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

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dc.contributor.authorFortuin, Lisaen_ZA
dc.contributor.authorLeshabane, Metaen_ZA
dc.contributor.authorPfukwa, Ruebenen_ZA
dc.contributor.authorCoertzen, Dinaen_ZA
dc.contributor.authorBirkholtz, Lyn-Marieen_ZA
dc.contributor.authorKlumperman, Berten_ZA
dc.date.accessioned2022-05-23T07:37:27Zen_ZA
dc.date.available2022-05-23T07:37:27Zen_ZA
dc.date.issued2020-06en_ZA
dc.descriptionCITATION: Fortuin, L. et al. 2020. Facile route to targeted, biodegradable polymeric prodrugs for the delivery of combination therapy for Malaria. ACS Biomaterials Science & Engineering, 6(11): 6217-6227 doi:10.1021/acsbiomaterials.0c01234en_ZA
dc.descriptionThe original publication is available at https://pubs.acs.org/journal/absebaen_ZA
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.urihttps://pubs.acs.org/doi/10.1021/acsbiomaterials.0c01234en_ZA
dc.description.versionPublisher’s versionen_ZA
dc.format.extent11 pagesen_ZA
dc.identifier.citationFortuin, L. et al. 2020. Facile route to targeted, biodegradable polymeric prodrugs for the delivery of combination therapy for Malaria. ACS Biomaterials Science & Engineering, 6(11): 6217-6227 doi:10.1021/acsbiomaterials.0c01234en_ZA
dc.identifier.issn2373-9878 (online)en_ZA
dc.identifier.otherdoi:10.1021/acsbiomaterials.0c01234en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125226en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherAmerican Chemical Societyen_ZA
dc.rights.holderAmerican Chemical Societyen_ZA
dc.subjectConjugated polymersen_ZA
dc.subjectPolymeric drug delivery systemsen_ZA
dc.subjectNanomedicineen_ZA
dc.subjectCombined modality therapyen_ZA
dc.subjectMalaria -- Preventionen_ZA
dc.titleFacile route to targeted, biodegradable polymeric prodrugs for the delivery of combination therapy for Malariaen_ZA
dc.typeArticleen_ZA
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