Fabrication of Alginate/Calcium Carbonate Hybrid Microparticles for Synergistic Drug Delivery.

A hybrid drug delivery system coloaded with different drugs for synergistic drug delivery was developed. Alginate/calcium carbonate (CaCO3) hybrid microparticles (MPs) were fabricated via a facile coprecipitation method under mild conditions without using any organic solvent and surfactant. Due to the incorporation of negatively charged alginate chains onto the surface, the obtained hybrid MPs with spherical morphology showed good colloidal stability in an aqueous solution. An antitumor drug (doxorubicin, DOX) and a drug resistance reversal agent (verapamil, VP) were coloaded in the hybrid MPs simultaneously to obtain dual-drug-loaded MPs (DOX/VP/MP). Due to the presence of inorganic CaCO3 (∼54 wt%), the drugs could be loaded in the hybrid MPs with high encapsulation efficiency and the drug release could be effectively sustained. The cell growth inhibition of the drug-loaded MPs was evaluated in HeLa cells. An in vitro study showed DOX/VP/MP exhibited higher cell growth inhibition as compared with DOX monodrug-loaded MPs (DOX/MP). These results suggest the hybrid MPs can potentially be used as a synergistic drug delivery platform for cancer chemotherapy.

In situ formation of thermosensitive PNIPAAm-based hydrogels by Michael-type addition reaction.

To investigate the possibility of in situ thermosensitive hydrogel formation via Michael-type addition reaction, we designed and prepared thiol- and vinyl-modified poly(N-isopropylacrylamide) (PNIPAAm)-based copolymers. When the solutions of these two kinds of PNIPAAm-based copolymers were mixed at physiological temperature (37 degrees C), a physical gelation resulting from the hydrophobic aggregation of PNIPAAm based copolymers and chemical cross-linking between thiol and vinyl functional groups or so-called chemical gelation occurred, resulting in the formation of a three-dimensional hydrogel. Because all the gelations were performed at a high temperature (above LCSTs of the PNIPAAm based copolymers), these in situ formed hydrogels presented heterogeneous network structures, resulting in an improved thermosensitivity in comparison with the conventional one.

Modular Synthesis of Thermosensitive P(NIPAAm-co-HEMA)/ß-CD Based Hydrogels via Click Chemistry.

Two kinds of representative polymers, poly(N-isopropylacrylamide) (PNIPAAm) and ß-cyclodextrin (ß-CD) were selected and modified with azide and alkyne fucntional groups, respectively. When the solutions of these two modified polymers were mixed together, a cross-linking reaction, a type of Huisgen's 1,3-dipolar azide-alkyne cycloaddition, occurred in the presence of Cu(I) catalyst. The strategy described here provides several advantages for the hydrogel formation including mild reaction conditions and controllable gelation rate. The resulted hydrogels were studied in terms of scanning electric microscopy (SEM), equilibrium swelling ratio and swelling/shrinking kinetics. The data obtained demonstrated the hydrogels had a porous structure as well as favorable thermosensitivity.

Study on novel hydrogels based on thermosensitive PNIPAAm with pH sensitive PDMAEMA grafts.

A series of novel hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm) with pendant poly(N-(2-(dimethylamino) ethyl)-methacrylamide) (PDMAEMA) grafts were designed and synthesized. The influence of the pendant PDMAEMA grafts on the properties of the resulted hydrogels was examined in terms of morphology observed by scanning electron microscopy (SEM), thermal property characterized by differential scanning calorimetry (DSC) and shrinking/swelling kinetics upon external temperature changes. In comparison with the conventional PNIPAAm hydrogels, resulting hydrogels presented favorable pH sensitivity as well as improved thermosensitive properties, including enlarged water containing capability at room temperature and faster shrinking/swelling rate upon heating. In addition, fish DNA, used as a model drug, was loaded into the hydrogels, and the controlled release behavior of the drug-loaded hydrogels at different temperatures (22 and 37 degrees C) was further studied.

Synthesis and properties of pH and temperature sensitive P(NIPAAm-co-DMAEMA) hydrogels.

In order to investigate the influence of the continuous alkylamide sequence having pH sensitive unit on the temperature sensitivity of poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogel, a monomer, N-(2-(dimethylamino) ethyl)-methacrylamide (DMAEMA), having an ethylamide group as well as an aliphatic tertiary amino group, was designed and synthesized. Hydrogels based on NIPAAm and DMAEMA were prepared via free radical polymerization. The resulted P(NIPAAm-co-DMAEMA) hydrogels were characterized in terms of maximum swelling ratio, swelling kinetics, temperature response kinetics, and effect of pH. The data obtained show that the novel hydrogels have the strong desire to respond to external temperature and pH stimuli. Importantly, because the P(NIPAAm-co-DMAEMA) hydrogels have the continuous alkylamide sequence containing isopropylamide pendant groups from PNIPAAm and ethylamide pendant groups from PDMAEMA, the incorporation of DMAEMA moiety not only provides the pH sensitivity, but also maintains the thermal properties of P(NIPAAm-co-DMAEMA) hydrogels, even as the molar percentage of DMAEMA moiety reaches 14 mol%.

Fabrication of fast responsive, thermosensitive poly(N-isopropylacrylamide) hydrogels by using diethyl ether as precipitation agent.

An effective strategy was developed and demonstrated to improve the properties of thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel by using diethyl ether as a precipitation agent during the polymerization/crosslinking. Results reveal that the modified PNIPAAm hydrogels have the heterogeneous network structures and decreased LCSTs in a comparison with the normal PNIPAAm hydrogel. The modified PNIPAAm hydrogels also exhibit significantly improved sensitive properties, including fast response and stable, rapid, large magnitude oscillatory shrinking-swelling upon temperature cycles around lower critical solution temperature. In addition, fish DNA, used as a model drug, is loaded into the modified PNIPAAm hydrogels, the controlled release behaviors of the drug loaded hydrogels at different temperatures (22 and 37 degrees C) are further examined.

Fabrication of a novel pH-sensitive glutaraldehyde cross-linked pectin nanogel for drug delivery.

A novel pH-sensitive nanogel based on pectin cross-linked with glutaraldehyde (PT-GA) was designed and synthesized for drug delivery. Transmission electron microscope observation shows that the nano-sized gel particles exhibit a spherical morphology. The optical absorbance study of nanogel suspension reveals its pH sensitivity. Cytotoxicity study shows that the nanogel has no apparent inhibitory effect on cells. The in vitro drug-release behavior of the drug-loaded nanogel particles in three kinds of media, i.e., simulated gastric fluid, simulated intestine fluid and simulated colon fluid, was studied. PT-GA nanogel exhibits a faster release at a high pH, and the release could be further accelerated in the presence of pectinolytic enzyme, indicating that the nanogel may be used for colon-specific drug delivery.

Fabrication of a novel temperature sensitive poly(N-isopropyl-3-butenamide) hydrogel.

To investigate the temperature sensitive mechanism and develop temperature sensitive materials, a novel poly(N-isopropyl-3-butenamide) (PNIPBAm) hydrogel was designed and synthesized. The maximum swelling ratio, temperature dependence of swelling ratio and deswelling/reswelling kinetics of the resulted PNIPBAm hydrogel were characterized. The data obtained exhibited that the temperature sensitivity of the PNIPBAm hydrogel depended on the amount of crosslinker, i.e. the temperature sensitivity decreased with the increasing content of crosslinker. This novel temperature sensitive hydrogel would have the potential applications in bioengineering and biotechnology fields.