Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems

Abstract

A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to highlight the importance of the lipid composition, with cyclosporine A (CyA) as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs), and self-microemulsifying drug-delivery systems (SMEDDS) were prepared. The particle size of PLGA NPs (182.2±12.8 nm) was larger than that of NLCs (89.7±9.0 nm) and SMEDDS (26.9±1.9 nm). All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%±1.6% and 80.3%±0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral ® , according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral ® . However, PLGA NPs failed to achieve efficient absorption, with relative bioavailability of about 22.7%. It is concluded that lipid-based nanoscale drug-delivery systems are superior to polymeric NPs in enhancing oral bioavailability of poorly water-soluble and poorly permeable drugs.

Development, Characterization, and Pharmacokinetic Evaluation of a CRV431 Loaded Self-Microemulsifying Drug Delivery System

“…The mean particle diameter of the CRV431 SMEDDS formulation when dispersed in water was measured to be 24.6 ± 5.7 nm (mean ± standard deviation) ( Figure 5). This size is consistent with the reported particle size of Neoral® aqueous dispersions (17).…”

“…The oil phase and co-solvent being the primary driver of drug solubility while the surfactant being the primary driver of microemulsion formation due to its amphoteric properties. The commercial CsA SMEDDS (Neoral®) contains a surfactant and oil combination with several co-solvents which disperse quickly in water with a particle size of approximately 30 nm (17). Neoral® is highly solubilizing for CsA (> 100 mg/ml) and results in good blood exposure (18).…”

<p>In vitro Characterization and Release Studies of Combined Nonionic Surfactant-Based Vesicles for the Prolonged Delivery of an Immunosuppressant Model Drug</p>

“…The F 10 and CsA aqueous dispersion were respectively administered to rabbits by oral route at an equivalent dose of 10 mg/kg CsA. 23 , 24 Single dose (non-crossover design) was used for in vivo study of optimized niosomal preparations. Twelve healthy male albino rabbits weighing 1.2–1.6 Kg (average weight of 1.5 Kg) were chosen.…”

“…After collecting blood samples the rabbits were reverted to their appropriate cages. 23 A simple and rapid HPLC method was used for estimation of CsA in rabbit plasma. The Agilentz1200 series HPLC technique was employed to analyze CsA.…”

<p>Cholate-modified polymer-lipid hybrid nanoparticles for oral delivery of quercetin to potentiate the antileukemic effect</p>

“…This study shows that PLNs substantially improve the oral absorption of QUE. But, the oral delivery efficacy of plain PLNs is not sufficient if simply through the nanoscale effect of nanocarriers,35 which involves an increase in the absorption area and nonspecific transmembrane transport (cytosis). Endowing nanoparticles with an active transport represents an important approach to augment the absorption degree of encapsulated drugs.…”