Abstract
Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. In this work, two types of CPT-conjugated polymers were synthesized based on poly(β-L-malic acid) (PMLA) derivatives. Folic acid (FA) was introduced into the polymers as tumor targeting group. The micellization behaviors of these polymers and antitumor activity of different self-assembled micelles were investigated. Results indicate that poly(ethylene glycol)-poly(β-L-malic acid)-campotothecin-I (PEG-PMLA-CPT-I, P1) is a grafted copolymer, and could form star micelles in aqueous solution with a diameter of about 97 nm, also that PEG-PMLA-CPT-II (P2) is an amphiphilic block copolymer, and could form crew cut micelles with a diameter of about 76 nm. Both P1 and P2 micelles could improve the cellular uptake of CPT, especially the FA-modified micelles, while P2 micelles showed higher stability, higher drug loading efficiency, smaller size, and slower drug release rate than that of P1 micelles. These results suggested that the P2 (crew cut) micelles possess better stability than that of the P1 (star) micelles and might be a potential drug delivery system for cancer therapy.
Highlights
As drug carriers, biomacromolecules have attracted significant interest in recent years due to their renewability, low toxicity, biocompatibility, and biodegradability[1,2,3,4]
The synthesis process of Poly(β-L-malic acid) (PMLA) was optimized and the yield of MLABz was increased to 30%[15,28]
PMLABz was synthesized by a ring opening polymerization to control the molecular weight and chain end-groups (-COOH)
Summary
Biomacromolecules have attracted significant interest in recent years due to their renewability, low toxicity, biocompatibility, and biodegradability[1,2,3,4]. The abundant reactive functional groups of biomacromolecules, such as hydroxyl, amino and carboxyl, are readily available for linking various bioactive molecules (drugs, ligands, antibodies, etc.). Polysaccharides[3,4] (chitosan, sodium alginate, cyclodextrin, pectin, etc.) and proteins[2] (gelatin, albumin, fibroin, etc.) are currently the most commonly used in drug delivery. Poly(β-L-malic acid) (PMLA) is a natural aliphatic polyester obtained from the microorganism Physarum polycephalum[5], it could degrade into malic acid firstly and degrades into carbon dioxide and water by tricarboxylic acid cycle in vivo[6,7]. PLOS ONE | DOI:10.1371/journal.pone.0162607 September 20, 2016
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