Facile route to targeted, biodegradable polymeric prodrugs for the delivery of combination therapy for malaria

dc.contributor.authorFortuin, Lisa
dc.contributor.authorLeshabane, Meta Kgaogelo
dc.contributor.authorPfukwa, Rueben
dc.contributor.authorCoertzen, Dina
dc.contributor.authorBirkholtz, Lyn-Marie
dc.contributor.authorKlumperman, Bert
dc.date.accessioned2021-02-17T13:37:30Z
dc.date.issued2020-10
dc.description.abstractA facile synthetic methodology has been developed to prepare multifaceted polymeric prodrugs that are targeted, biodegradable, and nontoxic, and used for the delivery of combination therapy. This is the first instance of the delivery of the WHO recommended antimalarial combination of lumefantrine (LUM, drug 1) and artemether (AM, drug 2) via a polymeric prodrug. To achieve this, reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization of N-vinylpyrrolidone (NVP) was conducted using a hydroxy-functional RAFT agent, and the resulting polymer was used as the macroinitiator in the ring-opening polymerization (ROP) of α-allylvalerolactone (AVL) to synthesize the biodegradable block copolymer of poly(N-vinylpyrrolidone) and poly(α-allylvalerolactone) (PVP-b-PAVL). The ω-end thiol group of PVP was protected using 2,2′-pyridyldisulfide prior to the ROP, and was conveniently used to bioconjugate a peptidic targeting ligand. To attach LUM, the allyl groups of PVP-b-PAVL underwent oxidation to introduce carboxylic acid groups, which were then esterified with ethylene glycol vinyl ether. Finally, LUM was conjugated to the block copolymer via an acid-labile acetal linkage in a “click”-type reaction, and AM was entrapped within the hydrophobic core of the self-assembled aggregates to render biodegradable multidrug-loaded micelles with targeting ability for combination therapy.en_ZA
dc.description.departmentBiochemistryen_ZA
dc.description.departmentGeneticsen_ZA
dc.description.departmentMicrobiology and Plant Pathologyen_ZA
dc.description.embargo2021-10-07
dc.description.librarianhj2021en_ZA
dc.description.sponsorshipThe South African Research Chairs Initiative of the Department of Science and Technology (DST), the National Research Foundation (NRF) of South Africa, SARCHI: Communities of Practice in Malaria Elimination and SARChI Research Chair UID 84627 and UID 84627.en_ZA
dc.description.urihttp://pubs.acs.org/journal/absebaen_ZA
dc.identifier.citationFortuin, L., Leshabane, M., Pfukwa, R. et al. 2020, 'Facile route to targeted, biodegradable polymeric prodrugs for the delivery of combination therapy for malaria', ACS Biomaterials Science and Engineering 2020, 6, 11, 6217–6227.en_ZA
dc.identifier.issn2373-9878 (online)
dc.identifier.other10.1021/acsbiomaterials.0c01234
dc.identifier.urihttp://hdl.handle.net/2263/78737
dc.language.isoenen_ZA
dc.publisherAmerican Chemical Societyen_ZA
dc.rights© 2020 American Chemical Societyen_ZA
dc.subjectDrug deliveryen_ZA
dc.subjectPolymeric prodrugen_ZA
dc.subjectNanomedicineen_ZA
dc.subjectCombination therapyen_ZA
dc.subjectMalariaen_ZA
dc.titleFacile route to targeted, biodegradable polymeric prodrugs for the delivery of combination therapy for malariaen_ZA
dc.typePostprint Articleen_ZA

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