Polymeric Networks Containing Amine Derivatives as Organocatalysts for Knoevenagel Reaction within Continuously Driven Microfluidic Reactors.

The Knoevenagel reaction is a classic reaction in organic chemistry for the formation of C-C bonds. In this study, various catalytic monomers for Knoevenagel reactions were synthesized and polymerized via photolithography to form polymeric gel dots with a composition of 90% catalyst, 9% gelling agent and 1% crosslinker. Furthermore, these gel dots were inserted into a microfluidic reactor (MFR) and the conversion of the reaction using gel dots as catalysts in the MFR for 8 h at room temperature was studied. The gel dots containing primary amines showed a better conversion of about 83-90% with aliphatic aldehyde and 86-100% with aromatic aldehyde, compared to the tertiary amines (52-59% with aliphatic aldehyde and 77-93% with aromatic aldehydes) which resembles the reactivity of the amines. Moreover, the addition of polar solvent (water) in the reaction mixture and the swelling properties of the gel dots by altering the polymer backbone showed a significant enhancement in the conversion of the reaction, due to the increased accessibility of the catalytic sites in the polymeric network. These results suggested the primary-amine-based catalysts facilitate better conversion compared to tertiary amines and the reaction solvent had a significant influence on organocatalysis to improve the efficiency of MFR.

Combinatorial therapy using RNAi and curcumin nano-architectures regresses tumors in breast and colon cancer models.

Cancer is a debilitating disease and one of the leading causes of death in the world. In spite of the current clinical management being dependent on applying robust pathological variables and well-defined therapeutic strategies, there is an imminent need for novel and targeted therapies with least side effects. RNA interference (RNAi) has gained attention due to its precise potential for targeting multiple genes involved in cancer progression. Nanoparticles with their enhanced permeability and retention (EPR) effect have been found to overcome the limitations of RNAi-based therapies. With their high transportation capacity, nanocarriers can target RNAi molecules to tumor tissues and protect them from enzymatic degradation. Accumulating evidence has shown that tyrosine kinase Ephb4 is overexpressed in various cancers. Therefore, we report here the development and pre-clinical validation of curcumin-chitosan-loaded: eudragit-coated nanocomposites conjugated with Ephb4 shRNA as a feasible bio-drug to suppress breast and colon cancers. The proposed bio-drug is non-toxic and bio-compatible with a higher uptake efficiency and through our experimental results we have demonstrated the effective site-specific delivery of this biodrug and the successfull silencing of their respective target genes in vivo in autochthonous knockout models of breast and colon cancer. While mammary tumors showed a considerable decrease in size, oral administration of the biodrug conjugate to Apc knockout colon models prolonged the animal survival period by six months. Hence, this study has provided empirical proof that the combinatorial approach involving RNA interference and nanotechnology is a promising alliance for next-generation cancer therapeutics.

PEGylated ethyl cellulose micelles as a nanocarrier for drug delivery.

Natural polymers provide a better alternative to synthetic polymers in the domain of drug delivery systems (DDSs) because of their renewability, biocompatibility, and low immunogenicity; therefore, they are being studied for the development of bulk/nanoformulations. Likewise, current methods for engineering natural polymers into micelles are in their infancy, and in-depth studies are required using natural polymers as controlled DDSs. Accordingly, in our present study, a new micellar DDS was synthesized using ethyl cellulose (EC) grafted with polyethylene glycol (PEG); it was characterized, its properties, cell toxicity, and hemocompatibility were evaluated, and its drug release kinetics were demonstrated using doxorubicin (DOX) as a model drug. Briefly, EC was grafted with PEG to form the amphiphilic copolymers EC-PEG1 and EC-PEG2 with varying PEG concentrations, and nano-micelles were prepared with and without the drug (DOX) via a dialysis method; the critical micelle concentrations (CMCs) were recorded to be 0.03 mg mL-1 and 0.00193 mg mL-1 for EC-PEG1 and EC-PEG2, respectively. The physicochemical properties of the respective nano-micelles were evaluated via various characterization techniques. The morphologies of the nano-micelles were analyzed via transmission electron microscopy (TEM), and the average size of the nano-micelles was recorded to be ∼80 nm. In vitro, drug release studies were done for 48 h, where 100% DOX release was recorded at pH 5.5 and 52% DOX release was recorded at pH 7.4 from the micelles. In addition, cytotoxicity studies suggested that DOX-loaded micelles were potent in killing MDA-MB-231 and MCF-7 cancer cells, and the blank micelles were non-toxic toward cancerous and normal cells. A cellular uptake study via fluorescence microscopy indicated the internalization of DOX-loaded micelles by cancer cells, delivering the DOX into the cellular compartments. Based on these studies, we concluded that the developed material should be studied further via in vivo studies to understand its potential as a controlled DDS to treat cancer.

Blends of neem oil based polyesteramide as nanofiber mats to control Culicidae.

Mosquitoes act as vectors for several disease-causing microorganisms and pose a threat to mankind by transmitting various diseases. There are different conventional methods to repel or kill these mosquitoes for avoiding susceptibility against infections. However, to overcome the difficulties with conventional methods, new advanced materials are being studied. For the first time, we report developing a nanofiber mat with a controlled release of insecticide to repel or detain the mosquitoes. Briefly, various blend compositions were prepared by manipulating the ratio of neem oil-based polyesteramide (PEA) and polycaprolactone (PCL) immobilized with insecticide, transfluthrin (Tf). The blend solutions were electrospun to get non-woven nanofiber mats, and these nanomaterials were characterized by various spectroscopic techniques to understand their physicochemical properties. The surface morphology was analyzed using environmental scanning electron microscopy (E-SEM), and the diameter of the nanofibers was in the range of 200 to 450 nm. Further, thermal and mechanical properties were evaluated to understand the stability of nanofiber mats. In vitro drug release studies of nanofiber mat PPT-1335 showed controlled and sustained release of Tf, with ∼35% of Tf released in 24 h. However, a film of the same composition (PPT-1335) showed ∼5% of Tf release within 24 h. Moreover, in vivo bio-efficacy studies suggested the mortality of mosquitoes was about 50% with PP-133, which was further increased to 100% within 12 h in the presence of Tf (PPT-1335). However, 60% mortality of mosquitoes was observed with the film of PPT-1335. Hence, the nanofiber mat showed better efficacy against mosquitoes as compared to the film of the same composition. The degradation studies under various conditions revealed biocompatibility of the developed nanofiber mats with the ecosystem.

Polyesteramide of Neem Oil and Its Blends as an Active Nanomaterial for Tissue Regeneration.

Neem oil gained importance due to its antibacterial properties. Therefore, it is extensively being used for various applications. Oils can be polymerized as a polyesteramide to extend their utility as biomaterials. In our studies, we synthesized polyesteramide from neem oil and various compositions of blends were prepared with the drug, chlorohexidine digluconate (CH) to develop a nanomaterial for tissue regeneration. The studies such as cytotoxicity, biodegradable, antibacterial, in vitro drug release, in vivo wound healing, and histopathological studies were performed to identify their potential for tissue regeneration. In vivo wound healing studies of the nanofiber mats with and without CH recorded a faster healing rate as compared to the commercial cream (povidone-iodine). Most importantly, there was no requirement of repeated application of nanofiber mats during the treatment. The histopathology studies also suggested the re-epithelialization of the wounds. Hence, these nanomaterials are considered to be environmentally safe scaffolds for efficient tissue regeneration applications.

Polyhydroxyalkanoates as biomaterials.

Polyhydroxyalkanoates (PHAs) are biopolymers synthesized by bacteria under unbalanced growth conditions. These biopolymers are considered as potential biomaterials for future applications because they are biocompatible, biodegradable, and easy to produce and functionalize with strong mechanical strength. Currently, PHAs are being extensively innovated for biomedical applications due to their prerequisite properties. The wide range of biomedical applications includes drug delivery systems, implants, tissue engineering, scaffolds, artificial organ constructs, etc. In this article we review the utility of PHAs in various forms (bulk/nano) for biomedical applications so as to bring about the future vision for PHAs as biomaterials for the advancement of research and technology.