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Liquid Degradable Poly(trimethylene-carbonate-co-5-hydroxy-trimethylene carbonate): An Injectable Drug Delivery Vehicle for Acid-Sensitive Drugs
journal contribution
posted on 2020-02-24, 15:57 authored by Sara Mohajeri, Fei Chen, Mitchell de Prinse, Ta Phung, Jonah Burke-Kleinman, Donald H. Maurice, Brian G. AmsdenLiquid,
injectable hydrophobic polymers have advantages as degradable
drug delivery vehicles; however, polymers examined for this purpose
to date form acidic degradation products that may damage acid-sensitive
drugs. Herein, we report on a new viscous liquid vehicle, poly(trimethylene
carbonate-co-5-hydroxy-trimethylene carbonate), which
degrades through intramolecular cyclization producing glycerol, carbon
dioxide, and water-soluble trimethylene carbonate. Copolymer degradation
durations from weeks to months were achieved with the 5-hydroxy-trimethylene
carbonate (HTMC) content of the oligomer having the greatest impact
on the degradation rate, with oligomers possessing a higher HTMC content
degrading fastest. The degradation products were non-cytotoxic towards
3T3 fibroblasts and RAW 264.7 macrophages. These copolymers can be
injected manually through standard gauge needles and, importantly,
during in vitro degradation, the microenvironmental pH within the
oligomers remained near neutral. Complete and sustained release of
the acid-sensitive protein vascular endothelial growth factor was
achieved, with the protein remaining highly bioactive throughout the
release period. These copolymers represent a promising formulation
for local and sustained release of acid sensitive drugs.
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date form acidic degradation productsgauge needles3 T 3 fibroblastsacid-sensitive proteincarbon dioxidecopolymersCopolymer degradation durationsdegradation rateInjectable Drug Delivery VehicleHTMC contentmicroenvironmental pHtrimethylene carbonatedegradation productsgrowth factordegradable drug delivery vehicles5- hydroxy-trimethylene carbonateRAW 264.7 macrophagesAcid-Sensitive Drugs Liquidrelease periodoligomerintramolecular cyclizationacid-sensitive drugs-5-
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