Obesity is the major cause of type 2 diabetes with hyperlipidemia as one of its complications and antioxidants were found to be beneficial in such disease conditions. The present investigation is geared towards reduction of the dose required/improve the bioavailability of the combination of antioxidants, ellagic acid and coenzyme Q10 by co-encapsulating them into nanoparticles and study the possible synergism in ameliorating hyperlipidemia in high fat diet fed rats. The co-encapsulated particles at 10% (w/w of polymer) loading of ellagic acid and coenzyme Q10 have particle size of 260 nm. Male Sprague-Dawley (SD) rats on feeding high fat diet for over 4 weeks developed hyperlipidemia. The hyperlipidemic rats on 2 weeks post treatment with antioxidant combination administered as oral suspension or nanoparticles found to ameliorate the hyperlipidemic conditions and nanoparticles were found to be equally/more effective at 3 times lower dose in sustaining cholesterol lowering effect for extended periods, lowering glucose and triglycerides and in improving endothelial functioning, indicating the ability of the nanoparticles in improving efficacy of the duo. The results promise the potential of nanoparticles in improving the efficacy of ellagic acid and coenzyme Q10 in treating high fat diet induced hyperlipidemia in rats.
Atorvastatin calcium (AC) is a second-generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor approved for clinical use as a lipid lowering agent. AC, the world's best selling drug is associated with poor oral bioavailability and serious adverse effects like rhabdomyolysis on chronic administration. A biodegradable nanoparticulate approach was introduced here with a view to improving the efficacy and safety of AC. Poly lactide-co-glycolic acid (PLGA) nanoparticles containing atorvastatin calcium were prepared using two stabilizers i.e. didodecyl dimethyl ammonium bromide (DMAB) and Vitamin E tocopheryl polyethylene glycol 1000 succinate (Vit E-TPGS) using a co-solvent approach by emulsion-diffusion-evaporation method. AC loaded PLGA nanoparticles prepared using DMAB and Vit E-TPGS were found to be 120.0 +/- 4.2 nm and 140.0 +/- 1.5 nm (z-average) in size respectively. In vitro release studies at pH 7.4 revealed a zero order release profile for nanoparticles. Efficacy and safety parameters of the prepared nanoparticles against marketed formulation were evaluated in high fat diet fed (hyperlipidemic) rats. It was found that atorvastatin calcium nanoparticles were equally effective in comparison to Lipicure, at a 66%-reduced dose in treating the hyperlipidemia characterized by alterations in PTC, LDL-C, VLDL-C, HDL-C, PTG and PGL in the high fat diet fed rats. On the other hand, when evaluated for safety, nanoparticulate formulation showed no/negligible myotoxicity characterized by lower PC, BUN, CK, LDH and AST levels in comparison to the marketed formulation.
Most of the new chemical entities (NCEs) are poorly water-soluble and pose a challenge to developing an optimum solid oral dosage form. Oral route has been the major route of drug delivery for the treatment of various diseases. Delivery of poorly water--soluble molecules by oral route is difficult because approximately 40 % of drug compounds are limited to low aqueous solubility, which leads to restricted oral bioavailability, high intra-and inter-subject variability and lack of dose proportionality (1).To increase the oral bioavailability of poorly water-soluble compounds and eliminate the discussed drawbacks, various other formulation strategies have been adopted, including the use of cyclodextrins, nanoparticles, solid dispersions and permeation en- The aim of the study was to develop and evaluate a self--emulsifying drug delivery system (SEDDS) formulation to improve solubility and dissolution and to enhance systemic exposure of a BCS class II anthelmetic drug, albendazole (ABZ). In the present study, solubility of ABZ was determined in various oils, surfactants and co-surfactants to identify the microemulsion components. Pseudoternary phase diagrams were plotted to identify the microemulsification existence area. SEDDS formulation of ABZ was prepared using oil (Labrafac Lipopfile WL1349) and a surfactant/co-surfactant (Tween 80/PEG 400) mixture and was characterized by appropriate studies, viz., microemulsifying properties, droplet size measurement, in vitro dissolution, etc. Finally, PK of the ABZ SEDDS formulation was performed on rats in parallel with suspension formulation. It was concluded that the SEDDS formulation approach can be used to improve the dissolution and systemic exposure of poorly water-soluble drugs such as ABZ.
A highly sensitive and specific LC-MS/MS-ESI method was developed for simultaneous quantification of albenadazole (ABZ) and ricobendazole (RBZ) in rat plasma (50 μL) using phenacetin as an internal standard (IS). Simple protein precipitation was used to extract ABZ and RBZ from rat plasma. The chromatographic resolution of ABZ, RBZ and IS was achieved with a mobile phase consisting of 5 m m ammonium acetate (pH 6) and acetonitrile (20:80, v/v) at a flow rate of 1 mL/min on a Chromolith RP-18e column. The total chromatographic run time was 3.5 min and the elution of ABZ, RBZ and IS occurred at 1.66, 1.50 and 1.59 min, respectively. A linear response function was established for the ranges of concentrations 2.01-2007 and 6.02-6020 ng/mL for ABZ and RBZ, respectively. The intra- and inter-day precision values for ABZ and RBZ met the acceptance as per FDA guidelines. ABZ and RBZ were stable in battery of stability studies, viz. bench-top, auto-sampler and freeze-thaw cycles. The developed assay was applied to a pharmacokinetic study in rats.
Purpose: To evaluate a new surgical technique (“prick and print”) for harvesting shaped donor corneal grafts in cases with perforated peripheral ulcerative keratitis (PUK). Methods: We conducted a retrospective case series at a tertiary center. Medical records of 13 patients with perforated PUK, who underwent tectonic eccentric keratoplasty using the stenciling-based prick and print technique during the past 1 year, were reviewed. All patients (15 eyes of 13 patients) received grafts of varying sizes and shapes (14 crescentic and 1 biconvex). Factors evaluated were tectonic integrity, graft apposition, and complications, if any. Surgical success was defined as maintenance of corneal integrity and healing of PUK. Results: Mean age of patients was 40.6 ± 19.4 years. Mean follow-up was 10 months. We achieved surgical success in 80% (12/15 eyes) of cases. Two eyes had graft infection, and regrafting (large circular graft) was performed for both. One eye developed new-site PUK, which was managed medically, and the graft remained viable tectonically. After surgery, 9 eyes achieved a best-corrected visual acuity of logarithm of the minimum angle of resolution +0.3 or better. No cases had graft rejection or peripheral anterior synechiae by final follow-up. Conclusions: The stenciling-based prick and print technique for making shaped donor corneal grafts may offer a simple, easy-to-learn surgical technique that can be used to make any shape or pattern of donor corneal grafts without involving the optical center, even in extensive peripheral corneal lesions.
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