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Liquid 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 copolymer, poly(trimethylene carbonate-co-5-hydroxy-trimethylene carbonate) that degrades through intramolecular cyclization in mild alkaline environments, producing glycerol, carbon dioxide, and water-soluble trimethylene carbonate. Copolymer degradation durations from weeks to months were obtained with 5-hydroxy-trimethylene carbonate (HTMC) content of the copolymer having the greatest impact on degradation rate, with copolymers possessing higher HTMC content degrading fastest. The degradation products of the copolymers 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 copolymer 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 approach for local and sustained release of acid sensitive drugs.
This article was published in the following journal.
Name: Molecular pharmaceutics
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A field of chemistry which pertains to chemical compounds or ions that do not contain the element carbon (with the exception of carbon dioxide and compounds containing a carbonate radical, e.g., calcium carbonate).
Protein-mineral complexes that comprise substrates needed for the normal calcium-carbonate-phosphate homeostasis. Nanobacteria was the prior name for the particles which were originally thought to be microorganisms.
Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.
A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of BIOGENIC MONOAMINES in the CENTRAL NERVOUS SYSTEM, and affects multiple neurotransmission systems.
A group of iron-binding proteins that tightly bind two ferrate ions along with two carbonate ions. They are found in the bodily fluids of vertebrates where they act as transport and storage molecules for iron.
<!--LGfEGNT2Lhm-->Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. <!--LGfEGNT2Lhm-->Drug delivery technologies are <!--LGfEGNT2Lhm-->patent pr...
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