Preparation and Characterization of Chitosan and Inclusive Compound-Layered Gold Nanocarrier to Improve the Antiproliferation Effect of Tamoxifen Citrate in Colorectal Adenocarcinoma (Caco-2) and Breast Cancer (MCF-7) Cells.

Objectives: Cancer diseases have been linked to a huge number of causes that led to deaths in this century along with cardiovascular and lung diseases. Most death-leading types of cancer are colon, lung, breast, and prostate cancers. Due to the remarkable properties of gold (Au) nanocarrier, they are used to deliver and improve tamoxifen (Tam) citrate activity in Caco-2 and MCF-7 cells. Materials and Methods: In this study, preparation of Au nanoparticles (NPs), zeta-potential and size, high resolution transient electron microscopy (HRTEM), high-performance liquid chromatography, ultraviolet-visible spectra, fluorescence microscopy, fourier infrared spectroscopy, and real-time cellular analysis xCELLigence technology were investigated. Results: The zeta-average size of the Tam- ß-cyclodextrin (ß-CD)-hyaluronic acid (HA)-chitosan (Chi)-Au nanocomposite is 82.02 nm with a negative zeta potential of -23.6. Furthermore, HRTEM images showed that, successful formulation of polymer shell around Au core and the Au NP shape is mostly spherical, triangle and irregular. Furthermore, the fluorescence microscope image showed proper cellular uptake of the Tam-ß-CD-HA-Chi-Au nanocomposite in MCF-7 and Caco-2 cells. Additionally, Tam-ß-CD-HA-Chi-Au nanocomposite significantly improved the cytotoxic activity of Tam citrate on Caco-2 cells. IC50 value of Tam reduced from 8.55 µM to 5.32 µM, after 48 h of incubation time (p value <0.00001). Conclusion: This study showed that Tam-ß-CD-HA-Chi-Au nanocomposite is a potential nanocarrier for delivering the drug to Caco-2 and MCF-7 cancer cells, since it has improved Tam citrate activity on colorectal cancer cells. After all, the developed formula showed more effect on Caco-2 than MCF-7. The prepared nanocomposite could be used to improve the cancer therapy in clinical trials.

Novel controlled ionic gelation strategy for chitosan nanoparticles preparation using TPP-ß-CD inclusion complex.

The aim of this study was to develop a novel controlled ionic gelation strategy for chitosan nanoparticle preparation to avoid particle aggregation tendency associated with conventional ionic gelation process. In this study inclusion complexation behaviour of sodium tripolyphosphate (TPP) with beta cyclodextrin (ß-CD) has been investigated. The TPP-ß-CD inclusion complex was characterized by FT-IR, XRD and DSC techniques. The complexation behaviour was also investigated by molecular docking study. The results showed that the TPP molecule formed inclusion complex with ß-CD. Further, TPP-ß-CD inclusion complex was used to prepare chitosan nanoparticles. The chitosan nanoparticles based on TPP-ß-CD inclusion complex had smaller size of 104.2nm±0.608, good PDI value of 0.346±0.016 and acceptable zeta potential of +27.33mV±0.416. The surface characteristics of chitosan nanoparticles were also observed with transmission electron microscopy. Results indicates that TPP-ß-CD inclusion complex can be used for the formation of chitosan nanoparticles with smaller and more uniform particle size in comparison to conventional TPP based chitosan nanoparticles.

Development and evaluation of glyceryl behenate based solid lipid nanoparticles (SLNs) using hot self-nanoemulsification (SNE) technique.

The purpose of this research was to improve oral bioavailability of poorly aqueous soluble drug lopinavir using solid lipid nanoparticles (SLNs). Glyceryl behenate based SLNs of lopinavir were prepared using hot self-nanoemulsification (SNE) technique. The hot isotropic mixture of glyceryl behenate, Poloxamer 407 and polyethylene glycol 4000 was spontaneously self-nanoemulsify in hot water (80 °C) and SLNs were subsequently formed with rapid cooling. Hot SNE ability of isotropic mixture was visually assessed by ternary phase diagram study. Optimized SLNs were having particle size of 214.5 ± 4.07 nm, entrapment efficiency of 81.6 ± 2.3 % and zeta potential of -12.7 ± 0.87 mV. SLNs were evaluated by transmission electron microscopy and atomic force microscopy for morphological details. Further, differential scanning calorimetry and x-ray diffraction were also performed for solid state characterization of SLNs. Higher oral bioavailability (3.56-fold) was found for lopinavir loaded SLNs in comparison to bulk lopinavir due to higher lymphatic drug transport (p < 0.05). Results indicate that SLNs of glyceryl behenate can be successfully prepared by hot SNE technique.

Spectroscopic investigation on the inclusion complex formation between amisulpride and γ-cyclodextrin.

The purpose of this research was to investigate inclusion complex formation between poorly soluble drug amisulpride (AMI) and γ-cyclodextrin (γ-CD). The solubility of AMI was enhanced by formation of inclusion complex of AMI with nano-hydrophobic cavity of γ-CD. The stoichiometry of inclusion complex was studied by continuous variation Job's plot method and found 1:1. The binding constant was found 1166.65 M(-1) by Benesi-Hildebrand plot. The molecular docking of AMI and γ-CD was done to investigate complexation. The inclusion complex formation was further confirmed by (1)H NMR and FT-IR, DSC and XRD analysis. The solubility of AMI was increased 3.74 times after inclusion complex formation with γ-CD.

Development of solid lipid nanoparticles (SLNs) of lopinavir using hot self nano-emulsification (SNE) technique.

Solid lipid nanoparticles (SLNs) of poor orally bioavailable drug lopinavir were prepared using hot self nano-emulsification (SNE) technique. Hot isotropic mixture of stearic acid, poloxamer and polyethylene glycol was spontaneously self nano-emulsify in hot water and SLNs were formed with subsequent rapid cooling. Self nano-emulsification ability of stearic acid, poloxamer and polyethylene glycol mixture was assessed by ternary phase diagram study. Optimized SLNs were having particle size of 180.6 ± 2.32 nm (PDI=0.133 ± 0.001), 91.5 ± 1.3% entrapment efficiency and zeta potential of -13.4 ± 0.56 mV. SLNs were evaluated by transmission electron microscopy (TEM) and atomic force microscopy (AFM) for morphological study. Further, Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) of SLNs were also performed for checking solid state characterization. Higher oral bioavailability was found for lopinavir loaded SLNs in comparison to bulk lopinavir due to higher lymphatic drug transport (p<0.05). Results indicate that SLNs of higher fatty acids can be successfully prepared by hot SNE technique.

Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL.

The purpose of this study was to investigate effect of bioadhesion on the initial in vitro buoyancy behaviour of effervescent matrix tablets of ciprofloxacin HCl (CIPRO). Tablets were prepared by direct compression using HPMC K4M and Carbopol 971P as hydrophilic-controlled release polymers, sodium bicarbonate (NaHCO(3)) as gas-generating agent, polyplasdone XL, Explotab and Ac-Di-Sol as swelling agents. Tablets were evaluated for normal and modified initial in vitro floating behavior, floating duration, swelling behavior and in vitro drug release studies. A modified buoyancy lag time for tablets was determined in order to include the effect of bioadhesion on initial buoyancy. The initial buoyancy was found depended on bioadhesion ability of tablets. The lowest modified buoyancy lag time of 20 seconds was obtained for Formulation F7 having both NaHCO(3) and polyplasdone XL. The floating duration was also found dependent on concentration of NaHCO(3) and swelling agents. The drug release of F7 was also sustained up to 12-hr duration with anomalous drug transport mechanism.

Formulation, development, and performance evaluation of metoclopramide HCl oro-dispersible sustained release tablet.

The present study was undertaken to develop and evaluate an oro-dispersible, sustained release tablet of metoclopramide HCl. The technology was comprised of developing sustained release microparticles, and compression of resultant microspheres into a fast dispersible tablet by direct compression. The microspheres of metoclopramide HCl were prepared by an emulsification-solvent evaporation method using ethylcellulose as the matrix polymer. The prepared microspheres were evaluated for morphology, particle size, entrapment efficiency, and in vitro drug release characteristics. Scanning electron microscopy demonstrated spherical particles with a mean diameter of 81.27 ± 5.87 µm and the drug encapsulation efficiency was found to be 70.15 ± 3.06%. The process and formulation variables such as rotation speed, polymer concentration, and drug concentration influenced the drug encapsulation efficiency and in vitro drug release. Optimized microspheres were compressed into tablets which were comprised of metoclopramide HCl microspheres, 53% (w/v) of D-mannitol granules, 7% (w/w) of Polyplasdone XL 10, and 0.5% (w/w) of calcium stearate. The tablets demonstrated a hardness of 59 ± 3 N, friability of 0.21% and disintegration time of 27 ± 3 sec. The formulations were subjected to stability studies as per ICH guidelines and were found to be stable after a 6 month study. In vivo experiments conducted in rats demonstrated that a constant level of metoclopramide HCl in plasma could be maintained for up to 20 h at a suitable concentration for antiemetic activity. An appropriate combination of excipients made it possible to obtain orally disintegrating sustained release tablets of metoclopramide HCl using simple and conventional techniques.