ABSTRACT
In this study, high surface area mesoporous silica foam with cellular pore morphology (MCF) was used for injectable delivery of paliperidone, an antipsychotic drug used in patients suffering from bipolar disorder. The aim was to enhance paliperidone solubility and simultaneously to prepare long active intractable microspheres. For this reason paliperidone was first loaded in MCF silica, and the whole system was further encapsulated into PLA and PLGA 75/25w/w copolymer in the form of microspheres. It was found that paliperidone, after its adsorption into MCF, was transformed in its amorphous state, thus leading to enhanced in vitro dissolution profile. Furthermore, incorporation of the drug-loaded MCF to polymeric microparticles (PLA and PLGA) prolonged the release time of paliperidone from 10 to 15days.
Subject(s)
Antipsychotic Agents/chemical synthesis , Microspheres , Paliperidone Palmitate/chemical synthesis , Polymers/chemical synthesis , Silicon Dioxide/chemical synthesis , Antipsychotic Agents/metabolism , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/metabolism , Drug Compounding/methods , Drug Liberation , Injections, Subcutaneous , Paliperidone Palmitate/metabolism , Poloxalene/chemical synthesis , Poloxalene/metabolism , Polymers/metabolism , Porosity , Silicon Dioxide/metabolism , X-Ray Diffraction/methodsABSTRACT
In this work, high surface area mesoporous silica (SBA-15) was loaded with paclitaxel (taxol, PTX) and was further entrapped into poly(lactic acid-co-glycolic acid) (PLGA) microparticles (MPs). A modified solvent evaporation-emulsion method was used in order to formulate the composite microparticles with sizes of 8-12µm. PTX loaded SBA-15 as well as the PLGA/PTX-SBA-15 composites were characterized in terms of their morphology, crystal structure and thermal properties. Drug content, loading efficiency, particle size and the in-vitro drug release kinetics of the PLGA/PTΧ-SBA-15 microspheres were also investigated. The in vitro release studies were carried out using Simulated Body Fluid (SBF) at 37°C revealing that the prepared formulations present higher dissolution rate than pure PTX and sustained pattern which is ideal for anticancer carriers. Modeling and data analysis of the in vitro drug release was also investigated. It was also shown that all microparticles have low cytotoxicity in HUVE cells. Finally, it was found that drug loaded microparticles are very effective in Human Cervical Adenocarcinoma (HeLa) cells.
Subject(s)
Antineoplastic Agents/chemistry , Lactic Acid/chemistry , Paclitaxel/chemistry , Polyglycolic Acid/chemistry , Silicon Dioxide/chemistry , Cell Line , Cell Line, Tumor , Chemistry, Pharmaceutical/methods , Drug Carriers/chemistry , Emulsions/chemistry , HeLa Cells , Human Umbilical Vein Endothelial Cells , Humans , Microspheres , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Solvents/chemistryABSTRACT
A series of seven fast-biodegrading aliphatic polyesters were prepared from 1,3-propanediol and aliphatic diacids with increasing number of methylene units (x). Melting points decreased from PPSu to PPAd and then increased again to PPAz and PPSeb. Crystallization rates and thermal stability increased steadily with increasing x. Glass transition temperatures decreased steadily to PPPim and subsequently increased. Enzymatic degradation of the polymers in the presence of a mixture of Rhizopus delemar and Pseudomonas cepacia lipases was much faster than that of poly(epsilon-caprolactone). All the polyester specimens were almost disintegrated within 36 h. PPSub exhibited the fastest enzymatic hydrolysis rates, PPAd and PPSuc the slowest.
