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Targeted drug delivery systems have attracted increasing attention due to their ability for delivering anticancer drugs selectively to tumor cells. Folic acid (FA)-conjugated targeted block copolymers, FA-Pluronic-polycaprolactone (FA-Pluronic-PCL) are synthesized in this study. The anticancer drug paclitaxel (PTX) is loaded in FA-Pluronic-PCL nanoparticles by nanoprecipitation method. The in vitro release of PTX from FA-Pluronic-PCL nanoparticles shows slow and sustained release behaviors. The effect of FA ligand density of FA-Pluronic-PCL nanoparticles on their targeting properties is examined by both cytotoxicity and fluorescence methods. It is shown that FA-Pluronic-PCL nanoparticles indicated better targeting ability than non-targeted PCL-Pluronic-PCL nanoparticles. Furthermore, FA-F127-PCL nanoparticle with 10% FA molar content has more effective antitumor activity and higher cellular uptake than those with 50% and 91% FA molar content. These results prove that FA-F127-PCL nanoparticle with 10% FA molar content can be a better candidate as the drug carrier in targeted drug delivery systems., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Novel Folated Pluronic F127/poly (lactic-co-glycolic) (FA-F127-PLGA) and PLGA-F127-PLGA block copolymer were synthesized and nanoparticles self-assembled from these two copolymers were prepared by dialysis method. Paclitaxel (PTX) was successfully encapsulated in these two nanoparticles. According to in vitro release studies of PTX-loaded nanoparticles, after an initial burst release during the first 11h, the entrapped PTX released slowly in the following 82h. The cytotoxicity studies demonstrated that the in vitro antitumor effect of PTX could be improved by encapsulating PTX into PLGA-F127-PLGA nanoparticles. Moreover, folate-targeted FA-F127-PLGA nanoparticles were more effective than PLGA-F127-PLGA when delivering PTX in folate receptor overexpressing OVCAR-3 cells, which mainly due to the FA-receptor-meditated endocytosis. As the treatment time became longer, the targeting effects were more obvious. The targeting effect of FA-F127-PLGA nanoparticles was also investigated in vitro by measuring the cellular uptake of the nanoparticles. The results showed that FA-F127-PLGA nanoparticles were more easily to be uptaken by OVCAR-3 cells in comparison with PLGA-F127-PLGA nanoparticles. In vivo pharmacokinetic studies indicated that FA-F127-PLGA nanoparticles prolong the circulation time of PTX in plasma, and delay the blood clearance of PTX. These results indicated that Folated FA-F127-PLGA could be a potential carrier in long-term PTX delivery., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

Biotinylated Pluronic F127/poly(lactic acid) block copolymers (B-F127-PLA) were successfully synthesized previously by our group. In the present study, the release behaviors of paclitaxel-loaded B-F127-PLA nanoparticles and their targeting properties to human ovarian carcinoma cells were investigated. Paclitaxel (pac) loaded in B-F127-PLA nanoparticles shows an initial burst release in the first 6h and followed by a slow release. The in vitro targeting behaviors of B-F127-PLA nanoparticles against human ovarian cancer cells (OVCAR-3, SKOV-3) were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM) technique. Targeting was based on a three-step biotin-avidin targeting approach using biotinylated anti-CA125 antibody specific for the CA-125 antigen that is highly expressed on OVCAR-3 cells but not expressed on SKOV-3 cells. MTT results show that the anticancer effect of paclitaxel in B-F127-PLA nanoparticles over OVCAR-3 cells was stronger than that over SKOV-3 cells, indicating that B-F127-PLA nanoparticles were delivered more effectively to OVCAR-3 cells than to SKOV-3 cells. The targeting behaviors of B-F127-PLA nanoparticles were further confirmed by FM technique. The intracellular distribution of B-F127-PLA nanoparticles was also studied using a triple-labeling method. It was observed that B-F127-PLA nanoparticles are mainly localized within the cytoplasm of OVCAR-3 cells. The in vivo antitumor efficacy of pac-loaded B-F127-PLA nanoparticles by three-step method as measured by change in tumor volume of OVCAR-3 implanted in Balb/C nude mice was greater than that by one-step method., (Copyright © 2012 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 morphologies of poly(lactic acid)-b-Pluronic-b-poly(lactic acid) (PLA-F127-PLA) aggregates in aqueous solutions were reported previously to be vesicular nano-particles by our group. In the present study, we seek to investigate the feasibility of using PLA-F127-PLA vesicles as oral delivery carrier for insulin. Both in vitro and in vivo release behavior of insulin loaded in PLA-F127-PLA vesicles were studied. A biphasic release behavior was observed for the in vitro release of insulin from PLAF127-29 vesicles. More importantly, it was found in the diabetic mice tests that the blood glucose concentration of oral insulin-loaded PLAF127-29 vesicles decreased from 18.5 to 5.3 mmol/L within 4.5 h and the minimum blood glucose concentration (about 4.5 mmol/L) was achieved after about 5 h. Furthermore, the blood glucose concentration was maintained at this level for at least an additional 18.5 h. These results proved that PLA-F127-PLA vesicles could be promising polymeric carriers for oral insulin delivery application due to their prolonged hypoglycemic effect.

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. [ABSTRACT FROM AUTHOR]

The article presents a study which synthesized Biotinylated Pluronic/poly(lactic acid) (PLA) block copolymers to obtain polymeric nanoparticles with biotin groups on the surface. Fluorescence measurement, dynamic light scattering (DLS) and transmission electron microscopic (TEM) techniques were used to examine the self-assembling behaviors of Biotin-Pluronic-PLA block copolymers in aqueous solutions. It was found that Biotin-Pluronic-PLA block copolymers have good biocompatibility.

Abstract: Adsorption of cationic polyelectrolyte, a homopolymer of maleimide propyl trimethylammonium chloride (MPTMAC), on silica nanoparticles from aqueous solution was studied. The adsorbed amount of MPTMAC and the adsorption layer thickness from solutions of different pH, polyelectrolyte concentration, salt type, and salt concentration were measured. The adsorbed amount exhibited a maximum as a function of the electrolyte concentration. The onset of the decline in the adsorbed amount depended on the type of counterions. The thickness of the adsorption layer increased gradually with increased of electrolyte concentration and leveled off at high electrolyte concentration. The enhanced adsorption in the presence of Na2SO4 can be explained by the bivalent SO2-4 causing a better shielding effect. With increasing pH the adsorbed amount of MPTMAC increased, whereas the thickness of an adsorbed layer of MPTMAC decreased. At low polyelectrolyte concentrations unstable silica suspensions were observed from a stability test. At high polyelectrolyte concentrations the higher particle coverage caused electrosteric stabilization of the dispersion. However, further increase in MPTMAC concentration after saturated adsorption would flocculate the dispersed system. At low pH, MPTMAC tending to create a loops or tails conformation stabilized the suspension. [Copyright &y& Elsevier]