Multidimensional isotope analysis of carbon, hydrogen, and oxygen as a tool for traceability of lactose in drug products.

Lactose is one of the most commonly used pharmaceutical excipients. Depending on manufactures, the properties of lactose are very different, which could impact the pharmacokinetic behavior of drug products. Therefore, it is very important to trace the origin of pharmaceutical lactose in drug products which is valuable for prescription analysis. In this study, the carbon, hydrogen and oxygen isotope ratios (δ13C, δ2H and δ18O) of thirty-four lactose from seven manufacturers were analyzed by elemental analysis-stable isotope ratio mass spectrometry (EA-IRMS). One-way analysis of variance (ANOVA) and Duncan's test indicated significant differences in isotope ratios of lactose from different origins. To identify the lactose manufacturer, a discrimination model was generated through linear discriminant analysis (LDA). Based on this model, the manufacturers of lactose used in three drug products were successfully identified. Our results suggested that the multidimensional analysis of δ13C, δ2H and δ18O of lactose provided a fast and effective method to trace the lactose manufacturer. In conclusion, this method can be used to analyze the prescription of the drug product quickly, which could speed up the development of generic drug product.

Electrostatic Attraction-Driven Assembly of a Metal-Organic Framework with a Photosensitizer Boosts Photocatalytic CO2 Reduction to CO.

Reducing CO2 into fuels via photochemical reactions relies on highly efficient photocatalytic systems. Herein, we report a new and efficient photocatalytic system for CO2 reduction. Driven by electrostatic attraction, an anionic metal-organic framework Cu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) as host and a cationic photosensitizer [Ru(phen)3]2+ (phen = 1,10-phenanthroline) as guest were self-assembled into a photocatalytic system Ru@Cu-HHTP, which showed high activity for photocatalytic CO2 reduction under laboratory light source (CO production rate of 130(5) mmol g-1 h-1, selectivity of 92.9%) or natural sunlight (CO production rate of 69.5 mmol g-1 h-1, selectivity of 91.3%), representing the remarkable photocatalytic CO2 reduction performance. More importantly, the photosensitizer [Ru(phen)3]2+ in Ru@Cu-HHTP is only about 1/500 in quantity reported in the literature. Theoretical calculations and control experiments suggested that the assembly of the catalysts and photosensitizers via electrostatic attraction interactions can provide a better charge transfer efficiency, resulting in high performance for photocatalytic CO2 reduction.

[Enhancement of gastrointestinal absorption of chitosan-coated insulin-loaded poly (lactic-co-glycolic acid) nanoparticles].

AIM: To study chitosan-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on enhancing gastrointestinal absorption of insulin. METHODS: Insulin-loaded PLGA multiple emulsions were prepared by a double-emulsion method. Using chitosan as a stabilizer, chitosan-coated PLGA-NPs was prepared. The changes of the morphology, size distribution and Zeta potential of the NPs were examined. The encapsulation efficiency was determined by HPLC. The release behaviors in vitro were assessed, and the hypoglycemic effects were evaluated by monitoring the glucose levels in diabetic rats. RESULTS: Chitosan-coated PLGA-NPs showed a narrow size of distribution and regular surface with layer structure and their Zeta potential can be changed by chitosan. Chitosan-coating increased the encapsulation efficiency of insulin, reduced the initial burst and improved the release behavior of the NPs. About 14-16 h after intragastric administration of chitosan-coated INS-PLGA-NPs, the plasma glucose level decreased significantly compared with intragastric administration of same dose of non-coated NPs (P < or = 0.05), and the relative pharmacological availability was increased up to (15.4 +/- 1.2)%. CONCLUSION: Chitosan-coated PLGA-NPs could enhance gastrointestinal absorption of insulin.

Relationship between drug effects and particle size of insulin-loaded bioadhesive microspheres.

AIM: To formulate and characterize insulin-loaded adhesive microspheres (MP) and evaluate drug effects of MP with various sizes, 120, 350, and 1000 nm in diameter, in the alloxan-induced diabetic rats. METHODS: Insulin-loaded MP were formulated by an ionotropic gelation procedure. Particle size distributions were determined by photon correlation spectroscopy and optical microscopy. The factors that influenced the particle sizes and loading capacity were investigated, and the release properties were assessed in vitro. The hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration. RESULTS: All the MPs with three sizes formulated were in the desired size range, and the loading capacity was 15.3 %+/-1.7 % (120 nm), 32.4 %+/-2.4 % (350 nm), and 53.3 %+/-2.7 % (1000 nm) respectively. The particle size also had an influence on the release property of the MPs. Half an hour later, 25 %+/-4 % (120 nm), 18.3 %+/-2.4 % (350 nm), and 8.6 %+/-1.3 % (1000 nm) of insulin were released. MP with different sizes had various degree of hypoglycemic effects after 10 h (P<0.05 vs control insulin solution). The plasma glucose level of 350 nm size particles remarkably decreased 15 h later (P<0.05 vs 120 nm) or 35 h later (P<0.01 vs others). The relative pharmacological availability was 10.2 %+/-0.5 % (120 nm), 14.9 %+/-1.3 % (350 nm), and 7.3 %+/-0.8 % (1000 nm) respectively. Particles of 350 nm showed a comparatively higher availability (P<0.05). CONCLUSION: Adhesive CS-MP were helpful in increasing the relative pharmacological bioavailability of insulin, and a distinct advantage of proper particle size helped to increase the drug effects.

Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo.

There are many ongoing investigations to improve the oral bioavailability of peptide and protein formulations. Bioadhesive polysaccharide chitosan nanoparticles (CS-NPs) would seem to further enhance intestinal absorption of them. In this study, Insulin-loaded CS-NPs were prepared by ionotropic gelation of CS with tripolyphosphate anions. Its particle size distribution and zeta potential were determined by photon correction spectroscopy and laser Dopper anemometry. The ability of CS-NPs to enhance intestinal absorption of insulin and increase the relative pharmacological bioavailability of insulin was investigated by monitoring the plasma glucose level of alloxan-induced diabetic rats after oral administration of various doses of insulin-loaded CS-NPs. CS-NPs had a particle size in the range of 250-400 nm and its polydispersity index was smaller than 0.1, positively charged, stable. Insulin association was found up to 80% and its in vitro release showed a great initial burst with a pH-sensitivity property. CS-NPs enhanced the intestinal absorption of insulin to a greater extent than the aqueous solution of CS in vivo. Above all, after administration of 21 I.U./kg insulin in the CS-NPs, the hypoglycemia was prolonged over 15 h and the average pharmacological bioavailability relative to SC injection of insulin solution was up to 14.9%.