TY - JOUR T1 - iRGD conjugated nimbolide liposomes protect against endotoxin induced acute respiratory distress syndrome. JF - Nanomedicine Y1 - 2021 A1 - Pooladanda, Venkatesh A1 - Thatikonda, Sowjanya A1 - Sunnapu, Omprakash A1 - Tiwary, Shristy A1 - Vemula, Praveen Kumar A1 - Talluri, M V N Kumar A1 - Godugu, Chandraiah AB -

Acute respiratory distress syndrome (ARDS) is a deadly respiratory illness associated with refractory hypoxemia and pulmonary edema. The recent pandemic outbreak of COVID-19 is associated with severe pneumonia and inflammatory cytokine storm in the lungs. The anti-inflammatory phytomedicine nimbolide (NIM) may not be feasible for clinical translation due to poor pharmacokinetic properties and lack of suitable delivery systems. To overcome these barriers, we have developed nimbolide liposomes conjugated with iRGD peptide (iRGD-NIMLip) for targeting lung inflammation. It was observed that iRGD-NIMLip treatment significantly inhibited oxidative stress and cytokine storm compared to nimbolide free-drug (f-NIM), nimbolide liposomes (NIMLip), and exhibited superior activity compared to dexamethasone (DEX). iRGD-NIMLip abrogated the LPS induced p65 NF-κB, Akt, MAPK, Integrin β3 and β5, STAT3, and DNMT1 expression. Collectively, our results demonstrate that iRGD-NIMLip could be a promising novel drug delivery system to target severe pathological consequences observed in ARDS and COVID-19 associated cytokine storm.

VL - 33 ER - TY - JOUR T1 - Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art and future perspectives. JF - Adv Drug Deliv Rev Y1 - 2018 A1 - Kotla, Niranjan G A1 - Rana, Shubhasmin A1 - Sivaraman, Gandhi A1 - Sunnapu, Omprakash A1 - Vemula, Praveen K A1 - Pandit, Abhay A1 - Rochev, Yury AB -

Oral colon-specific delivery systems emerged as the main therapeutic cargos by making a significant impact in the field of modern medicine for local drug delivery in intestinal inflammation. The site-specific delivery of therapeutics (aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can provide prominent advantages in mucosal healing (MH). Attaining gut mucosal healing and anti-fibrosis are main treatment outcomes in inflammatory bowel disease (IBD). The pharmaceutical strategies that are commonly used to achieve a colon-specific drug delivery system include time, pH-dependent polymer coating, prodrug, colonic microbiota-activated delivery systems and a combination of these approaches. Amongst the different approaches reported, the use of biodegradable polysaccharide coated systems holds great promise in delivering drugs to the ulcerative regions. The present review focuses on major physiological gastro-intestinal tract challenges involved in altering the pharmacokinetics of delivery systems, pathophysiology of MH and fibrosis, reported drug-polysaccharide cargos and focusing on conventional to advanced disease responsive delivery strategies, highlighting their limitations and future perspectives in intestinal inflammation therapy.

ER - TY - JOUR T1 - Prevention of pesticide-induced neuronal dysfunction and mortality with nucleophilic poly-Oxime topical gel. JF - Sci Adv Y1 - 2018 A1 - Thorat, Ketan A1 - Pandey, Subhashini A1 - Chandrashekharappa, Sandeep A1 - Vavilthota, Nikitha A1 - Hiwale, Ankita A A1 - Shah, Purna A1 - Sreekumar, Sneha A1 - Upadhyay, Shubhangi A1 - Phuntsok, Tenzin A1 - Mahato, Manohar A1 - Mudnakudu-Nagaraju, Kiran K A1 - Sunnapu, Omprakash A1 - Vemula, Praveen K AB -

Organophosphate-based pesticides inhibit acetylcholinesterase (AChE), which plays a pivotal role in neuromuscular function. While spraying in the field, farmworkers get exposed to pesticides through the dermal route. Internalized pesticide inhibits AChE, which leads to neurotoxicity, cardiotoxicity, cognitive dysfunction, loss of endurance, and death in severe cases. Here, we present a nucleophilic pyridine-2-aldoxime-functionalized chitosan-based topical gel (-Oxime gel) that rapidly deactivates organophosphates, methyl parathion (MPT), on the skin of rats, which leads to reduced AChE inhibition in the blood and tissues. Testing the robustness of -Oxime gel, we report reduction in AChE inhibition following repeated dermal administration of MPT in the presence of -Oxime gel. Furthermore, -Oxime gel prevented MPT-induced neuromuscular dysfunction, loss of endurance, and locomotor coordination. We observe a 100% survival in rats following topical MPT administration in the presence of -Oxime gel. This prophylactic gel may therefore help farmworkers by limiting pesticide-induced toxicity and mortality.

VL - 4 IS - 10 ER - TY - JOUR T1 - Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl{,} di-hydroxy ethylammonium chloride based cationic amphiphiles JF - RSC Adv. Y1 - 2017 A1 - Hiwale, Ankita A. A1 - Voshavar, Chandrashekhar A1 - Dharmalingam, Priya A1 - Dhayani, Ashish A1 - Mukthavaram, Rajesh A1 - Nadella, Rasajna A1 - Sunnapu, Omprakash A1 - Gandhi, Sivaraman A1 - Naidu, V. G. M. A1 - Chaudhuri, Arabinda A1 - Marepally, Srujan A1 - Vemula, Praveen Kumar AB -

The success of gene therapy critically depends on the availability of efficient transfection vectors. Cationic lipids are the most widely studied non-viral vectors. The molecular architecture of the cationic lipid determines its transfection efficiency. Variations in alkyl chain lengths of lipids influence self-assembly and liposomal fusion with the cell membrane. These factors determine the transfection ability of the lipid. Thus{,} to probe the effect of asymmetry in hydrophobic chains on transfection efficiency{,} we designed and synthesized a series of cationic lipids by systematically varying one of the two alkyl chains linked to the quaternary nitrogen centre from C18 to C10 and keeping the other alkyl C18 chain constant (Lip1818-Lip1810). Transfection studies in multiple cultured mammalian cells (CHO{,} B16F10 and HeLa) revealed that the lipids with C18:C14 and C18:C12 alkyl chains (Lip1814 & Lip1812) showed 20-30% higher transfection efficacies than their counterparts at 2 : 1 and 4 : 1 lipid to pDNA charge ratios. Cryo-transmission electron images showed unilamellar vesicle structures for the liposomes of lipids. Mechanistic studies involving Small Angle X-ray Scattering (SAXS) revealed that asymmetry in the hydrophobic region has a significant impact on liposomal fusion with the plasma membrane model. Collectively{,} these findings demonstrate that chain length asymmetry in the hydrophobic region of cationic lipids has an important role in their liposome-DNA interactions at optimal 2 : 1 and 4 : 1 lipid to pDNA charge ratios{,} which in turn modulates their gene transfer properties.

VL - 7 UR - http://dx.doi.org/10.1039/C7RA02271A ER -