Dual Activity of Hydroxypropyl-ß-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol.

Carvedilol (CAR) is a non-selective α and ß blocker categorized as class II drug with low water solubility. Several recent studies have investigated ways to overcome this problem. The aim of the present study was to combine two of these methods: the inclusion complex using hydroxypropyl-ß-cyclodextrin (HPßCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and the stability of CAR. Kneading method was used to prepare CAR-HPßCD inclusion complex (KD). The action of different carriers separately and in combination on Carvedilol solubility was investigated in three series. CAR-carrier and KD-carrier solid dispersions were prepared by solvent evaporation method. In vitro dissolution test was conducted in three different media: double-distilled water (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions between CAR, HPßCD, and different carriers were explored by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and PBS, respectively. DSC and XRD analyses indicated an improved degree of transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous state. This study provides a new successful combination of two polymers with the dual action of HPßCD and PLX/PVP on water solubility and bioavailability of CAR.

Cancer-related micropeptides encoded by ncRNAs: Promising drug targets and prognostic biomarkers.

An exciting emerging topic in the noncoding RNA (ncRNA) field is the discovery of short peptides called micropeptides (≤100 amino acids), whose novel therapeutic opportunities remain under-explored. Micropeptides have been suggested to play essential regulatory roles in diverse species of physiological and pathological processes. Genomics studies have revealed that these micropeptides are encoded by small open reading frames (sORFs) concealed in misannotated ncRNAs, generally lncRNAs (long noncoding RNAs) and circRNAs (circular RNAs). These ncRNA-encoded micropeptides have been shown to contribute to tumorigenesis but little is known about their pathological mechanism because of challenges in translated sORF identification techniques. Here, we review the best-validated micropeptides involved in the progression of human tumors and discuss their therapeutic and/or prognostic potential, at the same time, we also give our own suggestions on the concept of potential-coding RNA and micropeptides.

Comparative study on stabilizing ability of food protein, non-ionic surfactant and anionic surfactant on BCS type II drug carvedilol loaded nanosuspension: Physicochemical and pharmacokinetic investigation.

Carvedilol (CAR) in its pure state has low aqueous solubility and extremely poor bioavailability which largely limit its clinical application. The aim of the study is to improve the dissolution rate and the bioavailability of CAR via preparing nanosuspensions with different stabilizers. Antisolvent precipitation-ultrasonication technique was used here. Attempts have been made to use food protein- Whey protein isolate (WPI) as a stabilizer in CAR loaded nanosuspension and also to compare its stabilizing potential with conventional nanosuspension stabilizers such as non-ionic linear copolymer-poloxamer 188 (PLX188) and anionic surfactant-sodium dodecyl sulfate (SDS). Optimized nanosuspensions showed narrow size distribution with particle size ranging from 275 to 640nm. Amorphous state of CAR nanocrystals which also improved the solubility by 16-, 25-, 55-fold accordingly was confirmed by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). From scanning electron microscopy (SEM), flaky shape of PLX188 and SDS nanosuspensions could be revealed but WPI nanosuspension was sphere-shaped. Up to 70% dissolution of loaded drug was observed within 15min in phosphate buffer (pH6.8). A pharmacokinetic study in rats indicated that both Cmax and AUC0-36 values of nanosuspensions were estimated to be 2-fold higher than those of reference, suggesting a significant increase in CAR bioavailability.