ABSTRACT
In the preparation of nanoparticles (NPs) by the nanoprecipitation method, emulsifiers play a key role for NPs' characteristics. The present study aimed to investigate the combined emulsifier effect on ibuprofen loaded poly(lactic-co-glycolic acid) (PLGA) NPs' characteristics and anticancer activity. Ibuprofen loaded PLGA NPs were prepared by nanoprecipitation using different concentrations of PVA (poly(vinyl alcohol)) or PVA-TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) combination as emulsifier. It was found that encapsulation efficiencies of NPs varied between 17.9 and 41.9 % and the highest encapsulation efficiency was obtained with 0.5% PVA + 0.1% TPGS (coded as PLGA PVA/TPGS NPs). PLGA PVA/TPGS NPs were characterized and compared with PLGA PVA NPs, which was obtained by 0.5% PVA alone. Polydispersity index of PLGA PVA/TPGS and PLGA PVA NPs were found to be 0.08 and 0.15, respectively. Incorporation of TPGS with PVA slightly decreased the initial ibuprofen release. Transmission electron microscopy analyses demonstrated a nearly uniform particle size distribution and spherical particle shape of the PLGA PVA/TPGS NPs. Additionally, PLGA PVA/TPGS NPs were significantly more cytotoxic than PLGA PVA NPs on the MCF-7 (human breast adenocarcinoma cells) and Caco-2 (human epithelial colorectal adenocarcinoma) cells (p<0.05). Also PLGA PVA/TPGS NPs were not cytotoxic on normal cells (L929, mouse healthy fibroblast cells) (p>0.05). In conclusion, these results indicated that using a combination of TPGS and PVA as an emulsifier in nanoprecipitation could be a promising approach for preparing ibuprofen loaded PLGA NPs because of their improved characteristics and anticancer activity.
Subject(s)
Antineoplastic Agents/administration & dosage , Emulsifying Agents/chemistry , Ibuprofen/administration & dosage , Nanoparticles , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Animals , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Caco-2 Cells , Chemistry, Pharmaceutical/methods , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Drug Liberation , Female , Humans , Ibuprofen/pharmacology , Lactic Acid/chemistry , MCF-7 Cells , Mice , Microscopy, Electron, Transmission/methods , Particle Size , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Polyvinyl Alcohol/chemistry , Vitamin E/chemistryABSTRACT
Alpha-phenyl-n-tert-butyl nitrone (PBN) shows its major effect by scavenging free radicals formed in the ischemia and it has the ability to penetrate through the blood brain barrier easily. The in vivo stability of PBN is very low and when administered systemically, it has a mean plasma half life of about three hours. Therefore, formulations which are able to prolong the plasma residence time of PBN are of major interest, because oxygen radicals are usually continuously formed under pathological conditions. In this study, PBN, a nitrone compound having neuroprotective properties, was encapsulated in chitosan (CS) and chitosan-poly(ethylene glycol) (CS-PEG) nanoparticles for treatment of diseases such as stroke, in which sustained free radical production is reported. The nanoparticles were characterized through particle size determination, zeta potential, encapsulation efficiency, surface morphology determinations and in vitro release studies. The surface morphologies were evaluated by transmission electron microscopy (TEM) and nanoparticles having spherical shapes were characterized. The particle size distribution was between approximately 97 nm and approximately 322 nm; and the zeta potentials varied between approximately 9 mV and approximately 33 mV. Size of the nanoparticle formulations was important for the release of PBN from nanoparticles. The quantitative determination of PBN has been evaluated by a validated analytical HPLC method. The presented chitosan-based nanotechnology opens new perspectives for testing antioxidant activity in vivo.
Subject(s)
Cyclic N-Oxides/administration & dosage , Cyclic N-Oxides/chemistry , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/chemistry , Chemistry, Pharmaceutical , Chitosan , Drug Compounding , Electrochemistry , Excipients , Nanoparticles , Particle Size , Polyethylene Glycols/chemistryABSTRACT
Many high-grade embryos selected for transfer according to their morphological evaluation were detected to have chromosomal abnormalities after aneuploidy screening for infertility by preimplantation genetic diagnosis (PGD). The aim of this study was to detect if there is any correlation between embryo quality and genetic status. The chromosomal status of the day three embryos was studied by multicolour fluorescence in-situ hybridization for chromosomes 13, 18, 21, X and Y. PGD was performed on 132 patients for 1107 embryos. The correlation between embryo quality and aneuploidy was analysed. The analysis showed that a large proportion of normal embryos (50.7%, n = 280) were grade I. In addition, a considerably high proportion of aneuploid embryos (36.1%, n = 83) were evaluated as grade I. There was a significant relationship between PGD results and embryo grades (P = 0.001). Of the 69 polyploid embryos, 21.7% were grade I and 37.8% were grade II. Of the 83 haploid embryos, 27.8% were grade I and 34.9% were grade II. Euploidy was positively related to morphological grade of embryo (P = 0.001). It was also possible for chromosomally abnormal embryos to have a good developmental potential, and they could be selected for embryo transfer unless the PGD procedure was applied.
