Current Pharmaceutical Design - Volume 25, Issue 34, 2019

The in-vitro experimental model for the development of cancer therapeutics has always been challenging. Recently, the scientific revolution has improved cell culturing techniques by applying three dimensional (3D) culture system, which provides a similar physiologically relevant in-vivo model for studying various diseases including cancer. In particular, cancer cells exhibiting in-vivo behavior in a model of 3D cell culture is a more accurate cell culture model to test the effectiveness of anticancer drugs or characterization of cancer cells in comparison with two dimensional (2D) monolayer. This study underpins various factors that cause resistance to anticancer drugs in forms of spheroids in 3D in-vitro cell culture and also outlines key challenges and possible solutions for the future development of these systems.

Background: Biocompatible polymers are gaining great interest in the field of biomedical applications. The term biocompatibility refers to the suitability of a polymer to body and body fluids exposure. Biocompatible polymers are both synthetic (man-made) and natural and aid in the close vicinity of a living system or work in intimacy with living cells. These are used to gauge, treat, boost, or substitute any tissue, organ or function of the body. A biocompatible polymer improves body functions without altering its normal functioning and triggering allergies or other side effects. It encompasses advances in tissue culture, tissue scaffolds, implantation, artificial grafts, wound fabrication, controlled drug delivery, bone filler material, etc. Objectives: This review provides an insight into the remarkable contribution made by some well-known biopolymers such as polylactic-co-glycolic acid, poly(-caprolactone) (PCL), polyLactic Acid, poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), Chitosan and Cellulose in the therapeutic measure for many biomedical applications. Methods: Various techniques and methods have made biopolymers more significant in the biomedical fields such as augmentation (replaced petroleum based polymers), film processing, injection modeling, blow molding techniques, controlled / implantable drug delivery devices, biological grafting, nano technology, tissue engineering etc. Results: The fore mentioned techniques and other advanced techniques have resulted in improved biocompatibility, nontoxicity, renewability, mild processing conditions, health condition, reduced immunological reactions and minimized side effects that would occur if synthetic polymers are used in a host cell. Conclusion: Biopolymers have brought effective and attainable targets in pharmaceutics and therapeutics. There are huge numbers of biopolymers reported in the literature that has been used effectively and extensively.

Background: Natural phytochemicals and their derivatives have been used in medicine since prehistoric times. Natural phytochemicals have potential uses against various disorders, including cancers. However, due to low bioavailability, their success in clinical trials has not been reproduced. Nanotechnology has played a vital role in providing new directions for diagnosis, prevention, and treatment of different disorders, and of cancer in particular. Nanotechnology has demonstrated the capability to deliver conventional natural products with poor solubility or a short half-life to target specific sites in the body and regulate the release of drugs. Among the natural products, the phytoalexin resveratrol has demonstrated therapeutic effects, including antioxidant, antiinflammatory, and anti-proliferative effects, as well as the potential to inhibit the initiation and promotion of cancer. However, low water solubility and extensive first-pass metabolism lead to poor bioavailability of resveratrol, hindering its potential. Conventional dosage forms of resveratrol, such as tablets, capsules, dry powder, and injections, have met with limited success. Nanoformulations are now being investigated to improve the pharmacokinetic characteristics, as well as to enhance the bioavailability and targetability of resveratrol. Objectives: This review details the therapeutic effectiveness, mode of action, and pharmacokinetic limitations of resveratrol, as well as discusses the successes and challenges of resveratrol nanoformulations. Modern nanotechnology techniques to enhance the encapsulation of resveratrol within nanoparticles and thereby enhance its therapeutic effects are emphasized. Conclusion: To date, no resveratrol-based nanosystems are in clinical use, and this review would provide a new direction for further investigations on innovative nanodevices that could consolidate the anticancer potential of resveratrol.

Core-shell polymers represent a class of composite particles comprising of minimum two dissimilar constituents, one at the center known as a core which is occupied by the other called shell. Core-shell molecularly imprinting polymers (CSMIPs) are composites prepared via printing a template molecule (analyte) in the coreshell assembly followed by their elimination to provide the everlasting cavities specific to the template molecules. Various other types of CSMIPs with a partial shell, hollow-core and empty-shell are also prepared. Numerous methods have been reported for synthesizing the CSMIPs. CSMIPs composites could develop the ability to identify template molecules, increase the relative adsorption selectivity and offer higher adsorption capacity. Keen features are measured that permits these polymers to be utilized in numerous applications. It has been developed as a modern technique with the probability for an extensive range of uses in selective adsorption, biomedical fields, food processing, environmental applications, in utilizing the plant's extracts for further applications, and sensors. This review covers the approaches of developing the CSMIPs synthetic schemes, and their application with special emphasis on uses in the biomedical field, food care subjects, plant extracts analysis and in environmental studies.

Water pollution due to waste effluents of the textile industry is seriously causing various health problems in humans. Water pollution with pathogenic bacteria, especially Escherichia coli (E. coli) and other microbes is due to the mixing of fecal material with drinking water, industrial and domestic sewage, pasture and agricultural runoff. Among the chemical pollutants, organic dyes due to toxic nature, are one of the major contaminants of industrial wastewater. Adequate sanitation services and drinking quality water would eliminate 200 million cases of diarrhea, which results in 2.1 million less deaths caused by diarrheal disease due to E. coli each year. Nanotechnology is an excellent platform as compared to conventional treatment methods of water treatment and remediation from microorganisms and organic dyes. In the current study, toxicity and carcinogenicity of the organic dyes have been studied as well as the remediation/inactivation of dyes and microorganism has been discussed. Remediation by biological, physical and chemical methods has been reviewed critically. A physical process like adsorption is cost-effective, but can’t degrade dyes. Biological methods were considered to be ecofriendly and cost-effective. Microbiological degradation of dyes is cost-effective, eco-friendly and alternative to the chemical reduction. Besides, certain enzymes especially horseradish peroxidase are used as versatile catalysts in a number of industrial processes. Moreover, this document has been prepared by gathering recent research works related to the dyes and microbial pollution elimination from water sources by using heterogeneous photocatalysts, metal nanoparticles catalysts, metal oxides and enzymes.

Background: Bacterial cellulose (BC) has been extensively utilized in a wide range of applications specifically in the biomedical field thanks to its excellent physico-chemical and biological features. The major limitation restricting its application in certain areas is its high production cost. Its widespread applications demand exploration of alternative production media compared to the existing expensive ones. Herein, an effort has been made to utilize waste and cheaply available local resources including; waste (expired) orange juice (WOJ), sugarcane juice (SC) and coconut water (CW) as alternative media for BC production in comparison to the synthetic media (control). Methods: Waste and cheap resources were collected from the local market, screened filtered and optimized for the development of BC culture media. BC production from all media was observed under static cultivation for 10 days. The results indicated 2.75, 2.56, 3.32 and 1.68 g/L BC production that corresponded to 27.5%, 21.7 %, 20.1 % and 31.6 % sugar to BC conversion from control, WOJ, SC and CW media, respectively. Morphology and crystalline features of produced BC samples were observed through FE-SEM and XRD analysis. It was noteworthy that BC produced from all alternative sources indicated high water holding capabilities (WHC) and water retention time (WRT) that augment their applicability in drug delivery and wound healing applications. Conclusion: The BC production from cheap resources and its high physical, mechanical and biological properties can be of high interest for scaling up and commercialization of BC production processes. Furthermore, its liquidabsorbing capabilities and retention time can help in drug carrying and medical application.

Purpose: The purpose of the present study was to make a biocompatible agar based composite material via incorporation of appropriate additives within the agar matrix for potential applications in drug delivery and biomedical fields. Methodology: Agar based composites were prepared by the incorporation of magnetic iron oxide nano particles, graphite and sodium aluminum as additives in different proportions within the agar matrix by a simple thermophysico- mechanical method. The as prepared agar based composites were then characterized by different techniques i.e. FTIR, SEM, TGA, XRD and EDX analyses. The FTIR peaks confirmed the presence of each component in the agar composite. SEM images showed the uniform distribution of each component in the agar composite. TGA study showed the thermal stability range of different composite sheets. XRD pattern revealed the crystallinity and EDX analysis confirmed the elemental composition of the prepared composites. The prepared agar based composites were evaluated for antimicrobial activities against three pathogenic bacterial strains Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia and the result indicated efficient antimicrobial activities for all composites. Conclusion: From the overall study, it was concluded that due to the non-toxic nature, thermal stability and excellent antibacterial properties, the prepared agar based composites can receive potential biomedical applications.

Purpose: Leukemia, one of the major cancers, affects a large proportion of people around the world. Better treatment options for leukemia are required due to a large number of side effects associated with current therapeutic regimens. In the present study, we sought to determine the pathway of triggering apoptosis of leukemic cells by Ocimum basilicum (O. basilicum) plant extract. Materials/Methods: Methanolic extract of the O. basilicum plant material was prepared. The crude extract was fractionated into several fractions through column chromatography using ethyl acetate and n-hexane as eluting solvents. Cell viability of leukemic cells was assessed via Cell titer GLO assay and apoptosis was measured through Annexin V/PI staining. Two apoptotic molecules JNK and caspases were analyzed through western blotting while pro-inflammatory cytokines TNFα, CCL2 and CXCL8 using qPCR. Fractions were characterized through LC-MS. Results: The most potent with lowest IC50 values among the fractions were BF2 (2:8 n-hexane:ethyl acetate) and BF3 (3:7 n-hexane:ethyl acetate). Cytotoxicity was associated with apoptosis. Apoptosis was found caspasedependent and P-JNK activation was detected sustained. A significant increase in the level of TNF α and a decrease in the level of CXCL8 were observed in BF2 and BF3 treated cells. Conclusion: The fractions of O. basilicum extract were found to kill cells following JNK pathway activation. Excellent results were obtained with BF2 and BF3 probably due to predominant Epicatechin and Cinnamic acid derivatives in these fractions.

Background: Bacterial cellulose (BC) has recently attained greater interest in various research fields, including drug delivery for biomedical applications. BC has been studied in the field of drug delivery, such as tablet coating, controlled release systems and prodrug design. Objective: In the current work, we tested the feasibility of BC as a drug carrier in microparticulate form for potential pharmaceutical and biomedical applications. Methods: For this purpose, drug-loaded BC microparticles were prepared by simple grinding and injection moulding method through regeneration. Model drugs, i.e., cloxacillin (CLX) and cefuroxime (CEF) sodium salts were loaded in these microparticles to assess their drug loading and release properties. The prepared microparticles were evaluated in terms of particle shapes, drug loading efficiency, physical state of the loaded drug, drug release behaviour and antibacterial properties. Results: The BC microparticles were converted to partially amorphous state after regeneration. Moreover, the loaded drug was transformed into the amorphous state. The results of scanning electron microscopy (SEM) showed that microparticles had almost spherical shape with a size of ca. 350-400 μm. The microparticles treated with higher drug concentration (3%) exhibited higher drug loading. Keeping drug concertation constant, i.e., 1%, the regenerated BC (RBC) microparticles showed higher drug loading (i.e., 37.57±0.22% for CEF and 33.36±3.03% for CLX) as compared to as-synthesized BC (ABC) microparticles (i.e., 9.46±1.30% for CEF and 9.84±1.26% for CLX). All formulations showed immediate drug release, wherein more than 85% drug was released in the initial 30 min. Moreover, such microparticles exhibited good antibacterial activity with larger zones of inhibition for drug loaded RBC microparticles as compared to corresponding ABC microparticles. Conclusion: Drug loaded BC microparticles with immediate release behaviour and antibacterial activity were fabricated. Such functionalized microparticles may find potential biomedical and pharmaceutical applications.