Atorvastatin calcium loaded chitosan nanoparticles: in vitro evaluation and in vivo pharmacokinetic studies in rabbits

Abstract

In this study, we prepared atorvastatin calcium (AVST) loaded chitosan nanoparticles to improve the oral bioavailability of the drug. Nanoparticles were prepared by solvent evaporation technique and evaluated for its particle size, entrapment efficiency, zeta potential, in vitro release and surface morphology by scanning electron microscopy (SEM). In addition, the pharmacokinetics of AVST from the optimized formulation (FT5) was compared with marketed immediate release formulation (Atorva ® ) in rabbits. Particle size of prepared nanoparticles was ranged between 179.3 ± 7.12 to 256.8 ± 8.24 nm with a low polydispersity index (PI) value. Zeta potential study showed that the particles are stable with positive values between 13.03 ± 0.32 to 46.90 ± 0.49 mV. FT-IR studies confirmed the absence of incompatibility of AVST with excipient used in the formulations. In vitro release study showed that the drug release was sustained for 48 h. Results of pharmacokinetics study showed significant changes in the pharmacokinetic parameter (2.2 fold increase in AUC) of the optimized formulation as compared to marketed formulation (Atorva ® ). Thus, the developed nanoparticles evidenced the improvement of oral bioavailability of AVST in rabbit model. Uniterms:Atorvastatin calcium/oral bioavailability/experimental study. Atorvastatin calcium/in vitro release. Atorvastatin calcium/pharmacokinetics. Nanoparticles/drugs bioavailability.No presente estudo, preparamos nanopartículas de quitosana com atorvastatina cálcica (AVST) para melhorar a biodisponibilidade oral do fármaco. As nanopartículas foram preparadas pela técnica de evaporação de solvente, avaliando-se a granulometria, a eficiência de encapsulamento, o potencial zeta, a liberação in vitro e a morfologia da superfície, por meio da microscopia eletrônica de varredura (MEV). Além disso, a farmacocinética da formulação otimizada de AVST (FT5) foi comparada com a formulação comercial, de liberação imediata, comercializada (Atorva®), em coelhos. O tamanho das das nanopartículas variou na faixa de 179,3 a 256,8 ± 7,12 ± 8,24 nm, com baixo índice polidispersibilidade (PI). O estudo do potencial Zeta mostrou que as partículas são estáveis, com valores positivos entre 13,03 ± 0,32 a 46,90 ± 0,49 mV. Os estudos de FT-IR confirmaram a ausência de incompatibilidade de AVST com o excipiente utilizado nas formulações. O estudo de liberação in vitro mostrou que liberação sustentada do fármaco por 48 horas. Os resultados do estudo farmacocinético mostraram alterações significativas nos parâmetros (aumento de 2,2 vezes na ASC) da formulação otimizada em relação à comercializada (Atorva® ). Assim, o desenvolvimento de nanopartículas evidenciou a melhora da biodisponibilidade oral de AVST em coelhos.Uniterms: Atorvastatina cálcica/biodisponibilidade oral/estudo experimental. Atorvastatina cálcica/ liberação in vitro. Atorvastatina cálcica/farmacocinética. Nanopartículas/biodisponibilidade de fármacos.

Atorvastatin Solid Lipid Nanoparticles as a Promising Approach for Dermal Delivery and an Anti-inflammatory Agent

“…In contrast to our study which SLN was designed for dermal delivery, their SLN has been suitable for oral delivery. Most of the studies carried out on atorvastatin solid lipid nanoparticles have been for oral delivery ( 35 – 38 ) rather than dermal or transdermal delivery. Depending on the composition of SLN varying particle size, zeta potential, PDI, and EE% can be obtained ( 35 , 38 ).…”

<p>Chitosan-Coated PLGA Nanoparticles for Enhanced Ocular Anti-Inflammatory Efficacy of Atorvastatin Calcium</p>

“…From these results, we concluded that the release of AT from F1 follows a zeroorder, diffusion, and swelling mechanism. 38 More than one mechanism exerts a dominant effect on the release pattern of the drug from biodegradable polymeric systems; for example, diffusion-controlled release from the matrix of polymers is followed by readsorption, then the drug is desorbed from the surface of formed NPs, leading to degradation and dissolution/erosion of the polymeric network. 52 Nevertheless, drug release from the formed NPs is a combination of drug diffusion and surface erosion; CS forms a coat that acts as a physical barrier that swells or erodes, consequently restraining the release of drug from NPs.…”

“…All formulations followed non-Fickian anomalous diffusion-controlled mechanism since values of n≥0.5, indicating diffusion-controlled and swelling-controlled drug release. 15,16,38 The in vivo results may be due to the unparalleled properties of CS that formed the nanoparticles, 61 including bioadhesivity and penetration enhancement. CS carries a positive charge, so the bioadhesive property is due to its interaction with the negatively charged mucin on the eye surface.…”

Tissue Engineered Bio‐Blood‐Vessels Constructed Using a Tissue‐Specific Bioink and 3D Coaxial Cell Printing Technique: A Novel Therapy for Ischemic Disease

“…The mass of released atorvastatin was quantified using a spectrometer (Epoch 2 Microplate Spectrophotometer, BioTek, VT, USA) by checking the absorbance at 264 nm against appropriate standards. [31] Murine Hindlimb Ischemia Model: Experiments were performed on male eight-week-old BALB/c nude mice (Biogenomics, Seoul, Korea) maintained under a 12 h light/dark cycle and in accordance with the regulations of the Pusan National University. All procedures were performed in accordance with the policies of the Institutional Animal Care and Use Committee of the Pusan National University of Korea (IACUC090017).…”