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Formononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes. Our data showed both groups improved FNT water solubility and oil-water partition coefficient. NMR, DSC, and SEM were performed to identify the interaction and the geometrical nature of complex. When compared, FNT-PIP-PC released more FNT in in vitro release and permeation through Caco-2 monolayer than FNT-PC and pure FNT. In vitro data was consistent with the in vivo pharmacokinetic profile that showed increased, Cmax and AUC(0-24) by 7.16 and 23.33-fold and 29.65 and 23.33-fold at 5 and 10 mg/kg in FNT-PIP-PC, compared to pure FNT. Additionally, co-treatment of PIP and FNT improved in vitro pharmacological action in dexamethasone-induced osteoporosis. Thus, our study showed addition of PIP in FNT-PC further increases FNT water solubility and protects it from phase II metabolism, leading to enhanced bioavailability with improved pharmacological activity. [ABSTRACT FROM AUTHOR]

Herbal slimming products (HSPs) contain multiple herbs used in weight loss. Phytoconstituents of several plant extracts show the inhibitory effects on the drug-metabolizing enzymes causing interaction when taken with other drugs. Atorvastatin (ATS) is used in the treatment of hyperlipidemia. This study aimed to investigate the effect of HSPs on the pharmacokinetics and pharmacodynamics of ATS. ATS (10 mg/Kg) was administered alone or in combination with HSP1 (200 mg/Kg)/HSP2 (165 mg/Kg) orally in the SD rats for pharmacokinetics study. Hyperlipidemia was induced in Golden Syrian Hamster by feeding HFD (60% kcal). Furthermore, biochemical levels in serum, ROS, gene expression and lipid accumulation levels were examined in hamster liver tissue. HSPs have significantly enhanced the permeability and inhibited the metabolism of ATS by inhibiting the CYP3A4 isoenzyme confirmed by in vitro assay. Co-administration of HSPs with ATS enhanced the relative bioavailability of ATS.Concomitant administration of HSPs with ATS has significantly reduced the fat content, inflammatory cytokines, TG, VLDL, LDL levels, tissue MDA level, HMGCR and SREBP1c mRNA expression levels, lipid accumulation as well as collagen content and has increased the serum HDL level as well as tissue SOD, CAT, GHS and mRNA expression levels of LXRa and CYP7A1. The aforementioned outcomes indicated that coadministration of HSPs with ATS may lead to herb-drug interaction. Therefore, precaution should be taken and dose adjustment is required when administered simultaneously. [ABSTRACT FROM AUTHOR]

Abiraterone acetate (ABRTA) is clinically beneficial in management of metastatic castration-resistant prostate cancer (PC-3). With highlighted low solubility and permeability, orally hampered treatment of ABRTA necessitate high dose to achieve therapeutic efficacy. To triumph these challenges, we aimed to develop intestinal lymphatic transport facilitating lipid-based delivery to enhance bioavailability. ABRTA-containing self-nano emulsified drug delivery (ABRTA-SNEDDS) was statistically optimized by D-optimal design using design expert. Optimized formulation was characterized for particle size, thermodynamic stability, in vitro release, in vivo bioavailability, intestinal lymphatic transport, in vitro cytotoxic effect, anti-metastatic activity, and apoptosis study. Moreover, hemolysis and histopathology studies have been performed to assess pre-clinical safety. Nano-sized particles and successful saturated drug loading were obtained for optimized formulation. In vitro release upto 98.61 ± 3.20% reveal effective release of formulation at intestinal pH 6.8. ABRTA-SNEDDS formulation shows enhanced in vivo exposure of Abiraterone (2.5-fold) than ABRTA suspension in Sprague–Dawley rats. In vitro efficacy in PC-3 cell line indicates 3.69-fold higher therapeutic potential of nano drug delivery system. Hemolysis and histopathology study indicates no significant toxicities to red blood cells and tissues, respectively. Apparently, an opportunistic strategy to increasing bioavailability of ABRTA via intestinal lymphatic transport will create a viable platform in rapidly evolving chemotherapy. Enhanced translational utility of delivery was also supported through in vitro therapeutic efficacy and safety assessments. Abiraterone acetate is a prostate cancer drug, impeded with low bioavailability. ABRTA loaded in self nano emulsifying drug delivery enhanced its bioavailability. Intestinal lymphatic transport played role in enhanced bioavailability of ABRTA. ABRTA-SNEDDS enhanced in vitro cytotoxic activity of ABRTA. ABRTA-SNEDDS found safe in preclinical safety evaluations [ABSTRACT FROM AUTHOR]

'One drug- one target' to 'multiple drug- multiple targets' paradigm shifted to produce combination therapies, have found great outcomes to overcome multiple drug resistance (MDR). MDR is a significant barrier to the delivery of taxane-based anticancer medicines such as docetaxel, paclitaxel, and cabazitaxel. Due to MDR induced by drug efflux transporters, clinical application of these medications is impeded. To date, nanoformulations such as liposomes, micelles, polymeric nanoparticles, and gold nanoparticles have been investigated to deliver taxanes alone and in combination to reverse drug resistance. Despite the fact that various groups have already looked into taxane nano formulations in the literature, there isn't much in the way of polypharmacology and advanced nanoformulations with a focus on MDR. In this overview, we briefly covered the insights regarding MDR, difficulties related to current pharmaceutical products of taxanes, combination therapies of taxanes to combat MDR, all of which can be used to delve into cancer treatment. [ABSTRACT FROM AUTHOR]

Trans-Resveratrol (T-RES) is a compound with wide therapeutic applications that shows low bioavailability and distribution across blood-brain barrier. The purpose of our study was to develop T-RES loaded mixed micelle (T-RES-MM) for its enhanced systemic availability and targeting to the brain. T-RES-MMs were formulated using Pluronic F-127 (PF-127) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) by using film hydration process. Formulations were characterized for size of particles, zeta potential, drug efficiency of entrapment, drug loading, and hemolytic study. Further in vivo pharmacokinetic and brain distribution study carried out in Sprague Dawley rats. The nano ranged size for drug-loaded mixed micelles was 21.55 ± 2.15 nm for optimized formulation with PF-127:TPGS (4:1). Formulation with maximum drug loading and entrapment efficiency of 8.4 ± 0.37% and 94.37 ± 1.01% respectively were further used for in vivo study. Percent hemolysis by micelles at all concentrations indicates the biocompatibility and safety for administration by i.v. route. The AUC0-t for T-RES-MM was 460.98 ± 158.99 h*ng/ml while for T-RES it was 276.27 ± 174.05 h*ng/ml. Drug targeting index suggests successful targeting of T-RES to the brain. Overall findings conclude in prepared T-RES-MM exhibit superiority of formulation as compared to T-RES solution. [ABSTRACT FROM AUTHOR]