Guolin Li

Polymeric micelles with water-insoluble drug as hydrophobic moiety for drug delivery.

The hydrophobic block of polymeric micelles formed by amphiphilic copolymers has no direct therapeutical effect, and the metabolites of these hydrophobic segments might lead to some unexpected side effects. Here the hydrophobic core of polymeric micelles is replaced by highly water-insoluble drugs themselves, forming a new micellar drug delivery system. By grafting hydrophobic drugs of paclitaxel (PTX) onto the surface of hydrophilic hyperbranched poly(ether-ester) (HPEE), we constructed an amphiphilic copolymer (HPEE-PTX). HPEE-PTX could self-assemble into micellar nanoparticles in aqueous solution with tunable drug contents from 4.1 to 10.7%. Moreover, the hydrolysis of HPEE-PTX in serum resulted in the cumulative release of PTX. In vivo evaluation indicated that the dosage toleration of PTX in mice had been improved greatly and HPEE-PTX micellar nanoparticles could be used as an efficient prodrug with satisfactory therapeutical effect. We believe that most of the lipophilic drugs could improve their characters through this strategy.

Biodegradable Hyperbranched Polyglycerol with Ester Linkages for Drug Delivery

Biodegradable hyperbranched polyglycerols (dHPGs) were synthesized through oxyanionic initiating hybrid polymerization of glycerol and glycidyl methacrylate. Due to the introduction of ester linkages into the hyperbranched polyglycerol backbone, dHPGs showed good biodegradability and low cytotoxicity. Benefiting from the existence of terminal hydroxyls and methacryloyl groups, both the anticancer drug methotrexate (MTX) and fluorescent probe Rhodamine-123 could be conjugated onto the surface of dHPGs easily. The resultant MTX-conjugated polymers (dHPG-MTXs) exhibited an amphiphilic character, resulting in the formation of micelles in an aqueous solution. The release of MTX from micelles was significantly faster at mildly acidic pH of 5.0 compared to physiological pH of 7.4. dHPG-MTX micelles could be efficiently internalized by cancer cells. MTT assay against cancer cells showed dHPG-MTXs micelles had high anticancer efficacy. On the basis of their good biodegradability and low cytotoxicity, dHPGs provide an opportunity to design excellent drug delivery systems.

Self-assembled encapsulation systems with pH tunable release property based on reversible covalent bond

Dynamic diblock polymer PS-r-PEG formed via reversible acylhydrazone connection can be used to construct a pH-responsive self-assembled encapsulation system with high stability and sustained-release property, which shows potential in drug delivery.

Synthesis, Characterization, and in Vitro Evaluation of Long-Chain Hyperbranched Poly(ethylene glycol) as Drug Carrier

A series of novel long-chain hyperbranched poly(ethylene glycol)s (LHPEGs) with biodegradable connections were designed and synthesized in one pot through proton-transfer polymerization using PEG and commercial glycidyl methacrylate as monomers and potassium hydride as catalyst. The LHPEGs were hydrolyzed at neutral pH resulting in the decrease of molecular weights. In vitro evaluation demonstrated that LHPEGs were biocompatible and displayed negligible hemolytic activity. The efficient cellular uptake of LHPEGs was confirmed by flow cytometry and confocal laser scanning microscopy. Moreover, conjugation of a model hydrophobic anticancer drug methotrexate to LHPEGs inhibited the proliferation of a human cervical carcinoma Hela cell line. MTT assay indicated that the conjugated methotrexate dose required for 50% cellular growth inhibition against Hela cells was 20 μg/mL. By combining the advantages of long-chain hyperbranched structure and PEG, LHPEG provides a promising drug carrier for therapeutic fields.

Hybrid Polymerization of Vinyl and Hetero-Ring Groups of Glycidyl Methacrylate Resulting in Thermoresponsive Hyperbranched Polymers Displaying a Wide Range of Lower Critical Solution Temperatures

Hybrid polymerization of glycidyl methacrylate (GMA) with potassium hydride (KH) and various oligo(ethylene glycol)s as the initiating system, in which both vinyl polymerization and ring-opening polymerization occur simultaneously, generates hyperbranched poly(ether-ester)s. The reaction process has been followed by an in situ nuclear magnetic resonance technique. The experimental results indicate that both the vinyl and epoxy groups of GMA undergo polymerization, with the reactivity of the latter being much higher than that of the former. Interestingly, the resulting hyperbranched polymers exhibit a sharp phase transition in water at the lower critical solution temperature (LCST). Significantly, the LCST values can be accurately controlled from 0 to 100 degrees C by changing the hydrophilic/hydrophobic balance of GMA and various oligo(ethylene glycol)s or by modification of the precursor polymer through acetylation. This novel stimuli-responsive hyperbranched polymer is a promising candidate for a new generation of commercially viable thermoresponsive polymers following on from the widely used poly(N-isopropylacrylamide) (PNIPAM).

Doubly Hydrophilic Multiarm Hyperbranched Polymers with Acylhydrazone Linkages as Acid-Sensitive Drug Carriers

A novel type of drug carrier capable of controlled drug release is proposed. It consists of an acid-sensitive doubly hydrophilic multiarm hyperbranched copolymer with a hyperbranched polyamidoamine core and many linear poly(ethylene glycol) arms. Using pH-sensitive acylhydrazone linkages, the polymer forms unimolecular micelles that can encapsulate hydrophobic drugs. Due to their amphiphilicity, the drug-loaded unimolecular micelles can self-assemble into multimolecular micelles that show acid-triggered intracellular delivery of the hydrophobic drugs.