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Information-Based Design of Polymeric Drug Formulation Additives

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journal contribution
posted on 23.11.2020, 21:04 by Sandra Arias, Eva Maron, Hans G. Börner
Tailor-made copolymers are designed based on a peptide-poly­(ethylene glycol) (QFFLFFQ-PEG) conjugate as a blueprint, to solubilize the photosensitizer meta-tetra­(hydroxyphenyl)­chlorin (m-THPC). The relevant functionalities of the parent peptide-PEG are mimicked by employing monomer pairs that copolymerize in a strictly alternating manner. While styrene (S) or 4-vinylbenzyl-phthalimide (VBP) provide aromatic moieties like Phe, the aliphatic isobutyl side chain of Leu4 is mimicked by maleic anhydride (MA) that reacts after polymerization with isobutylamine to give the isobutylamide-carboxyl functional unit (iBuMA). A set of copolymer-PEG solubilizers is synthesized by controlled radical polymerization, systematically altering the length of the functional segment (DPn = 2, 4, 6) and the side chain functionalization (iBuMA, iPrMA, MeMA). The m-THPC hosting and release properties of P­[S-alt-iBuMA]6-PEG reached higher payload capacities and more favored release rates than the parent peptide-PEG conjugate. Interestingly, P­[S-alt-RMA]n-PEG mimics the sensitivity of the peptide-PEG solubilizer well, where the exchange of Leu4 residue by Val and Ala significantly reduces the drug loading by 92%. A similar trend is found with P­[S-alt-RMA]n-PEG as the exchange of iBu → iPr → Me reduces the payload capacity up to 78%.