Novel Biodegradable Polyesters. Synthesis and Application as Drug Carriers for the Preparation of Raloxifene HCl Loaded Nanoparticles

Abstract

Raloxifene HCl is a drug with poor bioavailability and poor water solubility. Furthermore nο pharmaceutically acceptable organic solvent has been reported before to dilute the drug. It was observed that Raloxifene HCl can be diluted in a solvent mixture of acetone/water or ethanol/water. The aim of this study was to use biodegradable polymers in order to prepare Raloxifene HCl nanoparticles. For this purpose a series of novel biodegradable poly(ethylene succinate-co-propylene adipate) P(ESu-co-PAd) polyesters were synthesized following the polycondensation method and further, poly(ethylene succinate) (PESu) and poly(propylene adipate) (PPAd) were used. The prepared polyesters were characterized by intrinsic viscosity measurements, end group analysis, enzymatic hydrolysis, Nuclear Magnetic Resonance Spectroscopy (1Η-NMR and 13C-NMR) and Wide-angle X-ray Diffractometry (WAXD). The drug nanoparticles have been prepared by a variation of the co-precipitation method and were studied by Wide-angle X-ray Diffractometry (WAXD), FTIR spectrometry, light scattering size distribution, Scanning Electron Microscopy (SEM) and release behavior measurements. The interactions between the polymers and the drug seem to be limited, so the drug occurs in crystalline form in all nanoparticles. The size of the nanoparticles seems to be in the range of 150-350 nm, depending on the polymer that was used. The drug release depends on the melting point and degree of crystallinity of the polyesters used. An initial high release rate was recorded followed by very slow rates of controlled release.

Evaluating the effects of crystallinity in new biocompatible polyester nanocarriers on drug release behavior

“…Use of similar aliphatic polyesters derived from 1,3 propanediol and carboxylic acids as nanocarriers has been previously studied and reported. [23][24][25] These polyesters have been used previously for the preparation of a solid dispersion by melt mixing, while some of their copolymers have been effective for nanoencapsulation and sustained release of nimodipine. 25 Figure 3 demonstrates that all the polyesters studied had low toxicity in human umbilical vein endothelial cells, with appreciable …”

Synthesis of biocompatible poly(ε-caprolactone)-block-poly(propylene adipate) copolymers appropriate for drug nanoencapsulation in the form of core-shell nanoparticles

“…32,33 Based on polymer toxicity on HUVEC, the biocompatibility of the studied copolyesters was comparable to the biocompatibility of PLA, which is also widely used as drug carrier. 34 The new aliphatic polyesters reported here have a potential for drug delivery applications, by analogy to PCL or PLA.…”

Development, validation, and pharmacokinetic application of liquid chromatographic method for estimation of raloxifene hydrochloride in rabbit plasma

“…The reported LC methods for analysis of RLX in plasma samples are less sensitive; hence, it was decided to develop a rapid, sensitive, and accurate method for estimation of RLX in plasma samples. Further, reports were found on the development of novel delivery systems of RLX using nanocarrier techniques for improving solubility, bioavailability, and distribution of the drug in effective treatment of post-menopausal osteoporosis [17]. Such research endeavors need a sensitive, simple, rapid, and cost-effective bioanalytical method for quantification of RLX in the pharmacokinetic evaluation of developed novel drug delivery systems in suitable animal models.…”