Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11-15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W1/O/W2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil-water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

Preparation and evaluation of amphipathic lipopeptide-loaded PLGA microspheres as sustained-release system for AIDS prevention.

At present, AIDS drugs are typical inhibitors that cannot achieve permanent effects. Therefore, the research of blocking HIV infection is essential. Especially for people in the high-risk environment, long-term prevention is important, because HIV can easily infect cells once the drug is interrupted. However, there is still no long-acting AIDS prevention drug approved. Hence, the purpose of this study is to prepare a fusion inhibitor loaded poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release system for long-term AIDS prevention. As the HIV membrane fusion inhibitor (LP-98) used in this research is amphiphilic lipopeptide, W1/O/W2 double-emulsion method was chosen, and premix membrane emulsification technique was used for controlling the uniformity of particle size. Several process parameters that can impact drug loading efficiency were summarized: the concentration of LP-98 and PLGA, and the preparation condition of primary emulsion. Finally, the microspheres with high loading efficiency (>8%) and encapsulation efficiency (>90%) were successfully prepared under optimum conditions. Pharmacokinetic studies showed that LP-98-loaded microspheres were capable to continuously release for 24 days in rats. This research can promote the application of sustained-release microspheres in AIDS prevention, and the embedding technique used in this study can also provide references for the loading of other amphipathic drugs.

A phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing.

Phagocytosis is one of the earliest cellular functions, developing approximately 2 billion years ago. Although FcR-based phagocytic signaling is well-studied, how it originated from ancient phagocytosis is unknown. Lipid redistribution upregulates a phagocytic program recapitulating FcR-based phagocytosis with complete dependence on Src family kinases, Syk, and phosphoinositide 3-kinases (PI3K). Here we show that in phagocytes, an atypical ITAM sequence in the ancient membrane anchor protein Moesin transduces signal without receptor activation. Plasma membrane deformation created by solid structure binding generates phosphatidylinositol 4,5-bisphosphate (PIP2) accumulation at the contact site, which binds the Moesin FERM domain and relocalizes Syk to the membrane via the ITAM motif. Phylogenic analysis traces this signaling using PI3K and Syk to 0.8 billion years ago, earlier than immune receptor signaling. The proposed general model of solid structure phagocytosis implies a preexisting lipid redistribution-based activation platform collecting intracellular signaling components for the emergence of immune receptors.

Functional hydrophilic polystyrene beads with uniformly size and high cross-linking degree facilitated rapid separation of exenatide.

A high cross-linking polystyrene(PSt)-based anion-exchange material with uniformly size, high ion exchange capacity, and high hydrophilicity was synthesized by a novel surface functionalization approach in this study. Uniformly sized PSt microspheres were prepared by the membrane emulsion polymerization strategy, and then modified by (1) conversing resid ual surface vinyl groups to epoxy groups followed by quaternization, and (2) decorating aromatic ring matrix including nitration, reduction and attachment of glycidyltrimethylammonium chloride. The 3-D morphology and porous features of microspheres were observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The surface of the modified PSt became roughness but the particle size remained same. Meanwhile, FT-IR spectra and laser scanning confocal microscope (LCSM) indicated that the modification groups had been successfully covalently coated onto the PSt microspheres. Modified PSt microspheres showed greatly improved hydrophilicity and biocompatibility with 0.387mmol/mL ion exchange capacity (IEC). In the application evaluation procedure, exenatide can be purified from 42.9% (peptide crudes) to 88.6% by modified PSt column with 97.1% recovery yield. This modified PSt microspheres had a large potential in application for efficient separation of peptides.

Efficient decolorization and deproteinization using uniform polymer microspheres in the succinic acid biorefinery from bio-waste cotton (Gossypium hirsutum L.) stalks.

Bio-waste cotton (Gossypium hirsutum L.) stalks were converted into succinic acid by simultaneous saccharification and fermentation (SSF) using Actinobacillus succinogenes 130Z. After 54 h SSF at 40 °C and pH 7.0, the production of succinic acid was 63 g/L, with 1.17 g/L/h productivity and 64% conversion yield. After SSF, a simple method for the decolorization and deproteinization of crude SSF broth was developed through adsorption tests of polystyrene (PSt) microspheres. Under optimized conditions (5% PSt loading (w/v), pH 4.0, 60 °C and adsorption time of 40 min), the ratios of decolorization, deproteinization and succinic acid loss ratios were 96.6, 84.5 and 4.1%, respectively. The method developed will provide a potential approach for large-scale production of succinic acid from the biomass waste.

Porogen effects in synthesis of uniform micrometer-sized poly(divinylbenzene) microspheres with high surface areas.

A new method of synthesizing uniform poly(divinylbenzene) (polyDVB) microspheres with high specific surface areas was designed by combining Shirasu porous glass (SPG) membrane emulsification, suspension polymerization, and post-crosslinking techniques. It was shown that the physicochemical properties of porogens have a great influence on the size distribution and porous features of microspheres. The low aqueous solubility of porogen facilitated preparation of uniform emulsions and microspheres, and high aqueous solubility led to polydispersed emulsions and poor microsphere yields. Such aqueous solubility effects can be tailored by adding a low molecular weight polystyrene (LPST) as costabilizer in porogen, thus improving the uniformity of microspheres. Moreover, different affinities of porogens for copolymers demonstrate various contributions to specific surface areas of microspheres in suspension polymerization especially post-crosslinking. Solvating porogen requires a much higher addition than nonsolvating porogen to obtain equal specific surface areas in polymerization, but has more potential to enhance the specific surface area in post-crosslinking. Two kinds of uniform microspheres were obtained with high specific surface areas, up to 706.6 m2/g by heptane and 937.5 m2/g by toluene.