Dimensional changes, gel layer evolution and drug release studies in hydrophilic matrices loaded with drugs of different solubility

The objective of this investigation was to explore the effects of drug solubility on the evolution of matrix dimensions and gel layer's during drug release and investigate the relationship between these effects and the mechanism and the rate of drug release. Two hydrophilic swellable polymers Polyox (POL) and cross-linked Carbopol (CARB) were employed as carriers. Caffeine (CAF) and theophylline (THE), two drugs having similar chemical structure but different aqueous solubility, were used as model drugs. Both drug and polymer characteristics were found to influence the dimensional changes of matrices and the development of the gel layer formed around the glassy core. The dimensional expansion in CAF matrices was always more pronounced than the THE matrices. Also the CARB matrices demonstrated greater maximum expansion and lower drug release than the POL matrices, due to a smaller degree of erosion of CARB. The dimensions of CARB/CAF matrices, unlike all the other matrices studied, exhibited a biphasic increase at early times, which was attributed to the cross-linked structure of CARB and the high solubility of CAF. With both polymers, a thinner gel layer was developed in the matrices containing the less soluble THE compared to the CAF matrices. The thickness of the gel layer increased continuously with time in the CAF matrices whereas it increased initially and after reaching a maximum started to decrease in THE matrices. All formulations except those of CARB/THE exhibited burst release, which depended on drug and polymer characteristics. The gel layer thickness and erosion rate appeared to determine the rate of drug release from the CARB and POL formulations. The results clearly indicate that for these matrices gel thickness and fluctuation of gel thickness affect the release rate/h of drug proportionally. Analysis of the release kinetics indicated that CAF was released mainly through diffusion whereas, THE was released mainly through matrix erosion. © 2007 Elsevier B.V. All rights reserved

Simultaneous optimization of cisplatin-loaded PLGA-mPEG nanoparticles with regard to their size and drug encapsulation

A central composite experimental design was applied to investigate the effect of five preparative variables on the size and cisplatin encapsulation efficiency of poly(lactide-co-glycolide)-methoxy poly(ethylene glycol) (PLGA-mPEG) nanoparticles. The nanoparticles were prepared by a nano-precipitation process and were characterized with regard to their morphology by scanning electron microscopy, their size by photon correlation spectroscopy and their drug content by atomic absorption spectroscopy respectively. The preparative variables investigated were: solids concentration, aqueous to organic phase volume ratio, temperature, rate of organic phase addition in aqueous phase and agitation. The nanoparticles prepared in this study appeared to be spherical and rather homogeneous in size under the scanning electron microscope. The size and the drug encapsulation of the prepared nanoparticles ranged between 90-180 nm and 0%-40%, respectively. The fitted model could adequately describe the experimental data. The statistical analysis showed that all preparative variables studied, except temperature, affected significantly both the size and the drug loading of nanoparticles. The size was most affected by the agitation whereas the loading was most affected by the phase ratio. Significant interactions between the preparative variables were also observed. The "desirability function" approach was applied to simultaneously optimize the nanoparticles with regard to their size and cisplatin encapsulation. The predictive power of the applied model was more satisfactory in the case of nanoparticles size than with cisplatin encapsulation efficiency. It appears to be feasible to select optimum conditions for the preparation of PLGA-mPEG nanoparticles of cisplatin based on a central composite design and the "desirability function" optimization approach. © 2008 Bentham Science Publishers Ltd

Synthesis and angiogenetic activity in the chick chorioallantoic membrane model of thymosin beta-15

Thymosin beta-15 (Tβ15), a 44 amino acid peptide (MW=5173) localized in human prostate and breast cancer tissues was successfully synthesized in multigram quantities using Fmoc solid-phase peptide synthesis. The synthesized product was shown to have the right structure by ESI and MALDI mass spectral techniques and amino acid analysis. Relatively high yield was achieved, which might be due to enhanced acid stability of the p-cyanotrityl resin used. The effect of the synthesized Tβ15 on the angiogenesis process was investigated using the chick chorioallantoic membrane (CAM) in vivo model. At concentrations above 1μg/10μl per disc, Tβ15 exhibited a positive effect on angiogenesis, comparable to the effect of the intense angiogenetic factor phorbol 12-myristate 13-acetate at a standard concentration of 0.1μg/10μl per disc. The results of this study contribute to the further elucidation of the biological regulatory role of thymosin peptides and provide helpful information in the investigation of their possible therapeutic potential. © 2002 Elsevier Science Inc. All rights reserved

Synthesis of folate- pegylated polyester nanoparticles encapsulating ixabepilone for targeting folate receptor overexpressing breast cancer cells

Abstract: The aim of this study was the preparation of novel polyester nanoparticles based on folic acid (FA)–functionalized poly(ethylene glycol)–poly(propylene succinate) (PEG–PPSu) copolymer and loaded with the new anticancer drug ixabepilone (IXA). These nanoparticles may serve as a more selective (targeted) treatment of breast cancer tumors overexpressing the folate receptor. The synthesized materials were characterized by 1H-NMR, FTIR, XRD and DSC. The nanoparticles were prepared by a double emulsification and solvent evaporation method and characterized with regard to their morphology by scanning electron microscopy, drug loading with HPLC–UV and size by dynamic light scattering. An average size of 195 nm and satisfactory drug loading efficiency (3.5 %) were observed. XRD data indicated that IXA was incorporated into nanoparticles in amorphous form. The nanoparticles exhibited sustained drug release properties in vitro. Based on in vitro cytotoxicity studies, the blank FA–PEG–PPSu nanoparticles were found to be non-toxic to the cells. Fluorescent nanoparticles were prepared by conjugating Rhodanine B to PEG–PPSu, and live cell, fluorescence, confocal microscopy was applied in order to demonstrate the ability of FA–PEG–PPSu nanoparticles to enter into human breast cancer cells expressing the folate receptor. Graphical Abstract: [Figure not available: see fulltext.] © 2015, Springer Science+Business Media New York