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

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

Solanum pseudocapsicum vs Capsicum annum; comparative phenolics profiling using green ultrasonic extraction and UHPLC analysis

Background: Solanum pseudocapsicum (PC) and Capsicum annum (CA) belongs to the family of Solanaceae. CA have been reported a rich source of phenolics whereas, the phenolics content of GA (gallic acid), SC (scopoletin), RA (rosmarinic acid), and RV (resveratrol) are yet to be reported for the PC-fruit. This study comparatively evaluates the phenolics profile for different parts (seeds and skin) and colors (green and red) of the PC- and CA-fruits using the green solvents of ethanol (ET), acetone (AC), water (H2O), and different combinations of these solvents. Methodology: Ultrasonics extraction (US) and UHPLC analysis were employed for phenolics evaluation. Results: The USMD (method development) revealed the highest extract yield of 62 mg/100 mg for the PC-skin in ET:AC (70:30) solvent whereas, more phenolics (ppm) were observed for PC-seeds in ET:AC (50:50) solvent, particularly the SC (29.46) and GA (16.92). The UHPLCMDMV exhibited significant accuracies (100.70–114.14 %) with r2-values (0.9993–0.9997) in the linearity range of 1–200 ppm. The USMV (method validation) in PC- and CA-fruit parts and colors revealed more extract yields for the red skin part of the PC- (180.5 mg) and CA-fruit (126.2 mg). The phenolics were seen more in the green seeds of the PC-fruit (ppm); SC (276), GA (147.36), RV (28.54), and RA (23.87) followed by the green PC-skin, and red/green CA-seeds. The statistical models of mean differences, ANOVA, and Pearson’s correlation showed significant differences for the PC-fruit parts (seeds and skin) and colors (red and green) vs extract yield and phenolics content (P = 0.05). Conclusion: PC-and CA-fruits were successfully evaluated where the seeds for the green fruits exhibited more phenolics amount

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

Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid.

The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs

Efficacy of SPG-ODN 1826 Nanovehicles in Inducing M1 Phenotype through TLR-9 Activation in Murine Alveolar J774A.1 Cells: Plausible Nano-Immunotherapy for Lung Carcinoma

Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family mediates an important role in recognizing and mounting an immune response against intruding microbes. TLR-9 is a member of the intracellular TLR family, which recognizes unmethylated CG motifs from the prokaryotic genome. Upon its activation, TLR-9 triggers downstream of the MyD-88-dependent transcriptional activation of NF-κB, and subsequently results in abundant inflammatory cytokines expression that induces a profound inflammatory milieu. The present exploratory investigation aimed at elucidating the potency of schizophyllan for entrapping ODN 1826 (SPG-ODN 1826)-mediated stimulation of TLR-9 in provoking an inflammatory-type response in murine alveolar macrophages. Schizophyllan (SPG), a representative of the β-glucan family, was used in the present study as a nanovehicle for endosomal trafficking of CpG ODN 1826. TEM analysis of SPG-ODN 1826 nanovehicles revealed that the prepared nanovehicles are spherical and have an average size of about 100 nm. Interestingly, SPG-ODN 1826 nanovehicles were competent in delivering their therapeutic payload within endosomes of murine alveolar macrophage (J774A.1) cells. Exposure of these nanovehicles within LPS stimulated J774A.1, resulted in a significant provocation of reactive oxygen species (ROS) (p &lt; 0.01) in comparison to CpG ODN 1826 alone. Moreover, the formulated nanovehicles succeeded in generating a profound Th1-based cytokine profile constituted by enhanced expression of IFN-γ (p &lt; 0.001) and IL-1β (p &lt; 0.001) inflammatory cytokines. These findings clearly indicated the immunostimulatory potential of SPG-ODN 1826 nanovehicles for inducing the Th1-type phenotype, which would certainly assist in skewing M2 phenotype into the much-desired M1 type during lung cancer

Dissolution and bioavailability improvement of bioactive apigenin using solid dispersions prepared by different techniques

Apigenin (APG) is a poorly soluble bioactive compound/nutraceutical which shows poor bioavailability upon oral administration. Hence, the objective of this research work was to develop APG solid dispersions (SDs) using different techniques with the expectation to obtain improvement in its in vitro dissolution rate and in vivo bioavailability upon oral administration. Different SDs of APG were prepared by microwave, melted and kneaded technology using pluronic-F127 (PL) as a carrier. Prepared SDs were characterized using “thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) spectrometer, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM)”. After characterization, prepared SDs of APG were studied for in vitro drug release/dissolution profile and in vivo pharmacokinetic studies. The results of TGA, DSC, FTIR, PXRD and SEM indicated successful formation of APG SDs. In vitro dissolution experiments suggested significant release of APG from all SDs (67.39–84.13%) in comparison with control (32.74%). Optimized SD of APG from each technology was subjected to in vivo pharmacokinetic study in rats. The results indicated significant improvement in oral absorption of APG from SD prepared using microwave and melted technology in comparison with pure drug and commercial capsule. The enhancement in oral bioavailability of APG from microwave SD (319.19%) was 3.19 fold as compared with marketed capsule (100.00%). Significant enhancement in the dissolution rate and oral absorption of APG from SD suggested that developed SD systems can be successfully used for oral drug delivery system of APG. Keywords: Apigenin, Microwave technology, Pluronic-F127, Solid dispersion, Bioavailabilit