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Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (ß-CD) and sulfobutyl ether7 ß-CD (SBE7 ß-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 ß-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5-348.4 nm, with polydispersity index (PDI) ranging from 0.302-0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75-88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

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Docetaxel (DTX) is a chemotherapeutic drug with poor hydrophilicity and permeability. Its lipophilic properties decrease its absorption in systemic circulation which hinders its therapeutic efficacy & safety. Cyclodextrins (CDs) with their unique structural properties enhance solubility of chemotherapeutic drugs. The study was designed to formulate docetaxel-cyclodextrins inclusion complexes for enhancement of solubility with sulfobutyl ether ß-cyclodextrin (SBE7-ß-CD), hydroxypropyl ß-cyclodextrin (HP-ß-CD) and ß-cyclodextrin (ß-CD). Further, by using ionic gelation method polymeric nanoparticles of docetaxel-cyclodextrins were prepared with sodium tri poly phosphate (STPP) and chitosan (CS). Optimization is performed by varying CS and STPP mass ratios. Nanoparticles were analyzed for their physicochemical properties, drug-excipient compatibility, thermal stability and oral toxicity. CDs enhanced the solubility of DTX. Nanoparticles were found within 144.8 ± 65.19 - 372.0 ± 126.9 nm diameters with polydispersity ranging 0.117-0.375. The particles were found round & circular in shape with smooth and non-porous surface. Increased quantity of drug release was observed from DTX-CDs loaded nanoparticles than pure drug loaded nanoparticles. Oral toxicity in rabbits revealed biochemical, histopathological profile with no toxic effect on cellular structure of animals.

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BACKGROUND: Epalrestat (EPL) is a carboxylic acid derivative with poor aqueous solubility and its pharmacokinetic features are not fully defined. PURPOSE: Current research aimed to fabricate inclusion complexation of EPL with SBE7 ß-CD (IC) and EPL/SBE7 ß-CD CS NPs (NP). METHODS: EPL was complexed with SBE7 ß-CD using the co-precipitation method, and the prepared complex was fabricated into nanoparticles using the ionic gelation method. The prepared formulations were characterized for particle size analysis, surface morphology, and in vitro dissolution study. The % inhibition of EPL against α-glucosidase enzyme was also conducted to check the drug's antidiabetic activity. Finally, an in vivo pharmacokinetic investigation was carried out to determine the concentration of EPL in rabbit plasma of the prepared formulation. In vivo pharmacokinetic studies were conducted by giving a single dose of pure EPL, IC, and NP. RESULTS: The size of NP was found to be 241.5 nm with PDI 0.363 and zeta potential of +31.8 mV. The surface of the prepared NP was non-porous, smooth and spherical when compared with pure EPL, SBE7 ß-CD and IC. The cumulative drug release (%) from IC and NP was 73% and 88%, respectively, as compared to pure drug (25%). The % inhibition results for in vitro α-glucosidase was reported to be 74.1% and the predicted binding energy for in silico molecular docking was calculated to be -6.6 kcal/mol. The calculated Cmax values for EPL, IC and NP were 4.75±3.64, 66.91±7.58 and 84.27±6.91 µg/mL, respectively. The elimination half-life of EPL was 4 h and reduced to 2 h for IC and NP. The AUC0-α for EPL, IC and NP were 191.5±164.63, 1054.23±161.77 and 1072.5±159.54 µg/mL*h, respectively. CONCLUSION: Taking these parameters into consideration it can be concluded that IC and NP have prospective applications for greatly improved delivery and regulatedt release of poorly water soluble drugs, potentially leading to increase therapeutic efficacy and fewer side effects.

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This study aimed to prepare novel colon targeted celecoxib-ß-cyclodextrin (CXB-ß-CD) inclusion complex loaded eudragit S 100 (ES100) microparticles for chronotherapy of rheumatoid arthritis (RA) which is an innovative approach, never reported before, for the fabrication of CXB-ß-CD complex in the form of microparticles and its colon targeting. CXB was complexed with ß-cyclodextrin by kneading technique and we evaluated the effect of ß-CD on saturation solubility of CXB. Microparticles were developed by oil-in-oil emulsion solvent evaporation technique and formulation variables (polymer conc, surfactant conc and stirring speed) were optimized by using three-factor three-level Box-Behnken design (BBD). SEM imaging revealed smooth, uniform and spherical shape microparticles. There was 7.3 fold increases in saturation solubility of CXB-ß-CD inclusion complex in distilled water as compared to pure CXB. Particle size was in the range of 50.42 µm to 238.38 µm with entrapment efficiency of 68.47% to 91.65%. Biphasic drug release pattern was found i.e initially delayed release in stomach and small intestine followed by fast release at colonic pH. Response variable results achieved from optimized formulation were very close to the response values suggested by BBD signifying the actual reliability and robustness of BBD in the fabrication of colon targeted CXB-ß-CD microparticles. The comparison of CXB-ß-CD optimized formulation with optimized formulation containing pure CXB showed increase in drug release due to enhancement of water solubility of CXB-ß-CD inclusion complex. So, it can be concluded that CXB-ß-CD loaded ES100 microparticles can be successfully fabricated with enhanced solubility for the chronotherapy of rheumatoid arthritis.

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The history of cancer chemotherapy is as old as cancer itself. With the increase in the complexities of cancer and the development of resistance towards existing anticancer agents, increased attention is now being paid to the advancement of chemotherapy. Some chemotherapeutic agents were discovered by accident or trial-and-error methods while others were found to be useful for neoplasia when they were being evaluated for some other purpose. Broadly, these agents have been classified as alkylating agents, antimetabolites, platinum compounds, antitumor antibiotics and natural products. Hormones and compounds interfering with hormone metabolism are widely used in cancer treatment, besides monoclonal antibodies and small molecules targeting angiogenesis. In this review an attempt is made to discuss the major breakthroughs that have shaped the course of cancer chemotherapy, helping to decrease the mortality as well as lessen the suffering of patients.

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