Characteristics and anticancer properties of Sunitinib malate-loaded poly-lactic-co-glycolic acid nanoparticles against human colon cancer HT-29 cells lines

Purpose: To develop poly-lactic-co-glycolic acid (PLGA) -based nanoparticles (NPs) for the delivery of sunitinib malate (STM) to colon cancer cells.Methods: Three different formulations (F1 – F3) were developed by nano-precipitation technique using various concentrations of PLGA. The NPs were evaluated for particle size, polydispersity index, zeta potential, drug entrapment, and drug loading, using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Furthermore, in vitro drug release and anticancer studies were carried out on the formulations.Results: Among the three NPs, optimized NP (F3) of STM was chosen for in vitro anti-cancer study against H-29 human colon cancer cells lines based on its particle size (132.9 nm), PDI (0.115), zeta potential (-38.12 mV), entrapment efficiency (52.42 %), drug loading (5.24 %), and drug release (91.26 % in 48 h). A significant anti-cancer activity of the optimized NPs was observed, relative to free STM.Conclusion: These findings suggest that STM-loaded NPs possess significant anti-cancer activity against human colon cancer HT-29 cells lines.Keywords: Sunitinib malate, Poly-lactic-co-glycolic acid, Nanoparticles, Colon cance

Design, statistical optimization, and characterization of Esculin-loaded transliposome nanogel for topical delivery: In-vitro, ex vivo study and dermatokinetic evaluation

The purpose of this study was to prepare and optimise an Esculin-loaded transliposome (ECL-TL) for the dermal administration of ECL for skin cancer treatment. The ECL-TL formulation effectively produced closed lamellar vesicles with in-vitro drug release of 81.28 ± 2.82 % and ex-vivo penetration studies showed that had a 2.2-part intensified permeability compared to the conventional preparation. The CLSM data of skin visibly displayed intense permeation of ECL-TL formulated with rhodamine B, equating to the rhodamine B hydroalcoholic solution. The dermatokinetic study suggested that TLs enhance the permeability of the delivery system when topically applied. According to the data, the developed ECL-TL could be an effective drug nano-carrier for the dermal delivery of ECL in treating skin cancer

Preparation, Evaluation and Bioavailability Studies of Eudragit Coated PLGA Nanoparticles for Sustained Release of Eluxadoline for the Treatment of Irritable Bowel Syndrome

Eluxadoline is a newly approved orally administered drug used for the treatment of Irritable Bowel Syndrome with Diarrhea. It is reported as a poorly water-soluble drug due to which its dissolution rate and oral bioavailability are very poor. In this work, various plain PLGA nanoparticles (NPs) (F1–F4) were prepared and optimized based on particle size, PDI, zeta potential and percent drug entrapment efficiency (EE). The developed plain NPs (F1–F4) showed average particle size ranging from 260.19 to 279.76 nm with smooth surface and EE of 17.83–56.29%. The optimized plain NPs (F3) had particle size of 273.76 ± 7.25 nm with a low PDI value 0.327, zeta potential - 30.63 ± 2.47 mV and % EE of 56.29 ± 2.56%. The optimized F3 NPs was further submitted for enteric coating using Eudragit S100 polymer and evaluated in terms of particles characterization, in vitro release and pharmacokinetic studies in rats. The bioavailability of plain and coated nanaoparticles were enhanced by 6.8- and 18.5-fold, respectively, compared to normal suspension. These results revealed that the developed coated NPs could be used for its oral delivery for an effective treatment of Irritable Bowel Syndrome with Diarrhea

Application of CO2 Supercritical Fluid to Optimize the Solubility of Oxaprozin: Development of Novel Machine Learning Predictive Models

Over the last years, extensive motivation has emerged towards the application of supercritical carbon dioxide (SCCO2) for particle engineering. SCCO2 has great potential for application as a green and eco-friendly technique to reach small crystalline particles with narrow particle size distribution. In this paper, an artificial intelligence (AI) method has been used as an efficient and versatile tool to predict and consequently optimize the solubility of oxaprozin in SCCO2 systems. Three learning methods, including multi-layer perceptron (MLP), Kriging or Gaussian process regression (GPR), and k-nearest neighbors (KNN) are selected to make models on the tiny dataset. The dataset includes 32 data points with two input parameters (temperature and pressure) and one output (solubility). The optimized models were tested with standard metrics. MLP, GPR, and KNN have error rates of 2.079 × 10−8, 2.173 × 10−9, and 1.372 × 10−8, respectively, using MSE metrics. Additionally, in terms of R-squared, they have scores of 0.868, 0.997, and 0.999, respectively. The optimal inputs are the same as the maximum possible values and are paired with a solubility of 1.26 × 10−3 as an output

TEMPERATURE DEPENDENT SOLUBILITY STUDIES OF BRIGATINIB IN SOME PURE SOLVENTS USEFUL IN DOSAGE FORM DEVELOPMENT

In the current study, thermodynamic dissolution of brigatinib in six pure solvents namely, water, ethanol, isopropyl myristate (IPM), poly(ethylene glycol)-400 (PEG-400), dichloromethane (DCM) and ethyl acetate (EA) at (298.2-323.2K) temperature and 0.1 MPa atm. pressure were carried out using flask shaking technique.The mole-fraction solubility of brigatinib was obtainedgreatest in IPM (6.09 x 10-2) and least in water (3.12 x 10-6) at298.2 K.Experimentally obtained solubilities values of brigatinib were regressed using adapted Apelblat equation with root mean square deviations in the range of 1.91 to 4.67 in all solvents and similar trends were observed with increased the temperature. The solubility data generated in this investigation could be helpful for investigator for analysis/dosage form development of brigatinib

Mefenamic acid taste-masked oral disintegrating tablets with enhanced solubility via molecular interaction produced by hot melt extrusion technology

The objective of this study was to enhance the solubility as well as to mask the intensely bitter taste of the poorly soluble drug, Mefenamic acid (MA). The taste masking and solubility of the drug was improved by using Eudragit® E PO in different ratios via hot melt extrusion (HME), solid dispersion technology. Differential scanning calorimetry (DSC) studies demonstrated that MA and E PO were completely miscible up to 40% drug loads. Powder X-ray diffraction analysis indicated that MA was converted to its amorphous phase in all of the formulations. Additionally, FT-IR analysis indicated hydrogen bonding between the drug and the carrier up to 25% of drug loading. SEM images indicated aggregation of MA at over 30% of drug loading. Based on the FT-IR, SEM and dissolution results for the extrudates, two optimized formulations (20% and 25% drug loads) were selected to formulate the orally disintegrating tablets (ODTs). ODTs were successfully prepared with excellent friability and rapid disintegration time in addition to having the desired taste-masking effect. All of the extruded formulations and the ODTs were found to be physically and chemically stable over a period of 6 months at 40 °C/75% RH and 12 months at 25 °C/60% RH, respectively