Biodegradable Amphiphilic Copolymer Containing Nucleobase: Synthesis, Self-Assembly in Aqueous Solutions, and Potential Use in Controlled Drug Delivery

Abstract

Biodegradable nucleobase-grafted amphiphilic copolymer, the methoxyl poly (ethylene glycol)-b-poly (L-lactide-co-2-methyl-2(3-(2,3-dihydroxylpropylthio) propyloxycarbonyl)-propylene carbonate/1-carboxymethylthymine) (mPEG-b- P(LA-co-MPT)), was synthesized. (1)H NMR titration and FT-IR spectroscopy indicated that the hydrogen-bonding could be formed between mPEG-b-P(LA-co-MPT) and 9-hexadecyladenine (A-C16). The hydrophobic microenvironment of the amphiphilic copolymer can protect the complementary multiple hydrogen bonds between mPEG-b-P(LA-co-MPT) and A-C16 from water effectively. The addition of A-C16 not only lowered the critical aggregation concentration (CAC) of mPEG-b-P(LA-co-MPT)/A-C16 nanoparticles (NPs) in aqueous solution but also induced different morphologies, which can be observed by transmission electron microscopy (TEM). Meanwhile, dynamic light scattering (DLS) and turbidometry was utilized to evaluate the effect of temperature and pH change on the stability of mPEG-b-P(LA-co-MPT)/A-C16 NPs. Cytotoxicity evaluation showed good biocompatibility of the mPEG-b-P(LA-co-MPT)/A-C16 NPs. The in vitro drug release profile showed that with the increase of A-C16 content, the doxorubiucin (DOX) release at pH 7.4 decreased, while the faster release rate was observed with the addition of A-C16 with a pH of 5.0. Importantly, DOX-loaded NPs exerted comparable cytotoxicity against MDA-MB-231 cells. This work provided a new method to stabilize NP structure using hydrogen-bonds and would have the potential to be applied in controlled drug delivery.

TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy

“…The CMC of TPGS-g-PLGA/Pluronic F68 mixed micelles was measured by busing pyrene as a fluorescent probe as described (Basu Ray et al, 2006;Kuang et al, 2012). A series of polymer solutions at concentrations ranging from 5 Â 10 À5 mg/mL to 0.5 mg/mL with pyrene at 6 Â 10 À7 M were prepared.…”

Preparation of sodium cholate-based micelles through non-covalent ıbonding interaction and application as oral delivery systems for paclitaxel

“…A physical micelle is synthesized, where the core and shell are reversibly connected by multiple triple hydrogen-bonds. The micelles can undergo shell disruption upon the encountering of specific chemicals or changing of pH, and aggregation and precipitation can occur during shell disruption due to the sharply decreased CMC (Kuang et al, 2012).…”

Supramolecular synthons and pattern recognition in adenine amides – synthesis, structures and thermal properties

“…The DNA double helix is one of the most sophisticated architectures in supramolecular chemistry (18). The helical structure of DNA is formed and stabilised by highly specific supramolecular interactions, among which hydrogen bonds play an essential role because they provide strong multiple binding between complementary nucleobases (adenine-thymine and guanine-cytosine basepairing) (19).…”