Cellulose nanocrystals modification by grafting from ring opening polymerization of a cyclic carbonate.

Surface modification of cellulose nanocrystals (CNC) by organocatalysed grafting from ring-opening polymerization (ROP) of trimethylene carbonate was investigated. Organocatalysts including an amidine (DBU), a guanidine (TBD), an amino-pyridine (DMAP) and a phosphazene (BEMP) were successfully assessed for this purpose, with performances in the order TBD > BEMP > DMAP, DBU. The grafting ratio can be tuned by varying the experimental parameters, with the highest grafting of 74 % by weight obtained under mild conditions, i.e at room temperature in tetrahydrofuran with a low amount of catalyst. This value is much higher than that of typical ring opening polymerizations of cyclic esters initiated from the surface of cellulose nanoparticles. Additionally, DSC analysis of the modified material revealed the presence of a glass transition temperature, indicative of a sufficient graft length to display polymeric behaviour. This is, to our knowledge, the first example of cellulose nanocrystals grafted with polycarbonate chains.

Novel bicephalous heterolipid based self-microemulsifying drug delivery system for solubility and bioavailability enhancement of efavirenz.

There is an increasing demand for new lipidic biocompatible and safe materials for self-microemulsifying drug delivery system (SMEDDS). The present work reports the synthesis, characterization, oral mucosal irritation study, and application of novel erucic acid ester of G0-PETIM dendron based bicephalous heterolipid (BHL) as an oil phase in SMEDDS using Efavirenz (EFA), a BCS class II drug with poor water solubility and poor bioavailability. Studies were conducted to optimize EFA SMEDDS using different ratios of the BHL as oil phase and surfactant: co-surfactant weight ratios (Km). At Km (1.5), the microemulsion was spontaneously formed in water with mean globule size of 22.78 ±â€¯0.25 nm and polydispersity index (PDI) of 0.23 ±â€¯0.031 with high drug loading efficiency of 80.35 ±â€¯3.1%. Standard stability tests were performed on EFA SMEDDS and the results indicated it to be highly stable. The in vitro dissolution profile of EFA SMEDDS showed >95% of the drug release within an hour and expectedly substantial enhancement in in vivo bioavailability was observed; almost 6-fold increase in bioavailability with parameters Cmax 5.2 µg/mL, Tmax 3 h, and AUC(0-∞) 23.48 µg/h/mL respectively as compared the plain suspension of the drug. In conclusion, the BHL can be used effectively as an oil phase in SMEDDS to enhance solubility and bioavailability of BCS Class II drugs. Further, it holds, in general, a great promise as a new excipient for solubility and bioavailability enhancements.

Sulfated modification of the polysaccharides from blackcurrant and their antioxidant and α-amylase inhibitory activities.

Sulfated modification was conducted to modify a homogenous polysaccharide from blackcurrant (BCP). The sulfated polysaccharides (SBCPs) with different degree of substitution (DS) were synthesized using the aminosulfonic acid (ASA)/4-dimethylaminopyridine method by varying reaction conditions such as the mass ratio of ASA to BCP, temperature, and time. Three sulfated derivatives were chosen for high-performance gel-permeation chromatography, gas chromatography, fourier-transform infrared (FT-IR) spectroscopy, and nuclear magnetic resonance (NMR), and activity studies, designated as SBCP-1, SBCP-2, and SBCP-3 with DS of 1.28, 0.95, and 0.53, respectively. Results showed that the sulfated modification was successful, and SBCPs had an increase in molecular weight compared to BCP. Both SBCPs and BCP were composed of rhamnose, arabinose, xylose, mannose, galactose, and glucose, with different molar ratios. Sulfate substitution was further confirmed by FT-IR and 13C NMR analysis. SBCPs exhibited excellent antioxidant capacities (DPPH, hydroxyl, and superoxide radical scavenging, reducing power, and ferrous metal-chelating capacities) and α-amylase inhibitory activity in vitro, and the activities of SBCPs were significantly improved in positive correlation with the DS value. This study suggested that SBCPs could serve as potential antioxidant agents to be used as alternative supplements or functional foods.

Antimicrobial metabolites from the plant endophytic fungus Penicillium sp.

Five rare dichloro aromatic polyketides (1-5) were obtained from an endophytic fungus Penicillium sp., along with five known metabolites (6-10). Their structures were elucidated by extensive spectroscopic analysis, Mosher methods, as well as [Rh2(OCOCF3)4]-induced electronic circular dichroism (ECD) experiments. Compounds 2-4 and 6 structurally involved acyclic 1.3-diols, the uneasy configuration determinations of which were well carried out by double-derivation NMR methods. Compounds 1-10 were evaluated for their antibacterial and antifungal activities against five strains of human pathogenic microorganisms. Helvolic acid (7) showed potent inhibitory effects against Staphylococcus aureus and Pseudomonas aeruginosa with MIC (minimum inhibitory concentration) values of 5.8 and 4.6µg/mL, respectively.

pH-sensitive polymeric micelles formed by doxorubicin conjugated prodrugs for co-delivery of doxorubicin and paclitaxel.

A doxorubicin conjugated prodrug incorporated acid-sensitive linkage between drug and Pluronic F127-chitosan (F127-CS) polymer was successfully synthesized. Subsequently a pH-sensitive polymeric micelle system was designed based on the conjugated prodrugs (F127-CS-DOX) to co-deliver doxorubicin and paclitaxel. Paclitaxel (PTX) was physically entrapped in the hydrophobic inner core of the micelles simultaneously. The structures of conjugates were analyzed by means of (1)H NMR and UV-vis spectrum. Size distribution and morphology of the micelles were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results indicated that obtained micelles had good dispersity and the diameter was between 56.3 and 403.4 nm. The loading of PTX into the micelle increased with higher DOX content. DOX and PTX release from polymeric micelles followed an acid-triggered manner. Furthermore, in vivo pharmacokinetic study also showed that the area under the plasma concentration time curve (AUC0-∞) values of PTX and DOX for PTX-loaded F127-CS-DOX micelles in rats were 3.97 and 4.38-fold higher than those for PTX plus DOX solution. These results suggested the PTX-loaded F127-CS-DOX micelles would be a promising carrier for co-delivering DOX and PTX.

Pomelo peel modified with acetic anhydride and styrene as new sorbents for removal of oil pollution.

Pomelo peel (PP), as one of the well-known agricultural wastes, is cost-effective and environmentally friendly. Based on PP, two new kinds of oil sorbents were prepared by using acetic anhydride and styrene. The structures of raw pomelo peel (RP), acetic anhydride-treated pomelo peel (AP) and styrene-treated pomelo peel (SP) were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), contact-angle (CA) measurements. The optimum reaction conditions for preparation of AP and SP were also investigated. The resulting products exhibited better oil sorption capacity than that of RP for diesel and lubricating oil, also SP had better oil sorption capacity than AP, while the oil sorption capacities of SP for diesel and lubricating oil reached 18.91 and 26.36 g/g, respectively. Adsorption kinetics was well described by the pseudo-second-order model. The results indicated that AP and SP, especially SP could be used as the substitute for non-biodegradable oil sorption materials.

Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates.

Antibody-drug conjugates (ADCs), combining monoclonal antibody with high cytotoxicity chemotherapeutic drug (warhead), have been successfully applied for clinical cancer therapy. Linker technology to select and design linker connecting warhead with antibody, is critical to the success of therapeutic ADCs. In this study, three kinds of linkers were designed to connect SN-38, the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100-1000 times more potent than CPT-11, with the anti-HER2 antibody trastuzumab to prepare three different ADC conjugates (T-SN38 A, B and C). Meanwhile, we compared the anti-ovarian cancer effect of these three T-SN38 conjugates with trastuzumab in vitro and in vivo. Our in vitro results showed that T-SN38 A, B and C (drug-to-antibody ratio, DAR=3.7, 3.2, 3.4) were 2 to 3 times as cytotoxic as SN-38, and the IC50 for these three conjugates on SKOV-3 cell line at 72 h were 5.2 ± 0.3, 4.4 ± 0.7, and 5.1 ± 0.4 nM respectively. In our in vivo studies, T-SN38 conjugates had well targeting ability for tumor tissue and all three of them had much higher anti-ovarian cancer potency than trastuzumab. Among of them, T-SN38 B, which coupled SN-38 with trastuzumab by a carbonate bond, has the best anti-ovarian cancer potency. In conclusion, the novel HER2-targeting ADCs T-SN38 have great potential for HER2-positive ovarian cancer. Moreover, the SN-38-Linkers designed in this study can also be used to connect with other antibodies for the therapy of other cancers.

Hepatoprotective agent tethered isoniazid for the treatment of drug-induced hepatotoxicity: Synthesis, biochemical and histopathological evaluation.

The aim of the study was to investigate the protective effect of isoniazid-curcumin conjugate (INH-CRM) in INH-induced hepatic injury by biochemical analysis and histology examination of liver in Wistar rats. The biochemical analysis included determination of the levels of plasma cholesterol, triglycerides (TG), albumin content, and lipid peroxidation (MDA). INH-CRM administration resulted in a significant decrease in plasma cholesterol, TG, and MDA levels in the liver tissue homogenate with an elevation in albumin level indicating its hepatoprotective activity. Histology of the liver further confirmed the reduction in hepatic injury. The hepatoprotective with INH-CRM can be attributed to the antioxidant activity of curcumin. The conjugate probably stabilizes the curcumin molecule, preventing its presystemic metabolism thereby enhancing its bioavailability and therefore, its hepatoprotective activity. Thus, the novel INH-CRM has the potential to alleviate INH-induced liver toxicity in antitubercular treatment.

A co-delivery system based on paclitaxel grafted mPEG-b-PLG loaded with doxorubicin: preparation, in vitro and in vivo evaluation.

Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX·HCl) based on methoxypoly(ethylene glycol)-block-poly(L-glutamic acid) (mPEG-b-PLG) for cancer treatment. PTX was grafted to the mPEG-b-PLG by esterification to give mPEG-b-PLG-g-PTX. DOX·HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX·HCl and mPEG-b-PLG-g-PTX in aqueous solution. The release rate of DOX·HCl from the drug-loaded nanoparticles (mPEG-b-PLG-g-PTX-DOX) was slow at blood pH (pH 7.4), but obviously increased at endosome pH (pH 5.4). The mPEG-b-PLG-g-PTX-DOX exhibited slight synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG-b-PLG-g-PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a 95.5% tumor-suppression-rate which was significantly higher than those of related single anticancer agents such as free DOX·HCl and mPEG-b-PLG-g-PTX. These results indicated that the mPEG-b-PLG-g-PTX-DOX would have great potential in cancer therapy.