In vitroandin vivoevaluation of cyclodextrin-based nanosponges for enhancing oral bioavailability of atorvastatin calcium

Abstract

The aim of this study was to explore the feasibility of complexing the poorly water-soluble drug atorvastatin calcium (AC) with β-cyclodextrin (β-CD) based nanosponges (NS), which offer advantages of improving dissolution rate and eventually oral bioavailability. Blank NS were fabricated at first by reacting β-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2, 1:4, and 1:8), then NS of highest solubilization extent for AC were complexed with AC. AC loaded NS (AC-NS) were characterized for various physicochemical properties. Pharmacokinetic, pharmacodynamics and histological finding of AC-NS were performed in rats. The prepared AC-NS showed particles size ranged from 408.7 ± 12.9 to 423 ± 15.9 nm while zeta potential values varied from -21.7 ± 0.90 to -22.7 ± 0.85 mV. The loading capacity varied from 17.9 ± 1.21 to 34.1 ± 1.16%. DSC, FT-IR, and PXRD studies confirmed the complexation of AC with NS and amorphous state of the drug in the complex. AC-NS displayed a biphasic release pattern with increase in the dissolution rate of AC as compared to plain AC. Oral administration of AC-NS (1:4 w/w, drug: NS) to rats led to 2.13-folds increase in the bioavailability as compared to AC suspension. Pharmacodynamics studies in rats with fatty liver revealed significant reduction (p < .05) in total cholesterol, triglyceride, LDL-C and increased level of beneficial HDL-C along with improvement in the associated liver steatosis as confirmed through photomicrographs of liver sections. In this study, we confirmed that complexation of AC with NS would be a viable approach for improving oral bioavailability and in vivo performance of AC.

Evaluation of solubility enhancement, antioxidant activity, and cytotoxicity studies of kynurenic acid loaded cyclodextrin nanosponge

“…A significant difference in drug loading was observed in between 1:3 w/w and 1:4 w/w. However, no further change in drug loading was seen in between 1:4 w/w and 1:5 w/w might be due to saturation solubility of KYNA (Zidan et al, 2018).…”

“…KYNA loaded nanosponge was prepared by the freeze-drying method as established earlier (Zidan, Ibrahim, Afouna, & Ibrahim, 2018). An aqueous suspension of individual nanosponges (β-CDNS1 to β-CDNS3) was prepared (10 mg/ml) and the required quantity of KYNA was added into it at different weight ratio of 1:3, 1:4 and 1:5 (w/w), respectively.…”

Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

“…Nanosponge has a unique property of forming nanosuspension, when vapor is dispersed. 10 Paracetamol is world's most widely over-the-counter prescribed analgesic. It is the rst step of medication in the WHO pain scale, and is widely prescribed through many international recommendations as rst-line pharmacological treatment for acute and chronic painful conditions.…”

Cyclodextrin Nanosponges: A Promising Approach for Modulating Drug Delivery

“…The prepared nanosponges were found to increase bioavailability of drug up to 2.13-folds in comparison to its suspension. In addition, pharmacokinetic studies revealed remarkable decrease in total cholesterol, LDL-C (Low Density Lipoprotein Cholesterol) and triglyceride and improved level of HDL-C (High Density Lipoprotein Cholesterol) leading to improvement of liver steatosis [117].…”