Synthesis, characterisation and in vitro anticancer activity of conjugated protease inhibitor-silver nanoparticles (AgNPs-PI) against human breast MCF-7 and prostate PC-3 cancer cell lines.

The conjugated silver nanoparticles using biomolecules have attracted great attention of researchers because physical dimensions and surface chemistry play important roles in toxicity and biocompatibility of AgNPs. Hence, in the current study, synthesis of bio-conjugated AgNPs with protein protease inhibitor (PI) isolated from Streptomyces spp. is reported. UV-visible spectra of PI and AgNPs showed stronger peaks at 280 and 405 nm, confirming the synthesis of conjugated AgNPs-PI. TEM and SEM images of AgNPs-PI showed spherical-shaped nanoparticles with a slight increase in particle size and thin amorphous layer around the surface of silver nanomaterial. Circular dichroism, FT-IR and fluorescence spectral studies confirmed AgNPs-PI conjugation. Conjugated AgNPs-PI showed excellent anticancer potential than AgNPs and protease inhibitor separately on human breast MCF-7 and prostate PC-3 cell lines. The findings revealed that surface modification of AgNPs with protein protease inhibitor stabilised the nanomaterial and increased its anticancer activity.

Development of an Analytical Quality by Design RP-HPLC Method and Its Validation for Estimation of Gefitinib From Bulk, Tablet Dosage Form, and Complex Nanoformulation.

BACKGROUND: Estimation of the drug and development of the method is a critical aspect of formulation development and a critical factor for analytical scientists. Gefitinib is a poorly soluble anticancer drug. OBJECTIVE: The present research focuses on the topic of the development of innovative quality by design methods for the estimation of gefitinib (GF) from bulk, pharmaceutical tablet formulation, and complex nanoformulations. METHODS: To simplify the estimation of poorly soluble drugs such as GF, response surface methodology (RSM) was adopted with effective leverages to obtain precise computation design space using the Box-Behnken design (BBD) model. The major three mixed-effect independent factors (percentage of buffer, pH of buffer, and flow rate) were screened with three prominent dependent responses (viz., theoretical plate, retention time, and tailing factor) selected for optimal analysis. Furthermore, co-processed steps were employed for the estimation of the analyte from the complex formulation. RESULTS: The RP-HPLC method uses the quality by design (QbD) approach can effectively estimate the analyte concentration of less than 4.5 min. The developed method was economically robust and sensitive and shows a relative standard deviation (RSD, %) of less than 2% for all the selected validation parameters. The estimated design space suggests the highest desirability (R2-0.998) at 60% of buffer in the mobile phase, pH 4.25, and flow rate of 0.7 mL/min. CONCLUSIONS: The QbD approach was used to design and develop the method by understanding the interaction between dependent and independent variables to get the optimum values. The developed method was validated successfully and can be useful for formulation scientists to estimate drug concentration and drug release profiles from complex nanoformulations. HIGHLIGHTS: The analytical approach was designed and quantified using a quality-by-design approach to make the RP-HPLC method more robust and efficient for the estimation of analytes from complex nanoformulations. The method is also useful to eliminate the interfering molecule during estimation by employing co-processing steps. The developed method saves time and cost of solvent and employs QbD as a requirement of recent regulatory concern.

Recent Developments in Tyrosine Kinase Inhibitor-based Nanotherapeutics for EGFR-resistant Non-small Cell Lung Cancer.

The advent of drug resistance in response to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitor (TKI) targeted therapy represents a serious challenge in the management of non-small cell lung cancer (NSCLC). These acquired resistance mutations, attributed to several advanced EGFR mutations and, necessitated the development of new-generation TKIs. Nanomedicine approaches provide a plausible way to address these problems by providing targeted delivery and sustained release, which have demonstrated success in preclinical trials. This review article provides a summary of nano-formulations designed for EGFR-TKI-resistant NSCLC, highlighting their efficacy in both in vitro and in vivo models. These findings reveal insights into the design of nanoparticles and multifunctional nanosystems, offering a potential avenue for efficacious treatment of EGFR-TKIresistant NSCLC.

Development of olanzapine solid dispersion by spray drying technique using screening design for solubility enhancement.

Introduction: Olanzapine (OLZ) is a psychotropic class drug commonly used to treat schizophrenia, bipolar disorder, and acute manic episodes. It has less water solubility, resulting in a slow dissolution rate and oral bioavailability. Therefore, the development in oral dosage forms is required to enhance the drug solubility. Method: The solid dispersion of olanzapine is prepared by spray drying technique. The solution of polyvinylpyrrolidone K-30 (PVP K-30), mono amino glycyrrhizinate pentahydrate (GLY), OLZ and silicon dioxide were dissolved in distilled water and ethanol and spray dried to get the solid dispersion. Solid dispersion was characterized for surface morphology, solubility, encapsulation efficiency (EE), X-ray diffraction (X-RD), Differential Scanning Calorimeter (DSC) and drug-polymer interaction by Fourier transforms infrared spectroscopy. Results: The amorphous nature of the drug's incorporation in solid dispersion was confirmed by X-RD analysis. Prepared solid dispersion showed higher solubility, 11.51 mg, than pure OLZ (0.983 mg ml-1), while the range of EE was found to be between 64 to 90 %. Conclusions: The solubility and dissolution rate of the OLZ can effectively increase by spray-dried solid dispersion. Plackett-Burman screening design plays a vital role in understanding the effect of independent variables on EE and solubility.

Sulfobutylether-ß-cyclodextrin: A functional biopolymer for drug delivery applications.

Sulfobutylether ß-cyclodextrin (SBE-ß-CD) is a polyanionic cyclic oligosaccharide that contains glucopyranose units forming a torus ring-like structure. SBE-ß-CD is gifted with many favorable properties viz. relatively high solubility (>50 folds compared to ß-CD), improved stability, and biocompatibility that praised SBE-ß-CD as a smart polymer for drug delivery applications. Commercially, SBE-ß-CD is popular by its brand name Captisol®. The present review discusses the structure, properties, and preparation methods of SBE-ß-CD-based inclusion complexes (ICs). Furthermore, we discuss here the preparation and applications of SBE-ß-CD ICs-based nanoparticulate drug delivery systems, which combines the merits of both, ICs (enhanced solubility) and nanoparticles (NPs, targeted therapy). Patents on and FDA-approved Captisol®-enabled products are tabulated in the benefit of readers. The toxicological aspects and current clinical status of SBE-ß-CD or SBE-ß-CD-based products are briefly explained in the present review. In our opinion, the present review would be a pathfinder to allow dissemination of information on SBE-ß-CD.

Statistical optimization of voriconazole nanoparticles loaded carboxymethyl chitosan-poloxamer based in situ gel for ocular delivery: In vitro, ex vivo, and toxicity assessment.

The research study reflects the development of novel voriconazole (VCZ) loaded nanoparticles (NPs) for prolonged delivery for the management of ocular diseases. The in situ ophthalmic gel was prepared by incorporating NPs into carboxymethyl chitosan (CMCh) and poloxamer. The central composite design was used to optimize the process for the preparation of nanoparticles by the o/w solvent evaporation method. The developed nanoparticles were evaluated for the encapsulation efficiency (89.6 ± 1.2%), particle size (219.3 ± 1.8 nm), polydispersity index (PDI, 0.1), zeta potential (- 21.1 ± 1.12 mV), saturation solubility, DSC study, and drug release. The etherification process grafts carboxyl surface functional groups, on chitosan, and was confirmed by FTIR and NMR studies. The developed CMCh-poloxamer based gelling system was found to be clear and transparent with gelation temperature varying from 33 to 40 °C. The nanoparticle-loaded gel containing CMCh demonstrated enhanced antifungal activity against Candida albicans. The optimized batch containing CMCh showed improved mucoadhesion by 2.86-fold compared to VCZ nanosuspension. The drug release was prolonged up to 8 h with an ex vivo study suggesting the enhanced permeation across goat cornea estimated via fluorescent microscope. The hen's egg chorioallantoic membrane study revealed that the formulation was non-irritant and tolerated by the chorioallantoic membrane. The present study concludes that the VCZ loaded nanoparticulate in situ ophthalmic gel using CMCh may act as a potential alternative for traditional eye drops.

Effect of process parameters on the recovery of lactose in an antisolvent acetone/acetone-ethanol mixture: A comparative study based on sonication medium.

Recovery of lactose from the whey using sonocrystallization was studied experimentally. The effect of sonication medium and irradiation power levels was evaluated using three different ultrasonic equipments. Effects of various parameters such as sonication time, pH of the medium, antisolvent (acetone and acetone-ethanol mixture) and concentration of lactose were determined. The optimal parametric conditions were analyzed using differential scanning calorimetry, thermogravimetric analysis, particle size distribution, and zeta potential measurements. Overall, the highest lactose recovery was obtained using a mixture of acetone and ethanol as antisolvent in bath sonication as well as atomization process.

Nanogels as nanocarriers for drug delivery: A review.

Nanogels are submicron-size aqueous dispersions of water-swollen particles, composed of nano-sized three-dimensional highly cross-linked networks of hydrophilic polymers. An active pharmaceutical agent or therapeutic agent with high or low molecular weight can be easily encapsulated into nanogels that can be delivered to the site of action via various routes, including oral, pulmonary, nasal, parenteral and intraocular routes, among others. Therapeutic agents encapsulated into nanogels improve the therapeutic activity in the biological environment. The application of different nanogels in drug delivery and recent clinical trial studies has been described concisely in this review.

Sustainable Drug Delivery of Famotidine Using Chitosan-Functionalized Graphene Oxide as Nanocarrier.

This work mainly focuses on the graphene oxide (GO)-assisted sustainable drug delivery of famotidine (FMT) drug. Famotidine is loaded onto GO and encapsulated by chitosan (CH). UV-visible spectroscopy, field emission scan electron microscopy, and atomic force microscopy confirm the loading of FMT on GO. An interaction of FMT with GO and CH through amine functionalities is confirmed by Fourier-transform infrared spectroscopy. Differential scanning calorimetric and cyclic voltammetric investigations confirm the compatibility of FMT and its retaining activity within chitosan-functionalized graphene oxide (CHGO) composite. Encapsulation efficiency of FMT is determined for various CHGO-FMT combinations and found to be higher at 1:9 ratio. The in vitro drug release profile is studied using a dissolution test apparatus in 0.1 m phosphate buffer medium (pH = 4.5), which shows sustainable drug release up to 12 h, which is greater than the market product (Complete release within 2 h). Comparative study of drug encapsulated with CH and without GO elucidates that GO is responsible for the sustainable release. The "n" value obtained from slope using Korsmeyer-Peppas model suggests the super case-II transport mechanism.

Screening of process variables to enhance the solubility of famotidine with 2-HydroxyPropyl-ß-Cyclodextrin & PVP K-30 by using Plackett-Burman design approach.

In the present work, inclusion complex of famotidine (FMT) was prepared with (2-HydroxyPropyl)-ß-Cyclodextrin (HP-ß-CyD) and polyvinylpyrrolidone K-30 (PVP K-30) by spray drying technique to enhance the solubility of famotidine. FMT is a potent histamine H2-receptor antagonist having low solubility as well as oral bioavailability. In order to enhance the solubility of FMT, a quality by design (QbD) approach has been used by employing Plackett-Burman design (PBD). With the application of PBD, seven independent process variables were investigated and optimized for maximum solubility. The developed inclusion complex was characterized for solubility, encapsulation efficiency, FTIR, FESEM, XRD. In-vitro drug release study was also performed by preparing fast dissolving tablets of inclusion complex. Solubility of FMT in prepared complex was found 38 fold higher than pure FMT while %EE was found 92.10%. Statistical analysis of the data (ANOVA) indicates an adequate model fitting predicting the effect of process parameters affecting the solubility. In conclusion, spray dried inclusion complex can effectively increases the solubility as well as dissolution rate of the FMT and other active pharmaceutical ingredients in combination of the fast dissolving tablets.

Development of floating chitosan-xanthan beads for oral controlled release of glipizide.

INTRODUCTION: The aim of the present work was to develop controlled release, floating and mucoadhesive beads of glipizide by using the polyionic complexation technique. Plasma half-life of glipizide being 2-4 h was selected for development of controlled release dosage form. METHODS: Formulation batches were designed by employing chitosan as cationic and xanthan gum as anionic polymers. In vitro drug release was evaluated for the period of 24 h in phosphate buffer pH 7.4. RESULTS: Sustained release of drug was observed in all formulation batches with % drug release ranging from 87.50% to 100.67%, no significant effect on the drug release was observed after varying chitosan to xanthan gum ratio. Encapsulation efficiency was found to be in the range of 79.48 ± 1.10-94.48 ± 1.52. In vitro bioadhesion studies showed that beads had satisfactory bioadhesive strength ranging from 67.11% ± 1.73% to 93.12% ± 1.56%. Buoyancy studies revealed that beads possess comparable floating capacity in the gastric fluids. Swelling kinetics was carried in pH 1.2 and 7.4 buffers. Significant difference (P < 0.05) in swelling kinetics was observed. Drug to polymer interaction was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry studies. Scanning electron microscopy studies revealed that formed beads were discrete with rough and wrinkled surfaces. CONCLUSIONS: In conclusion, beads were successfully formed by employing chitosan and xanthan gum and showed to possess sustained release effect. Beads also showed pH dependent swelling kinetics, this property can also be applied for the drugs which are susceptible to the acidic environment in the stomach, and comparable bioadhesive and floating properties were also observed.

Optimization of sustained release aceclofenac microspheres using response surface methodology.

Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14±0.015% to 85.34±0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12h. The optimized microspheres formulation showed E.E. of 84.87±0.005 with small error value (1.39). The low magnitudes of error and the significant value of R(2) in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects.

Aceclofenac microspheres: quality by design approach.

The purpose of this study was to prepare polymeric microspheres containing aceclofenac by single emulsion [oil-in-water (o/w)] solvent evaporation method. Two biocompatible polymers, ethylcellulose, and Eudragit® RS100 were used in combination. Seven processing factors were investigated by Plackett-Burman design (PBD) in order to enhance the encapsulation efficiency of the microspheres. A Plackett-Burman design was employed by using the Design-Expert® software (Version-8.0.7.1). The resultant microspheres were characterized for their size, morphology, encapsulation efficiency, and drug release. Imaging of particles was performed by field emission scanning electron microscopy. Interaction between the drug and polymers were investigated by Fourier transform infrared (FTIR) spectroscopy, and X-ray powder diffractometry (XRPD). Graphical and mathematical analyses of the design showed that Eudragit® RS100, and polyvinyl alcohol (PVA) were significant negative effect on the encapsulation efficiency and identified as the significant factor determining the encapsulation efficiency of the microspheres. The low magnitudes of error and the significant values of R(2) in the present investigation prove the high prognostic ability of the design. The microspheres showed high encapsulation efficiency (70.15% to 83.82%). The microspheres were found to be discrete, oval with smooth surface. The FTIR analysis confirmed the compatibility of aceclofenac with the polymers. The XRPD revealed the dispersion of drug within microspheres formulation. Perfect prolonged drug release profile over 12h was achieved by a combination of ethylcellulose, and Eudragit® RS100 polymers. In conclusion, polymeric microspheres containing aceclofenac can be successfully prepared using the technique of experimental design, and these results helped in finding the optimum formulation variables for encapsulation efficiency of microspheres.

Preparation and In Vitro Evaluation of Ethylcellulose and Polymethacrylate Resins Loaded Microparticles Containing Hydrophilic Drug.

Objective. The purpose of the recent study was to prepare and estimate sustained release of Ethylcellulose (300 cps) and Eudragit (RS 100 and RL 100) microparticles containing Propranolol hydrochloride used as a treatment of cardiovascular system, especially hypertension. Method. Propranolol hydrochloride was microencapsulated with different polymers (Ethylcellulose, Eudragit RS, and Eudragit RL) using modified hydrophobic (O/O) solvent evaporation method using 1 : 1 combination of acetone and isopropanol as the internal phase. Obtained microparticles were showing higher batch yield with higher encapsulation efficiency. Microparticles were prepared with different ratios of 1 : 1, 1 : 3, 1 : 5, and 1 : 7 (%, wt/wt) using span 80 (%, v/v) as a surfactant. Results. The influence of formulation factors like drug: polymer ratio, internal phase, and type of polymers on obtained microparticles was characterized with respect to particle size distribution, encapsulation efficiency, percentage yield, FTIR, and FE-SEM. Higher encapsulation efficiencies were obtained with various polymers like Ethylcellulose (96.63 ± 0.5) compared to Eudragit RS 100 (83.70 ± 0.6) and RL 100 (89.62 ± 0.6). The in vitro release study was characterized by initial burst. Conclusion. The result of study displays that Ethylcellulose and Eudragit loaded microparticles of Propranolol hydrochloride can be effectively prepared using modified hydrophobic emulsification solvent evaporation technique. Therefore, the modified hydrophobic emulsion technique can also be applied to the preparation of microparticles for low molecular weight and highly water soluble drugs.

Removal of Brilliant Green from wastewater using conventional and ultrasonically prepared poly(acrylic acid) hydrogel loaded with kaolin clay: A comparative study.

The present work deals with the removal of Brilliant Green dye from wastewater using a poly(acrylic acid) hydrogel composite (PAA-K hydrogel) prepared by incorporation of kaoline clay. The composite has been synthesized using ultrasound assisted polymerization process as well as the conventional process, with an objective of showing the better effectiveness of ultrasound assisted synthesis. It has been observed that the hydrogel prepared by ultrasound assisted polymerization process showed better results. The optimum conditions for the removal of dye are pH of 7, temperature of 35°C, initial dye concentration of 30mg/L and hydrogel loading of 1g. The extent of removal of dye increased with an increase in the contact time and initial dye concentration. A pseudo-second-order kinetic model has been developed to explain the adsorption kinetics of dye on the PAA-K hydrogel. Thermodynamic and kinetic parameters indicate that the adsorption process is spontaneous in nature and the PAA-K hydrogel prepared by ultrasound process is a promising adsorbent compared to conventional process. The obtained adsorption data has also been fitted into commonly used adsorption isotherms and it has been found that Freundlich as well as Langmuir adsorption isotherm models fits well to the experimental results.

Synthesis and pharmacological evaluation of novel 1-(2-(benzoyl-substituted-2-phenyl-1H-indol-5-carbony) hydrazinyloxy) vinyl nitrate derivatives as potent non-ulcerogenic, analgesic and anti-inflammatory agents.

Six derivatives of 1-(2-(benzoyl-(substituted)-2-phenyl-1H-indole-5-carbony) hydrazinyloxy) vinyl nitrate were synthesized and tested in vivo for anti-inflammatory, analgesic, and ulcerogenic properties. Synthesized compounds shown significant anti-inflammatory activity comparable to that of Diclofenac sodium in the carrageenan-induced rat paw edema test and all of the compounds were found to be equipotent to Diclofenac sodium in the acetic acid induced writhing analgesic model. Out of six derivatives two derivatives found to produce no ulceration in stomach specimen of rats; nitric oxide seems to contribute to their excellent safety profile which supports several endogenous GIT defense mechanisms, including increase in mucus, bicarbonate secretions, increase in mucosal blood flow, and inhibition of the activation of pro-inflammatory cells by which NO-Indomethacin protects GI mucosa.