ABSTRACT
The present work aims at improving stability of paclitaxel (PTX) loaded liposomes by its coating with silica on the surface by a modified sol-gel method. Effect of various components of liposomes such as phosphatidylcholine to cholesterol ratio (PC:CH), PTX and stearylamine on entrapment efficiency (% EE) and particle size were systematically investigated and optimized using central composite design on Design-Expert®. The optimized liposomes were utilized as a template for silica coating to prepare surface coated PTX liposils. Physical stability of liposomes and liposils was evaluated with Triton X-100 and the results indicated that liposils were much more stable as compared to liposomes and the same has been reiterated in stability study performed over 6â¯months. In vitro cytotoxicity study on B16F10 tumor cells showed cytotoxicity of PTX liposils was not significantly different than PTX liposomes, whereas both were less cytotoxic as compared to the commercial Taxol®. In vivo pharmacokinetics on rats, exhibited increased T1/2 of liposils when compared to liposomes and Taxol®, thus releasing the drug over a longer duration. The enhanced physicochemical stability as well as controlled release of PTX in liposils developed in this study could be an effective alternative to Taxol® and PTX liposomes.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Paclitaxel/chemistry , Silicon Dioxide/chemistry , Amines/administration & dosage , Amines/chemistry , Amines/pharmacokinetics , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacokinetics , Cell Line, Tumor , Cell Survival/drug effects , Cholesterol/administration & dosage , Cholesterol/chemistry , Cholesterol/pharmacokinetics , Drug Liberation , Drug Stability , Erythrocytes/drug effects , Hemolysis/drug effects , Humans , Liposomes , Male , Melanoma, Experimental , Mice , Paclitaxel/administration & dosage , Paclitaxel/pharmacokinetics , Phosphatidylcholines/administration & dosage , Phosphatidylcholines/chemistry , Phosphatidylcholines/pharmacokinetics , Rats, Sprague-Dawley , Silicon Dioxide/administration & dosage , Silicon Dioxide/pharmacokineticsABSTRACT
The present research work was aimed at developing solid lipid nanoparticle (SLN)-based formulation of budesonide (BDS) for nasal delivery. Melt emulsification method was chosen for fabrication of BDS-SLN using ultrasound dispersion and hot high-pressure homogenization techniques. The Compritol888 ATO was chosen as the lipid component for SLN formulation due to highest solubility for BDS. Different surfactants were screened and it was found that combination of Tween 80 and plurol oleique has shown desired particle size with improved stability and entrapment efficiency. The optimized SLN composition had a particle size of 185.2 nm with polydispersibility index of 0.387. Entrapment efficiency of the SLN composition was observed to be 61 %. Further, the optimized SLN dispersion was formulated into nasal spray. In vitro permeation study was carried out using Ovis aries (Indian sheep) nasal mucosa and it was observed that the permeability of BDS nasal spray of SLN was increased significantly by 3.4-fold as compared to the plain BDS and 1.8-fold as compared to the marketed nasal formulation. Thus, SLN-based nasal drug delivery was observed to be a promising approach for improving the bioavailability of hydrophobic drugs.
