Molecular insights and therapeutic implications of nanoengineered dietary polyphenols for targeting lung carcinoma: part I.

Lung cancer is the second leading cause of cancer-related mortality globally, and non-small-cell lung cancer accounts for most lung cancer cases. Nanotechnology-based drug-delivery systems have exhibited immense potential in lung cancer therapy due to their fascinating physicochemical characteristics, in vivo stability, bioavailability, prolonged and targeted delivery, gastrointestinal absorption and therapeutic efficiency of their numerous chemotherapeutic agents. However, traditional chemotherapeutics have systemic toxicity issues; therefore, dietary polyphenols might potentially replace them in lung cancer treatment. Polyphenol-based targeted nanotherapeutics have demonstrated interaction with a multitude of protein targets and cellular signaling pathways that affect major cellular processes. This review summarizes the various molecular mechanisms and targeted therapeutic potentials of nanoengineered dietary polyphenols in the effective management of lung cancer.

Molecular insights and therapeutic implications of nanoengineered dietary polyphenols for targeting lung cancer: part II.

Flavonoids represent a major group of polyphenolic compounds. Their capacity to inhibit tumor proliferation, cell cycle, angiogenesis, migration and invasion is substantially responsible for their chemotherapeutic activity against lung cancer. However, their clinical application is limited due to poor aqueous solubility, low permeability and quick blood clearance, which leads to their low bioavailability. Nanoengineered systems such as liposomes, nanoparticles, micelles, dendrimers and nanotubes can considerably enhance the targeted action of the flavonoids with improved efficacy and pharmacokinetic properties, and flavonoids can be successfully translated from bench to bedside through various nanoengineering approaches. This review addresses the therapeutic potential of various flavonoids and highlights the cutting-edge progress in the nanoengineered systems that incorporate flavonoids for treating lung cancer.

In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan beads using Gastroplus™.

The objective of present investigation was to develop gastro-retentive controlled release system of carvedilol using biological macromolecule, chitosan. 32 full factorial design was adopted for optimization of tripolyphosphate (X1) and curing time (X2). Bead stability in 0.1N HCl, buoyancy duration, density, drug loading, dissolution efficiency and cumulative percentage release at 8th hour were evaluated as dependent variables. The levels of X1 and X2 of optimized formulation having maximum desirability was found to 2.0% w/v and 62.66min, respectively. The in silico predicted responses and observed response were found to be in good agreement (percent bias error: -13.295 to +13.269). SEM images showed numerous pores in the cross sectional image that renders buoyancy. AUC0-∞ of optimized formulation was 1.47 times higher as compared to suspension corroborating enhanced extent of absorption. Tmax and mean residence time were significantly higher from optimized formulation vis a vis suspension. In silico study indicated maximum regional absorption from the duodenum (94.1%) followed by jejunum (5.6%). Wagner-Nelson and Loo-Reigelman method were the preferred deconvolution approach over numerical deconvolution to establish IVIVC. In conclusion, the study showed that gastro-retentive controlled release system prepared using chitosan could be a potential drug carrier of carvedilol with improved bioavailability.

Solidified self nano-emulsifying drug delivery system of rosuvastatin calcium to treat diet-induced hyperlipidemia in rat: in vitro and in vivo evaluations.

The present work focuses on preparing a solidified self nano-emulsifying drug-delivery system (S-SNEDDS) to improve the in vitro dissolution of rosuvastatin and to evaluate its antihyperlipidemic activity. Powder flow characterization demonstrated good flow properties. The drug-excipient compatibility study indicates no possible interaction. Transmission electron microscopy and scanning electron microscopy revealed nonaggregated, spherical nanosized globules. The globule-size analysis revealed droplet size in nanorange (∼100 nm). S-SNEDDS exhibited improved drug release (∼95%) as compared with rosuvastatin powder (51.89%) at 60 min. Upon antihyperlipidemic study, S-SNEDDS after 14th day of treatment revealed significant reduction in cholesterol (33.47%), triglycerides (40.77%) and atherogenic index (81.28%), while high-density lipoprotein (118.43%) was increased. The study indicates the great potential of S-SNEDDS for improving oral absorption of such poorly soluble drugs and their pharmacodynamic efficacy.

OLANZAPINE-PEG 6000 BINARY SYSTEMS: IN VITRO DISSOLUTION BEHAVIOR, PHYSICOCHEMICAL CHARACTERIZATION AND MATHEMATICAL MODELING.

The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with PEG 6000. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were characterized by X-ray diffraction, differential scanning calorimetry, FT-IR spectroscopy, Near Infrared, Raman analysis and wettability studies. The phase solubility studies and its thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions than pure drug and a linear increase in drug release was observed with an increase in carrier content. XRD, DSC, FT-IR, NIR and Raman analysis revealed the crystallinity reduction of olanzapine and its compatibility with the carrier. Wettability studies proved the increased wettability in samples due to water absorbing nature of the carrier. The possible mechanisms for increased release rate are attributed to solubilization effect of the carrier, formation of solid solution, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity, increased wettability and dispersability of drug in dissolution medium. The suggested reasons for such release behavior were found to be well supported by results of the evaluation techniques.

Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with mannitol. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were selected from release data, dissolution parameters and their release profiles. Solid state characterization techniques like Fourier transform infrared (FT-IR) spectroscopy, X-ray diffractometry, differential scanning calorimetry, near-infrared and Raman spectroscopy were used to characterize the drug in selected dispersions. The dispersions were also evaluated by wettability studies and permeation studies. The results of phase solubility studies and the thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions compared to pure drug, and the release was found to increase with an increase in carrier content. The possible mechanism for increased release rate from dispersions may be attributed to solubilization effect of the carrier, change in crystal quality, phase transition from crystalline to amorphous state, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity of the drug, and increased wettability and dispersability of the drug in dissolution medium. The suggested reasons for increased release rate from dispersions were found to be well supported by results of solid state characterization, wettability and permeation studies. The absence of any interaction between the drug and the carrier was also proved by FT-IR analysis.

O objetivo do presente trabalho é estudar o comportamento de dissolução da olanzapina a partir de suas dispersões sólidas de manitol. As dispersões sólidas foram preparadas por dispersão por fusão e caracterizadas por estudos de solubilidade de fase, conteúdo de fármaco e dissolução in vitro. As melhores dispersões quanto à liberação foram selecionadas a partir dos dados de liberação, parâmetros de dissolução e perfis de liberação. Técnicas de caracterização de estado sólido como espectroscopia no infravermelho pela transformada de Fourier (FTIR), difratometria de raios X, calorimetria de varredura diferencial, infravermelho próximo e espectroscopia Raman foram utilizadas para caracterizar os fármacos a partir das dispersões selecionadas. As dispersões foram, também, avaliadas pelos estudos de capacidade de umedecimento e permeação. Os resultados dos estudos de solubilidade de fase e os parâmetros termodinâmicos indicaram a espontaneidade e o efeito de solubilização do transportador. Os resultados dos estudos de liberação mostraram maior aperfeiçoamento da liberação do fármaco das dispersões sólidas, comparativamente à do fármaco puro, e descobriu-se que a liberação aumenta com o aumento do conteúdo de transportador. O mecanismo possível para o aumento da taxa de liberação das dispersões pode ser atribuído ao efeito de solubilização do transportador, mudança da qualidade do cristal, transição de fase cristalina para estado amorfo, prevenção da aglomeração ou agregação das partículas do fármaco, mudança na superfície de hidrofobicidade do fármaco e aumento da capacidade de umedecimento e dispersividade do fármaco no meio de dissolução. As razões sugeridas para o aumento da taxa de liberação a partir das dispersões foram apoiadas pelos resultados da caracterização do estado sólido, capacidade de umedecimento e pelos estudos de permeação. A ausência de qualquer interação entre o fármaco e o transportador foi, também, comprovada pela análise no FTIR.

Eudragit-based transdermal delivery system of pentazocine: Physico-chemical, in vitro and in vivo evaluations.

The present study was aimed to develop a matrix-type transdermal formulation of pentazocine using mixed polymeric grades of Eudragit RL/RS. The possible interaction between drug and polymer used were characterized by FTIR, DSC and X-RD. X-RD study indicates a change of state of drug from crystalline to amorphous in the matrix films prepared. The matrix transdermal films of pentazocine were evaluated for physical parameters and in vitro dissolution characteristic using Cygnus' sandwich patch holder. Irrespective of the grades of Eudragit polymer used, the thickness and weight per patch were similar. In vitro dissolution study revealed that, with an increase in the proportion of Eudragit RS (slightly permeable) type polymer, dissolution half life (t(50%)) increases and dissolution rate constant value decreases. Selected formulations were chosen for these pharmacokinetic studies in healthy rabbits. The relevance of difference in the in vitro dissolution rate profile and pharmacokinetic parameters (C(max), t(max), AUC((s)), t(1/2,) K(el), and MRT) were evaluated statistically. In vitro dissolution profiles (DRC and t(50%)) and pharmacokinetic parameters showed a significant difference between test products (P<0.01). Quantitatively good correlation was found between the percentage of drug absorbed from the transdermal patches and AUC((s)).

Development of matrix controlled transdermal delivery systems of pentazocine: In vitro/in vivo performance.

The present study aimed to develop hydroxypropyl methylcellulose based transdermal delivery of pentazocine. In formulations containing lower proportions of polymer, the drug released followed the Higuchi kinetics while, with an increase in polymer content, it followed the zero-order release kinetics. Release exponent (n) values imply that the release of pentazocine from matrices was non-Fickian. FT-IR, DSC and XRD studies indicated no interaction between drug and polymer.The in vitro dissolution rate constant, dissolution half-life and pharmacokinetic parameters (C(max), t(max), AUC(s), t(1/2), Kel, and MRT) were evaluated statistically by two-way ANOVA. A significant difference was observed between but not within the tested products. Statistically, a good correlation was found between per cent of drug absorbed from patches vs. C(max) and AUC(s). A good correlation was also observed when per cent drug released was correlated with the blood drug concentration obtained at the same time point. The results of this study indicate that the polymeric matrix films of pentazocine hold potential for transdermal drug delivery.