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Currently, repeated routine subcutaneous injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, patients' poor compliance for injections often fails to achieve the stable concentration of blood glucose. As a protein drug, the oral bioavailability of insulin is low due to many physiological reasons. Several carriers, such as macromolecules and liposomes have been used to deliver drugs in vivo. In this review article, the gastrointestinal barriers of oral insulin administration are described. Strategies for increasing the bioavailability of oral insulin, such absorption enhancers, enzyme inhibitors, enteric coatings are also introduced. The potential absorption mechanisms of insulin-loaded nanoparticles across the intestinal epithelium, including intestinal lymphatic route, transcellular route and paracellular route are discussed in this review. Natural polymers, such as chitosan and its derivates, alginate derivatives, γ-PGA-based materials and starch-based nanoparticles have been exploited for oral insulin delivery; synthetic polymers, such as PLGA, PLA, PCL and PEA have also been developed for oral administration of insulin. This review focuses on recent advances in using biodegradable natural and synthetic polymers for oral insulin delivery along with their future prospects.

Poly(lactic acid)-b-Pluronic-b-poly(lactic acid) (PLA-P85-PLA) vesicles were developed as novel carrier for oral insulin delivery. PLA-P85-PLA block copolymer was synthesized by ring opening polymerization of the monomer l-lactide using Pluronic copolymer P85 as the initiator. Insulin-loaded PLA-P85-PLA vesicles were prepared by dialysis method and the mean diameter of insulin-loaded PLA-P85-PLA vesicles was determined to be 178 nm. The cytotoxicity studies using human ovarian cancer cells OVCAR-3 indicate that PLA-P85-PLA block copolymer has good biocompatibility. Both in vitro and in vivo release behavior of insulin loaded in PLA-P85-PLA vesicles were studied. It was observed that insulin was released out gradually from PLA-P85-PLA vesicles and almost all insulin was released out 7.5h later. More importantly, for the oral administration of insulin-loaded PLA-P85-PLA vesicles at insulin doses of 200 IU/kg, the minimum blood glucose concentration was observed in the diabetic mice test after 2.5h, which was 15% of initial glucose level. Furthermore, the blood glucose concentration increased slowly to 31.8% of initial blood glucose concentration after 10.5h and was maintained at this level for at least an additional 14h (32.5% of initial blood glucose concentration at 24.5h). These results proved that PLA-P85-PLA vesicles could be promising polymeric carriers for oral insulin delivery application due to their sustained and enhanced hypoglycemic effect., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In order to prepare targeted drug carriers, previously a biotin group has been attached by our group to the end of Pluronic F87/poly(lactic acid) and Pluronic P85/poly(lactic acid) block co-polymers to obtain B-F87-PLA and B-P85-PLA, respectively. In this paper, the active targeting properties of B-F87-PLA and B-P85-PLA nanoparticles in vitro were investigated through a three-step biotin-avidin interaction by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM). Two kinds of human ovarian cancer cells (OVCAR-3 and SKOV-3) and paclitaxel were chosen for the cytotoxicity tests. CA-125 antigen is over-expressed on OVCAR-3 cells but not on SKOV-3 cells. The loading and release behavior of paclitaxel loaded in B-Pluronic-PLA nanoparticles were also studied. Paclitaxel loaded in both B-F87-PLA and B-P85-PLA nanoparticles shows an initial rapid release followed by a slow release period. Compared with SKOV-3 cells, the cytotoxicity results implied that paclitaxel-loaded B-Pluronic-PLA nanoparticles were delivered more effectively to OVCAR-3 cells due to the specific interaction between the biotin groups on the surface of B-Pluronic-PLA nanoparticles and the avidin/biotinylated MAb X306/CA-125 antigen complexes on the surface of OVCAR-3 cells. The active targeting properties of B-F87-PLA nanoparticles were further confirmed by FM.

The article focuses on the comparison of poly(L-lactic acids) (PLLA)-poly(ethylene oxide) (PEO)-PLLA triblock copolymers and PLLA-PEO-PPO-PEO-PLLA pentablock copolymers' self-assembling behaviors. The authors used the Dynamic Light Scattering and Transmission Electron Microscopic techniques in comparing the self-assembling behaviors of the two copolymers. They conclude that within the PLLA-PEO-PPO-PEO-PLLA pentablock copolymers, the PPO segment plays a significant part in the vesicles formation.

Abstract: Adsorption behaviors of maleic anhydride sodium salt copolymer on the zinc oxide surface were studied in aqueous suspensions. FTIR spectroscopic data provided evidence in support of hydrogen bonding and chemical interaction between the copolymer and ZnO. Adsorption density decreased with an increase of pH. Thickness of adsorption layer increased with the increase of pH and copolymer concentration. A detailed study of ionic strength effect showed that an increasing monovalent salt concentration resulted in the increase of adsorption density, while the density decreased with the further increasing salt concentration. The adsorption density in the presence of CaCl2 solution was greater than that in the NaCl solution of the same concentration. The shift of pHiep towards lower pH value was observed in the presence of MA–Na copolymer. [Copyright &y& Elsevier]

Abstract: The colloidal stabilization of nano-sized zinc oxide suspensions with maleic anhydride sodium salt copolymer is examined to understand the primary mechanism of dispersion. FTIR spectroscopic data provided evidence in support of hydrogen bonding and chemical interaction in the case of the MA-Na copolymer/ZnO system. The suspension stability was characterized by sedimentation tests and TEM method. The copolymer was found to stabilize the suspension of ZnO nanoparticles through electrosteric repulsion. Influences of factors such as pH and the copolymer concentration on the colloidal stability of aqueous suspension were investigated. The copolymer at high pH of the solution provided more effective degree of sustained particle dispersion. The adsorbed MA-Na copolymer provided a good stabilization under the saturated adsorption amount, while the excess copolymer flocculated the dispersed system. [Copyright &y& Elsevier]