. Further, a di-block copolymer of ε-caprolactone (i.e. mPEG-b-PCL) was synthesised for comparative studies with novel block copolymers. Micelles of synthesised block copolymers were fabricated using a reported nanoprecipitation method. Micelles fabricated from these novel block copolymers were of sizes <200nm and possessed low critical micelle concentration (CMC) values.

Curcumin and Amphotericin B were successfully encapsulated in the novel block copolymer micelles via nanoprecipitation method. The results obtained from curcumin loading and release studies suggested that these novel PDL block copolymers could perform in similar fashion when compared with poly(caprolactone) (PCL) block copolymer micelles. However, in subsequent study micelle of mPEG-b-PDL gave high loading content compared to mPEG-b-PCL micelles when amphotericin B was used as a drug. Further, a preliminary in vitro degradation study of mPEG-b-PDL micelles was performed and the results proposed that the ester linkage of PDL chain were susceptible to hydrolytic degradation in physiological condition. Additionally, in vitro cytotoxicity studies performed on HCT-116 human colon cancer cells revealed that the novel mPEG-b-PDL micelles have similar toxicity profiles when compared to the well-established mPEG-b-PCL micelles.

Ligand mediated targeting efficiency of novel diblock copolymer micelles was also studied for potential future applications in cancer therapy. Amphiphilic block copolymers using PEG and PDL were synthesised via click chemistry to generate functionalised block copolymers. Folic acid and rhodamine B were used as targeting ligand and tracker dye respectively. Mixed micelles fabricated from functionalised block copolymers (i.e. FA-PEG-b-PDL, RhB-PEG-b-PDL and mPEG-b-PDL) were tested on folate receptor positive (MCF-7 FR+ve) and folate receptor negative (A549 FR-ve) human cancer cell lines for receptor mediated endocytosis. The acquired confocal images demonstrated the nonspecific uptake of the PEG-b-PDL micelles formulations (targeted and non-targeted) in both cell lines selected in current study.

The results obtained from this thesis study suggested that the synthesised novel PDL block copolymer micelles have potential to act as a novel drug delivery system. However, further studies have been proposed to explore the possible applications of these renewable block copolymers.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Alexander, C. Howdle, S.M. Irvine, D. Mantovani, G.
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculties/Schools:	UK Campuses > Faculty of Science > School of Pharmacy
Item ID:	30858
Depositing User:	Lashkova, Mrs Olga
Date Deposited:	19 Nov 2015 10:53
Last Modified:	15 Oct 2017 00:07
URI:	https://eprints.nottingham.ac.uk/id/eprint/30858

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