Enteric coating of nanostructured lipid carriers (NLCs) and enteric coating of hard gelatin capsules filled with NLCs: Feasibility studies.

Nanostructured lipid carriers (NLCs) of asenapine maleate (ASPM) were enteric coated with polymethacrylate polymers (Eudragit®) for oral delivery. The present study aimed to compare the feasibility of direct enteric coating of NLCs and enteric coating of hard gelatin capsules filled with lyophilized ASPM-NLCs. Organic solution of Eudragit® was prepared using acetone containing 3% v/v water, acetone or ethanol. Aqueous dispersion of Eudragit® was obtained by neutralization with base. Capsules were enteric coated by dip-coating method with 3:2 ratio of Eudragit® L100-55:S100 (7.5-12.5% w/v). ASPM-NLCs showed particle size of 84.91±2.14nm, polydispersity index of 0.222±0.026, entrapment efficiency of 86.9±1.8% and zeta potential of -4.83±0.29 mV. TEM images showed good sphericity of the particles with the size of ≈100nm. Non-aqueous enteric coating was not successful as NLCs were precipitated in organic solvent. Aqueous enteric coated ASPM-NLCs (lipid:coat=1:2) showed an increased size (150.8±16.7nm) and zeta potential (-23.5±2.2 mV) revealing the deposition of Eudragit®. However, aqueous enteric coated ASPM-NLCs and uncoated ASPM-NLCs showed higher drug release (18.3±3.1-22.3±3.2%) in HCl solution (pH 1.2) indicating no resistance offered by direct enteric coating of NLCs; whereas enteric coated capsules showed less drug release (4.7±0.8%) in HCl solution indicating sufficient gastric protection.

Supplementation of biotin to sperm preparation medium enhances fertilizing ability of spermatozoa and improves preimplantation embryo development.

PURPOSE: Motility of spermatozoa helps not only in planning the type of infertility treatment but also directly reflects the success rate in assisted reproductive technology (ART). Previously, biotin, a water-soluble vitamin, has been shown to increase the motility and longevity of cryopreserved human spermatozoa. The present study was designed to understand the molecular basis of the beneficial effects of presence of biotin in sperm wash medium on early embryo development. METHODS: The effect biotin supplementation to sperm wash medium on the sperm parameters were assessed in swim-up fraction of normozoospermic and asthenozoospermic ejaculates collected from infertile men. Fertilization and early embryo development was studied using Swiss albino mice. RESULTS: Even though both biotin and pentoxifylline (PTX) enhanced the motility of spermatozoa from normozoospermic and asthenozoospermic samples, biotin group exhibited higher in vitro survival. Using mouse model, we observed that presence of biotin or PTX in sperm wash medium improved the fertilization rate and blastocyst rate compared to control. Blastocysts from these groups had significantly higher total cell number (P < 0.01) and lower apoptotic index. In silico target prediction revealed that GTPase HRas (HRas), tyrosine-protein phosphatase nonreceptor type 1 (PTP1B), and glucokinase are the probable targets for biotin. Solution-state Nuclear Magnetic Resonance (NMR) studies confirmed that biotin interacts both with human HRas and PTP1B. CONCLUSION: Our results indicate that presence of biotin in sperm wash medium can improve the fertilization potential and preimplantation embryo development and can be considered as a safe alternate to PTX.

Active Targeting of Drugs and Bioactive Molecules via Oral Administration by Ligand-Conjugated Lipidic Nanocarriers: Recent Advances.

The oral route is the most widely accepted and commonly used route for administration. However, this route may not be suitable for certain drug candidates which suffer from the problem of low aqueous solubility and gastrointestinal absorption and extensive first-pass effect. Nanotechnology-based approaches can be taken up as remedies to overcome the disadvantages associated with the oral route. Among the various nanocarriers, lipidic nanocarriers are widely used for oral delivery of bioactive molecules owing to their several advantages. Active targeting of bioactive molecules via lipidic nanocarriers has also been widely attempted to improve oral bioavailability and to avoid first-pass effect. This active targeting approach involves the use of ligands grafted or conjugated onto a nanocarrier that is specific to the receptors. Active targeting increases the therapeutic efficacy as well as reduces the toxic side effects of the drug or bioactive molecules. This review mainly focuses on the challenges involved in the oral delivery of drugs and its approaches to overcome the challenges using nanotechnology, specifically focusing on lipidic nanocarriers like liposomes, solid lipid nanoparticles, and nanostructured lipid carriers and active targeting of drug molecules by making use of ligand-conjugated lipidic nanocarriers.

Targeting the intestinal lymphatic system: a versatile path for enhanced oral bioavailability of drugs.

INTRODUCTION: The major challenge of first pass metabolism in oral drug delivery can be surmounted by directing delivery toward intestinal lymphatic system (ILS). ILS circumvents the liver and transports drug directly into systemic circulation via thoracic duct. Lipid and polymeric nanoparticles are transported into ILS through lacteal and Peyer's patches. Moreover, surface modification of nanoparticles with ligand which is specific for Peyer's patches enhances the uptake of drugs into ILS. Bioavailability enhancement by lymphatic uptake is an advantageous approach adopted by scientists today. Therefore, it is important to understand clear insight of ILS in targeted drug delivery and challenges involved in it. AREAS COVERED: Current review includes an overview of ILS, factors governing lymphatic transport of nanoparticles and absorption mechanism of lipid and polymeric nanoparticles into ILS. Various ligands used to target Peyer's patch and their conjugation strategies to nanoparticles are explained in detail. In vitro and in vivo models used to assess intestinal lymphatic transport of molecules are discussed further. EXPERT OPINION: Although ILS offers a versatile pathway for nanotechnology based targeted drug delivery, extensive investigations on validation of the lymphatic transport models and on the strategies for gastric protection of targeted nanocarriers have to be perceived in for excellent performance of ILS in oral drug delivery.

Characterization of the Phenolic Compound, Gallic Acid from Sansevieria roxburghiana Schult and Schult. f. Rhizomes and Antioxidant and Cytotoxic Activities Evaluation.

BACKGROUND: Sansevieria roxburghiana Schult. and Schult. f. (Asparagaceae) grows in India, Indonesia, Sri Lanka, and tropical Africa. Even though the plant has been traditionally used for the treatment of many ailments, the antioxidant and antiproliferative activities of S. roxburghiana methanol extract and its fractions have not yet been explored. MATERIALS AND METHODS: Quantitative estimation of phenols and different antioxidant assays were performed using standard methods. Anti-proliferative effect of the extract and fractions were evaluated in HCT-116, HeLa, MCF-7, HepG2, and A-549 cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assay methods. High-performance liquid chromatography (HPLC) and high-performance thin layer chromatography (HPTLC) fingerprint profiling were carried out for extract and different fractions. RESULTS: Significant antioxidant and anti-proliferate activity were detected in ethyl acetate fraction. Ethyl acetate fraction showed prominent scavenging activity in 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, and nitric oxide antioxidant assays with an concentration yielding 50% inhibition (IC50) 15.33 ± 1.45, 45.3 ± 1.93 and 48.43 ± 0.46 mg/ml, respectively. Cytotoxicity of ethyl acetate fraction was the highest among other fractions against HCT-116, HeLa, and MCF-7cancer cell lines with IC50 values 16.55 ± 1.28, 12.38 ± 1.36, and 8.03 ± 1.9 µg/ml, respectively, by MTT assay and 15.57 ± 0.70, 13.19 ± 0.49, and 10.34 ± 0.9 µg/ml, respectively, by SRB assay. The presence of gallic acid in the ethyl acetate fraction of S. roxburghiana rhizomes was confirmed by HPLC and HPTLC analysis. CONCLUSION: Results suggested that ethyl acetate fraction exhibited effective antioxidant and antiproliferative activities. The phenolic compounds identified in ethyl acetate fraction could be responsible for the activities. SUMMARY: Sansevieria roxburghiana has been selected for in vitro antioxidant and cytotoxicity screeningEthyl acetate fraction of methanol extract of S. roxburghiana exhibited effective antioxidant and antiproliferative activitiesThe activity of ethyl acetate fraction may be due to the presence of phenolic compound which is identified by high-performance liquid chromatography and high-performance thin layer chromatography techniques. Abbreviations used: %: Percent, ºC: Celsius, mg: Microgram, ml-Microlitre, ANOVA: Analysis of variance, DMSO: Dimethyl sulfoxide, g: Grams, IC50: Concentration yielding 50% inhibition, Kg: Kilogram, mg: Milligram, min: Minutes, ml: Milliliter, HPLC: High-performance liquid chromatography, HPTLC: High-performance thin layer chromatography, DPPH: 1,1-diphenyl-2-picrylhydrazyl, ABTS: 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, GAE: Gallic acid equivalents, SRME: Methanol extract of S. roxburghiana, ROS: Reactive oxygen species, SRPE: Petroleum ether fraction of S. roxburghiana, SREA: Ethyl acetate fraction of S. roxburghiana, SRAQ: Aqueous fraction of S. roxburghiana, DMEM: Dulbecco's Minimum Essential Medium, FBS: Fetal bovine serum, OD: Optical density, TPC: Total phenolic content, SRBU: Butanol fraction of S. roxburghiana.