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Preparation of biopolymer-drug formulations for cancer drug delivery
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Mannans are highly water-soluble mannose heteropolymers produced by a number of organisms, including yeasts. Polyhydroxyalkanoates (PHAs) are aliphatic polyesters produced by numerous bacteria as a carbon and energy source, with interesting thermal and mechanical properties.
The main objective of this thesis was to prepare different polymeric structures base on mannans and PHAs for use in the pharmaceutical and biomedical areas. Mannans were produced by Komagataella pastoris using glycerol as carbon source, extracted with a heat-alkali treatment and purified using dialysis. PHAs were produced by mixed cultures using fermented fruit pulp waste, extracted using chloroform or hypochlorite and purified in ethanol.
A successful deproteinization and an unsuccessful phosphorylation procedure was performed in mannans. The results show a decrease in protein content of 69.49 ± 0.44 % and a decrease in phosphate content of 60.45 ± 1.23 %, respectively.
Mannans were tested in normal fibroblasts, HCT116 and A2780 cell lines for their cytotoxicity, by MTS assay, and no cytotoxicity was discovered. They were then used to prepare gel structures, and gelled using di- and tri-valent cations of iron and copper at low temperature (4 ⁰C) and alkaline pH. Gel particles were obtained in the above conditions and tested for their stability in water. Particles made using tri-valent iron were found the most stable.
Mannans were also used to produce films. Films were obtained from i) mannans in water dried at 30 ⁰C or freeze dried, ii) from the previously produced films (30 ⁰C) and then coated with iron, at neutral pH or followed by immersion in an alkaline solution and, iii) from gel beads dried at 30 ⁰C or freeze dried. Films were tested for cell adhesion in vitro using normal fibroblasts, but no positive results were found.
PHAs with different HV ratios were used to produce films, pure and blended with mannans, using chloroform as solvent by a solvent casting method. The produced films were tested for cell adhesion in vitro, using fibroblasts and MCF7-GFP. Pure PHA films were deemed good matrices for this application with cells adherent to their surface, whereas blend matrices failed in this regard. Some pure PHA matrices were then tested for their cytotoxicity using MCF7-GFP, and with the exception of co-polymer PHBHV with HV content of 18 % (extracted with hypochlorite), they were found to be non-cytotoxic, rendering them useful for biomedical applications such as wound dressing or drug delivery.
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Palavras-chave
Mannans Polyhydroxyalkanoates Mannans gel beads Polymeric Films Cytotoxicity assays Cell adherence assays