Praveen Kumar Vemula

Silver-nanoparticle-embedded antimicrobial paints based on vegetable oil

Developing bactericidal coatings using simple green chemical methods could be a promising route to potential environmentally friendly applications. Here, we describe an environmentally friendly chemistry approach to synthesize metal-nanoparticle (MNP)-embedded paint, in a single step, from common household paint. The naturally occurring oxidative drying process in oils, involving free-radical exchange, was used as the fundamental mechanism for reducing metal salts and dispersing MNPs in the oil media, without the use of any external reducing or stabilizing agents. These well-dispersed MNP-in-oil dispersions can be used directly, akin to commercially available paints, on nearly all kinds of surface such as wood, glass, steel and different polymers. The surfaces coated with silver-nanoparticle paint showed excellent antimicrobial properties by killing both Gram-positive human pathogens (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli). The process we have developed here is quite general and can be applied in the synthesis of a variety of MNP-in-oil systems.

Engineered cell homing

One of the greatest challenges in cell therapy is to minimally invasively deliver a large quantity of viable cells to a tissue of interest with high engraftment efficiency. Low and inefficient homing of systemically delivered mesenchymal stem cells (MSCs), for example, is thought to be a major limitation of existing MSC-based therapeutic approaches, caused predominantly by inadequate expression of cell surface adhesion receptors. Using a platform approach that preserves the MSC phenotype and does not require genetic manipulation, we modified the surface of MSCs with a nanometer-scale polymer construct containing sialyl Lewis(x) (sLe(x)) that is found on the surface of leukocytes and mediates cell rolling within inflamed tissue. The sLe(x) engineered MSCs exhibited a robust rolling response on inflamed endothelium in vivo and homed to inflamed tissue with higher efficiency compared with native MSCs. The modular approach described herein offers a simple method to potentially target any cell type to specific tissues via the circulation.

Self-assembled prodrugs: an enzymatically triggered drug-delivery platform.

Enzyme catalysis as a tool to disassemble supramolecular hydrogels to control the release of encapsulated drugs provides an opportunity to design a wide range of enzyme-specific low-molecular-weight hydrogelators. In this proof-of-concept work, we report the synthesis of low-molecular-weight amphiphilic prodrugs as hydrogelators from a well-known drug acetaminophen (which belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers)). We have shown the ability of prodrugs to self-assemble to form hydrogels that could subsequently encapsulate a second drug such as curcumin, which is a known chemopreventive and anti-inflammatory hydrophobic drug. Upon enzyme-triggered degradation, the hydrogel released single or multiple drugs at physiologically simulated conditions in vitro. Given that the degradation products consist of the drug and a fatty acid, this approach has an advantage over polymer-based prodrugs that generate polymer fragments with heterogeneous chain lengths upon degradation that may present complex toxicity profiles. Additionally, drug-release occurred without burst release. Spectrophotometric experiments supported the drug-release, and the rate was controlled by modulation of temperature and enzyme concentration. Mesenchymal stem cells treated with prodrugs retained their stem cell properties including the capacity of multi-lineage differentiation, and maintained their adhesive and proliferation capacities with high viability. The present biomaterials could have broad applications as drug-delivery vehicles and cell invasive matrices.

Tracking mesenchymal stem cells with iron oxide nanoparticle loaded poly(lactide-co-glycolide) microparticles.

Monitoring the location, distribution and long-term engraftment of administered cells is critical for demonstrating the success of a cell therapy. Among available imaging-based cell tracking tools, magnetic resonance imaging (MRI) is advantageous due to its noninvasiveness, deep penetration, and high spatial resolution. While tracking cells in preclinical models via internalized MRI contrast agents (iron oxide nanoparticles, IO-NPs) is a widely used method, IO-NPs suffer from low iron content per particle, low uptake in nonphagocytotic cell types (e.g., mesenchymal stem cells, MSCs), weak negative contrast, and decreased MRI signal due to cell proliferation and cellular exocytosis. Herein, we demonstrate that internalization of IO-NP (10 nm) loaded biodegradable poly(lactide-co-glycolide) microparticles (IO/PLGA-MPs, 0.4-3 μm) in MSCs enhances MR parameters such as the r(2) relaxivity (5-fold), residence time inside the cells (3-fold) and R(2) signal (2-fold) compared to IO-NPs alone. Intriguingly, in vitro and in vivo experiments demonstrate that internalization of IO/PLGA-MPs in MSCs does not compromise inherent cell properties such as viability, proliferation, migration and their ability to home to sites of inflammation.

Biorefinery: A Design Tool for Molecular Gelators

Molecular gels, the macroscopic products of a nanoscale bottom-up strategy, have emerged as a promising functional soft material. The prospects of tailoring the architecture of gelator molecules have led to the formation of unique, highly tunable gels for a wide spectrum of applications from medicine to electronics. Biorefinery is a concept that integrates the processes of converting biomass/renewable feedstock and the associated infrastructure used to produce chemicals and materials, which is analogous to petroleum-based refinery. The current review assimilates the successful efforts to demonstrate the prospects of the biorefinery concept for developing new amphiphiles as molecular gelators. Amphiphiles based on naturally available raw materials such as amygdalin, vitamin C, cardanol, arjunolic acid, and trehalose that possess specific functionality were synthesized using biocatalysis and/or chemical synthesis. The hydrogels and organogels obtained from such amphiphiles were conceptually demonstrated for diverse applications including drug-delivery systems and the templated synthesis of hybrid materials.

Chemical Engineering of Mesenchymal Stem Cells to Induce a Cell Rolling Response

Covalently conjugated sialyl Lewis X (SLeX) on the mesenchymal stem cell (MSC) surface through a biotin-streptavidin bridge imparts leukocyte-like rolling characteristics without altering the cell phenotype and the multilineage differentiation potential. We demonstrate that the conjugation of SLeX on the MSC surface is stable, versatile, and induces a robust rolling response on P-selectin coated substrates. These results indicate the potential to increase the targeting efficiency of any cell type to specific tissue.

Design and development of soft nanomaterials from biobased amphiphiles

Design and development of different forms of soft matter from renewable (biomass) feedstocks is gaining attention in current research. This highlight summarizes our continuing efforts towards the effective utilization of renewable resources for new chemicals, fuels and soft materials, and selected successful stories in that direction. Cashew nut shell liquid, an industrial by-product, was used as a raw material to synthesize aryl glycolipids which upon self-assembly generated an array of soft materials such as lipid nanotubes, twisted/helical nanofibers, low-molecular-weight hydro/organogels and liquid crystals. These soft architectures were fully characterized by using different techniques. In another example, amygdalin, a by-product of the apricot industry, was used to develop novel amphiphiles, which showed unprecedented gelation properties in a wide range of solvents. To take these soft nanomaterials to a second level, we successfully demonstrated the utility of these hydrogels as drug delivery vehicles. Intriguingly, enzyme catalysis was used as a tool to make and break the hydrogels, which apparently triggered controlled drug delivery. We believe these results and this highlight will motivate us and others in the field of biobased materials research, green chemistry and soft material development through self-assembly processes, to design and develop new functional materials from plant/crop-based renewable resources, otherwise underutilized.

An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease.

A hydrogel binds to inflamed tissues, delivering therapeutics locally and reducing systemic drug exposure in mouse models of inflammatory bowel disease. Charged gels cozy up to inflamed tissues Inflammation is a driving factor of many chronic diseases, such as inflammatory bowel disease (IBD). To get potent drugs right to the site of inflammation, Zhang et al. designed a negatively charged hydrogel that could self-assemble and deliver hydrophobic anti-inflammatory drugs directly to the inflamed colon surface, which is positively charged. Dexamethasone-loaded hydrogels were administered as an enema to a genetic mouse model of ulcerative colitis (UC)—a type of IBD. The hydrogels relieved inflammation in the animals more effectively than did the free drug, which runs the risk of also affecting healthy tissues. In tissue samples from patients with UC and in another chemically induced mouse model of colitis, the hydrogel microfibers preferentially stuck to the inflamed regions. These findings together suggest that this new gel-based delivery system could reach and directly treat areas of epithelial inflammation in humans. There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD.

Recent developments in β-C-glycosides: synthesis and applications.

In the last few years, considerable progress has been made in the synthesis of C-glycosides. Despite its challenging chemistry, due to its versatility, C-glycosides play a pivotal role in developing novel materials, surfactants and bioactive molecules. In this review, we present snapshots of various synthetic methodologies developed for C-glycosides in the recent years and the potential application of C-glycosides derived from β-C-glycosidic ketones.

Prodrugs as self-assembled hydrogels: a new paradigm for biomaterials.

Prodrug-based self-assembled hydrogels represent a new class of active biomaterials that can be harnessed for medical applications, in particular the design of stimuli responsive drug delivery devices. In this approach, a promoiety is chemically conjugated to a known-drug to generate an amphiphilic prodrug that is capable of forming self-assembled hydrogels. Prodrug-based self-assembled hydrogels are advantageous as they alter the solubility of the drug, enhance drug loading, and eliminate the use of harmful excipients. In addition, self-assembled prodrug hydrogels can be designed to undergo controlled drug release or tailored degradation in response to biological cues. Herein we review the development of prodrug-based self-assembled hydrogels as an emerging class of biomaterials that overcome several common limitations encountered in conventional drug delivery.