Continuous flow catalysis utilizing gel-bound organocatalysts within a microfluidic reactor represents a compelling strategy in the realm of organic synthesis. In this study, a quinuclidine-based catalytic monomer (QMA) was synthesized to create polymer gel dots through the process of photopolymerization that serve as a support for the catalyst. The resulting gel-bound organocatalysts were assembled within a continuous microfluidic reactor to facilitate the Baylis-Hillman reaction between various aldehydes and acrylonitrile at a temperature of 50 °C. The conversion of the product was assessed using 1H NMR spectroscopy as an offline analytical method over a duration of 8 h. The findings indicated that highly reactive aldehydes achieved conversion rates exceeding 90%, in contrast to their less reactive counterparts. Furthermore, these results were juxtaposed with previously published data derived from alternative synthetic methodologies, revealing that the continuous microfluidic reactions employing integrated organocatalysts within polymer networks exhibited significantly higher conversions with reduced reaction times (8 h) at the same temperature (50 °C). Additionally, the influence of different geometries (round, triangular, and square) of the gel dots on catalytic activity was investigated, with round and square gel dots demonstrating slightly superior performance compared with triangular gel dots, attributed to their increased surface area. Moreover, an extended reaction period of 6 days was conducted using 4-bromobenzaldehyde and acrylonitrile, resulting in a conversion rate exceeding 70%, which remained stable for 5 days before experiencing a slight decline due to product accumulation on the gel dots.

The development of sustainable catalysts is the main objective in green chemistry approaches. In this study, a catalytically active polymer based on a tertiary amine was synthesized, functionalized with a photo-crosslinker, and structured into nanofibers via electrospinning technique with polycaprolactone (PCL) as a stabilizing additive. Subsequent photo-crosslinking yielded hierarchically porous polymers with high swelling properties and increased surface areas, thereby improving the accessibility of the immobilized catalytically active sites. The nanofiber mats were incorporated into a microfluidic reactor (MFR) setup and utilized as heterogeneous catalysts for the Knoevenagel reaction of malononitrile with different aldehydes. It was observed that the system demonstrated a substantial improvement in NMR yields (40-60%) and turnover frequencies (50-80 h-1) in comparison to catalytical systems that had been previously published. Reusability studies showed reproducibility of NMR yields over up to three cycles. The obtained results demonstrate the potential of electrospun, photo-crosslinked nanofibers as efficient heterogeneous catalysts in microfluidic synthesis, thus contributing to more sustainable production of valuable malononitrile derivatives.

The use of organo-catalysis in continuous-flow reactor systems is gaining attention in medicinal chemistry due to its cost-effectiveness and reduced chemical waste. In this study, bioactive curcumin (CUM) derivatives were synthesized in a continuously operated microfluidic reactor (MFR), using piperidine-based polymeric networks as catalysts. Piperidine methacrylate and piperidine acrylate were synthesized and subsequently copolymerized with complementary monomers (MMA or DMAA) and crosslinkers (EGDMA or MBAM) via photopolymerization, yielding different polymeric networks. Initially, batch reactions were optimized for the organo-catalytic Knoevenagel condensation between CUM and 4-nitrobenzaldehyde, under various conditions, in the presence of polymer networks. Conversion was assessed using offline 1H NMR spectroscopy, revealing an increase in conversion with enhanced swelling properties of the polymer networks, which facilitated greater accessibility of catalytic sites. In continuous-flow MFR experiments, optimized polymer gel dots exhibited superior catalytic performance, achieving a conversion of up to 72%, compared to other compositions. This improvement was attributed to the enhanced swelling in the reaction mixture (DMSO/methanol, 7:3 v/v) at 40 °C over 72 h. Furthermore, the MFR system enabled the efficient synthesis of a series of CUM derivatives, demonstrating significantly higher conversion rates than traditional batch reactions. Notably, while batch reactions required 90% catalyst loading in the gel, the MFR system achieved a comparable or superior performance with only 50% catalyst, resulting in a higher turnover number. These findings underscore the advantages of continuous-flow organo-catalysis in enhancing catalytic efficiency and sustainability in organic synthesis.

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.

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.

A hybrid of poly-l-lactic acid (PLA) and poly-epsilon-caprolactone (PCL) system was designed using hydrophilic generally regarded as safe (GRAS) protein, egg albumin (EA), and fabricated as nanofiber mats (NM) to facilitate improved cell interactions and functionality. Our studies include, preparation and analysis of physicochemical properties of NM. Surface morphology of NM was smooth with the diameter ranging from 250 to 400 nm. The contact angle of NM decreased from 80 to 45 degrees with the increase in EA concentration. The rate and extent of swelling was increased 3-folds with the addition of EA. Release studies of NM showed maximum amount of MTz was released with the increase in MTz concentration (>85%). The MTz interaction with EA and structure stability of EA was confirmed from fluorescence and circular dichroism studies. NM showed increase in inhibition of bacterial growth of Staphylococcus aureus and Escherichia coli with the increase in MTz concentration. Cell viability of the NM was >80% and also, the cell proliferation increased as EA content increased. NM hemolytic activity was less than 5% suggesting compatibility. Hence, results concluded that EA had regulated hydrophobicity, promoted cell interactions, and proliferation and therefore, NM is considered safe for tissue regeneration.

Landfilling of rotten tomatoes can lead to environmental instability and a huge economic loss to the producers. This letter reports an effective valorization of tomato waste into a promising biopolymer, i.e., poly-gamma-glutamic acid (gamma-PGA) by a novel biocatalyst Bacillus paralicheniformis NCIM 5769. The gamma-PGA is one of the most expensive biopolymers with multifarious applications in wound healing, drug delivery, and regenerative medicine fields. However, its adoption into various applications is finite due to its exorbitant production cost. Herein, rotten tomatoes (without additional nutrient supplementation) served as the chassis for the fermentative production of 40 g/L of highly pure gamma-PGA within 48 h at ambient temperature. Further, NMR, DSC, and TGA confirmed the purity of synthesized gamma-PGA identical to standard gamma-PGA. This process has potential in the commercialization of.-PGA by significantly reducing the production cost, followed by the effective utilization of tomato waste leading to United Nations Sustainable Development Goal 12 (i.e., ensure sustainable consumption and production patterns).

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.

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.

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 reepithelialization of the wounds. Hence, these nanomaterials are considered to be environmentally safe scaffolds for efficient tissue regeneration applications.

Correction for ‘Polyhydroxyalkanoates as biomaterials’ by Bhagyashri S. Thorat Gadgil et al., Med. Chem. Commun., 2017, 8, 1774–1787.

In this chapter we bring in the collective information about intravenous and transdermal nano drug delivery systems (DDSs), which include different kinds of constituents used for the design of nano DDSs, their various forms, methods, and characterization of nanoformulations.

Correction for 'Polyhydroxyalkanoates as biomaterials' by Bhagyashri S. Thorat Gadgil et al., Med. Chem. Commun., 2017, 8, 1774-1787.

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.

New nanomaterials of bio-origin with improved mechanical properties are in demand for biomedical application. Therefore, we propose to design and fabricate bioactive nano-matrices with good mechanical strength using polyesteramides derived from linseed oil. Polyesteramide was synthesized from linseed oil and blended with poly(L-lactide) and human serum albumin to enhance the mechanical strength, biodegradation, biocompatibility and hydrophilicity. The various blend solutions with and without drugs (triclosan and metronidazole) were electrospun into non-woven nano-matrices. The morphology of the nano-matrices represented smooth and fine nanofibers with the diameter ranging from 300 to 400 nm. Drug binding efficiency, cytotoxicity, hydrophilicity, thermal and mechanical studies indicated their suitability as biomaterials. To demonstrate their utility, the drug release kinetics and antibacterial properties were evaluated. The metronidazole loaded nano-matrices showed drug release up to 8 h, beyond which no release was observed until 72 h. Antibacterial studies were done using the drugs triclosan and metronidazole. The antibacterial activity of the drug loaded nanofiber mats increased with the increase in drug concentration. The uniqueness of the developed nano-matrices of polyesteramide blends is that their mechanical strength is 3-fold higher than that of the nano-matrices of poly(L-lactide), which is one of the essential features of these nano-matrices to be used as a biomaterial for biomedical applications.

Chapter 2 Polyhydroxyalkanoates: The Application of Eco-Friendly Materials G.V.N. Rathna, G.V.N. Rathna rv.gundloori@ncl.res.in Polymer Science and Engineering, CSIR- National Chemical Laboratory, Pune, IndiaSearch for more papers by this authorBhagyashri S. Thorat Gadgil, Bhagyashri S. Thorat Gadgil Polymer Science and Engineering, CSIR- National Chemical Laboratory, Pune, IndiaSearch for more papers by this authorNaresh Killi, Naresh Killi Polymer Science and Engineering, CSIR- National Chemical Laboratory, Pune, IndiaSearch for more papers by this author G.V.N. Rathna, G.V.N. Rathna rv.gundloori@ncl.res.in Polymer Science and Engineering, CSIR- National Chemical Laboratory, Pune, IndiaSearch for more papers by this authorBhagyashri S. Thorat Gadgil, Bhagyashri S. Thorat Gadgil Polymer Science and Engineering, CSIR- National Chemical Laboratory, Pune, IndiaSearch for more papers by this authorNaresh Killi, Naresh Killi Polymer Science and Engineering, CSIR- National Chemical Laboratory, Pune, IndiaSearch for more papers by this author Book Editor(s):Susheel Kalia, Susheel KaliaSearch for more papers by this authorLuc Avérous, Luc AvérousSearch for more papers by this author First published: 05 February 2016 https://doi.org/10.1002/9781119117360.ch2Citations: 1 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onFacebookTwitterLinked InRedditWechat Summary This chapter contains sections titled: Introduction Natural Occurrence Bio-Synthetic/Semi-Synthetic Approach Environmental Aspects Applications Biomedical Applications Biodegradable Packaging Material Agriculture Other Applications Scope of PHAs Conclusions Acknowledgments Citing Literature Biodegradable and Biobased Polymers for Environmental and Biomedical Applications RelatedInformation

Oligomers of curcumin acrylates were blended with polylactide and electrospun to nanofiber mats, which were antibacterial and highly porous.