Browsing by Author "Ruchi Chawla"

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Comparative evaluation of two intranasal forms of Curcumin: Quantitation and impact on mouse model of asthma
(Elsevier B.V., 2023) Payal Singh; Ruchi Chawla; Ajai Kumar Pandey; J.K. Mishra; Rashmi Singh
Aim of the study: Present study aimed to investigate impact of two different intranasal forms of curcumin on mouse model of asthma and detection of its absorption after different time points of administration. Since the systemic bioavailability of curcumin is very low, therefore, intranasal route of administration has been explored here where systemic absorption of two intranasal forms of curcumin was evaluated. Materials and methods: To explore the possibilities of its absorption and role in amelioration of asthma, two intranasal forms of curcumin, nasal drop and aerosol were administered to control and asthmatic mice. Blood plasma and lungs were collected at different time points of curcumin administration. Separation was done by using isocratic reversed phase high performance liquid chromatography (HPLC). Airway inflammation and oxidative stress parameters like SOD, Catalase, ROS, lipid peroxidation, and total inflammatory cell recruitments were analyzed to study efficacy of two intranasal forms of curcumin. Results: Maximum absorption was noted at 3 hrs of different intranasal forms of curcumin, administration, i.e., nasal drop (1.93 ± 0.050 plasma, 2.87 ± 0.26 in lungs) and aerosol form of curcumin where better absorption was noted in aerosol form as compared to nasal drop (Lungs 3.08 ± 0.12 aerosol, 2.05 ± 0.020 nasal drop) at 1 h. Both, curcumin aerosol and nasal drops were effective in ameliorating oxidative stress (p < 0.05) associated with asthma in mice model. The present study may pave the way towards the development of intranasal curcumin as complementary medication because of its better absorption in plasma and lungs. © 2023 The Author(s)
Crafting a Molecular Trojan Horse: Sialic Acid-Modified PLGA Nanoparticles for Targeted Lung Cancer Therapy
(American Chemical Society, 2025) Krishan Kumar; Manjit Saini; Varsha Rani; Mohini Mishra; None Priya; None Jatin; Siddharth Tiwari; Brahmeshwar Mishra; Ruchi Chawla
The glycan receptors prominently expressed on the surface of lung cancer cells offers promising targets for drug delivery. The prepared gemcitabine (GB)-loaded PLGA-NPs and sialic acid (Siac)-modified PLGA-NPs exhibited a uniform polydispersity index (PDI) value below 0.3, a particle size under 200 nm, and negative zeta potentials ranging from −17.45 to −21.45 mV. Entrapment efficiency (% EE) and drug loading values exceeded 70% and 8%, respectively. SEM and TEM showed that the particles were uniformly dispersed with a spherical shape. FTIR, XRD, TGA, and DSC analyses indicated the physiochemical stability of the drug within the nanoformulations. Controlled (26.92 to 31.64% within 24 h at pH 7.4) and pH-sensitive (36.80 to 40.25% within 24 h at pH 5.5) GB release were observed for the different formulations of PLGA-NPs. The MTT cytotoxicity assay revealed IC50 values for the GB control, GB-PLGA-NPs, and GB-PLGA-Siac-NPs as 13.65 ± 1.20, 8.14 ± 1.24, and 4.16 ± 1.05 μg/mL, respectively. The Co6-GB-PLGA-Siac-NPs showed significantly higher cellular uptake than that of the Co6-GB control (p < 0.001) and Co6-GB-PLGA-NPs (p < 0.01) respectively. Pharmacokinetic profiles indicated higher AUC values (ng·h/mL) for GB-PLGA-Siac-NPs (8355.07 ± 2006.45) compared to GB-PLGA-NPs (6145.58 ± 969.25) and the GB control (1510.72 ± 81.08), resulting in higher bioavailability of GB-PLGA-Siac-NPs. Biodistribution studies confirmed superior localization of DiD-GB-PLGA-Siac-NPs, indicated by radiant efficiency signal on B[a]P induced lung cancerous tissues relative to DiD-GB-PLGA-NPs after 1 h (p < 0.001), 4 h (p < 0.01), and 12 h (p < 0.001), which could be attributed to their ability to target glycans. In vivo anticancer efficacy in a B[a]P-induced lung cancer mice model depicted that GB-PLGA-Siac-NPs effectively inhibited lung cancer cells and reduced systemic toxicity, as evidenced by the average number of lung cancer cells, body weight values, survival analysis, biochemical parameters associated with organs (such as the liver and kidney), and histopathological analysis. Therefore, GB-loaded Siac-coated PLGA nanoparticles could serve as an efficient vehicle for GB delivery via targeting glycan receptors in lung cancer therapy. © 2025 American Chemical Society.
Design, fabrication, optimization and characterization of memantine-loaded biodegradable PLGA nanoscaffolds for treatment of Alzheimer’s disease
(Institute of Physics, 2022) Varsha Rani; Ruchi Chawla
This study aimed to design and develop nanoscaffolds for the controlled release of memantine by non-solvent-induced phase separation (N-TIPS) method. The development and optimization of nanoscaffolds was performed by Box-Behnken Design in which two independent formulation variables and one independent process variable: poly(lactic-co-glycolic acid) (PLGA) (X 1), Pluronics F-127 (X 2), and rotation speed (X 3) were used. The design provided 15 formulation designs which were prepared to determine the response: percentage porosity (Y 1) and drug loading (Y 2). Polynomial equations were generated and analyzed statistically to establish a relationship between independent and dependent variables and develop an optimal formulation with maximized porosity (%) and drug loading (%). The optimized formulation batch was prepared using 19.18% w/v PLGA, 4.98% w/v Pluronics at 500 rpm rotation speed and exhibited drug loading of 11.66% and porosity of 82.62%. Further, correlation between the independent and dependent variables were established and statistically analyzed by using model generated mathematical regression equations, ANOVA, residual plots, interaction plot, main effect plot, contour plot and response surface designs. The analysis of model showed the significant individual effect of PLGA and significant interactive effect of Pluronics F-127 and rotation speed on drug loading and porosity. Further, its physicochemical characterization, and in-vitro (drug release kinetics, and PAMPA study), ex-vivo (enzyme inhibition assay and pro-inflammatory cytokines study) and in-vivo (neurobehavioral and histological study) studies were performed to evaluate the potential of memantine-loaded nanoscaffolds in the treatment of Alzheimer’s disease (AD). © 2022 IOP Publishing Ltd.
Dual targeting pH responsive chitosan nanoparticles for enhanced active cellular internalization of gemcitabine in non-small cell lung cancer
(Elsevier B.V., 2023) Krishan Kumar; Shiv Govind Rawat; Manjit; Mohini Mishra; Priya; Ajay Kumar; Ruchi Chawla
Lung cancer (LC), related with the enhanced expression of epidermal growth factor receptor (EGFR) and sialic acid binding receptors (glycan) brought about the development of EGFR and glycan receptor specific anticancer therapeutics. The current study assessed the formulation, physiochemical characterization, in vitro and in vivo effects of sialic acid (SA) and cetuximab (Cxmab) decorated chitosan nanoparticles (CSN-NPs) loaded with gemcitabine (GMC) targeted to glycan and EGFR over-expressing non-small-cell lung-cancer (NSCLC) A-549 cells. Chitosan (CSN) was conjugated with sialic acid via EDC/NHS chemistry followed by gemcitabine loaded sialic acid conjugated chitosan nanoparticles (GMC-CSN-SA-NPs) were prepared by ionic gelation method decorated with Cxmab by electrostatic interaction. In vitro cytotoxicity of NPs quantified using cell based MTT, DAPI and Annexing-V/PI apoptosis assays showed superior antiproliferative activity of targeted nanoformulations (GMC-CSN-SA-Cxmab-NPs ≫ GMC-CSN-SA-NPs, GMC-CSN-Cxmab-NPs) over non-targeted nanoformulation (GMC-CSN-NPs) against A-549 cells. In vivo pharmacokinetic study showed superior bioavailability and in vivo therapeutic efficacy investigation exhibited strongest anticancer activity of glycan and EGFR targeted NPs (GMC-CSN-SA-Cxmab-NPs). GMC-CSN-SA-Cxmab-NPs demonstrated enhanced cellular internalization and better therapeutic potential, by specifically targeting glycan and EGFR on NSCLC A-549 cells and B[a]P induced lung cancer mice model, hence it might be a good substitute for non-targeted, conventional chemotherapy. © 2023 Elsevier B.V.
Factorial Design-Based Nanocarrier Mediated Formulation of Efavirenz and Its Characterization
(World Scientific, 2022) Ruchi Chawla; Venkatanaidu Karri; Varsha Rani; Mohini Mishra; Krishan Kumar
Efavirenz (EFV) suffers from poor aqueous solubility which results in low bioavailability of the drug. Nanocarrier-based drug delivery systems offer a suitable alternative for improving the physico-chemical properties of the drug and hence its efficacy. Nanosuspension (NS) of EFV was formulated by solvent-anti solvent precipitation method using PVP K-30 as stabilizer and sodium lauryl sulphate (SLS) as the wetting agent. Multi-level factorial design was applied to select the optimal formulation which was further characterized. The optimal batch exhibited mean particle size of 305nm and polydispersity index (PDI) of 0.345. Solid-state characterization studies of the NS conducted using scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction, and differential scanning calorimetry (DSC) revealed compatibility between the drug and the excipients and modest alteration in the crystallinity of the drug. There was progressive increase in the solubility of the drug when incorporated in NS from 17.39μg/ml to 256μg/ml. Further, drug release studies showed significantly better and controlled drug release pattern in comparison to the free drug due to the presence of nanosized particles in the formulation. © 2022 World Scientific Publishing Company.
Intranasal curcumin and its evaluation in murine model of asthma
(2013) Subhashini; Preeti S. Chauhan; Sharda Kumari; Jarajana Pradeep Kumar; Ruchi Chawla; D. Dash; Mandavi Singh; Rashmi Singh
Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3 h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect. © 2013 Elsevier B.V.
Intranasal micellar curcumin for the treatment of chronic asthma
(Editions de Sante, 2022) Ruchi Chawla; Bhupendra Sahu; Mohini Mishra; Varsha Rani; Rashmi Singh
Curcumin is a natural phytoconstituent obtained from the rhizomes of Curcuma longa (turmeric) and is known for its diverse anti-oxidant and anti-inflammatory benefits, but its clinical utility is limited by its poor aqueous solubility and rapid metabolism, which ultimately affects its bioavailability. The present study is focused on the formulation of curcumin loaded micellar dispersion for intranasal delivery for the treatment of chronic asthma. Micellar dispersion was prepared by film formation method using poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG5000-DSPE) as lipid surfactant and characterized for its physic-chemical properties. The curcumin micelles were evaluated for their anti-asthmatic action in ovalbumin (OVA)-induced allergic asthma model in male wistar rats against standard drug dexamethasone. The micelles showed mean particle size in the range of 20.03 nm–26.48 nm. The micellar dispersion exhibited negative zeta potential in the range of −26.22 to −25.52 mV. Incorporation of curcumin into micelles helped in enhancing the solubility of curcumin besides providing it protection against degradation. In vitro studies showed sustained relase of curcumin up to 36 h. A 14- fold increase in the bioaviability of the curcumin was measured when administered as micelles. In addition, 4.4- fold higher concentration of drug was measured in the lungs for micellar curcumin. Comparable reduction in the levels of intracellular ROS was observed for i.n. curcumin-micelles (approx.57.6%) and dexamethasone (59.3%). Also, micellar curcumin produced significant supression (p < 0.05) in the release of nitric oxide. Through the present study, we can suggest the potential application of curcumin micelles in the treatment of asthma. © 2021 Elsevier B.V.
Nanoparticulate Carriers-Versatile Delivery Systems
(wiley, 2021) Ruchi Chawla; Varsha Rani; Mohini Mishra
Recently, significant efforts have been made on the development of biocompatible and biodegradable nanoparticulate carrier systems like polymeric nanoparticles, solid lipid nanoparticles, liposomes, etc. for delivery of drugs because of their potential benefits such as enhanced drug permeability, cell adhesion, cytotoxicity and cell attachment, improved bioavailability, reduced systemic toxicity, reduced local irritation, predictable gastric emptying, and improved pharmacokinetic behavior in comparison to conventional (monolithic) formulations. The sub-cellular and sub-micron size of nanoparticles facilitates trafficking and sorting into deep tissues through capillaries or fenestrations and also into different intracellular compartments such as macrophages, dendritic cells, etc. The delivery to target site and tissues can be controlled by engineering the polymer/lipid characteristics for their molecular weight, size, aqueous solubility, etc. The nanoparticulate carriers can be targeted both actively and passively. Conjugation with receptor-specific ligands results in active targeting with potential delivery of drugs to the target tissue. Autophagy is an example of passive targeting mechanism in which circulating cytoplasmic cells or organelles engulf the drug carriers (like in tuberculosis). Besides use of nanocarriers for delivery of drugs, they can also be used for delivery of DNA in gene therapy and administer proteins, peptides, and genes via peroral route. Thus, the nanoparticulate drug carriers have versatile applications in drug delivery and treatment of diseases. © 2021 Scrivener Publishing LLC.
Negatively charged liposomes of sertraline hydrochloride: Formulation, characterization and pharmacokinetic studies
(Editions de Sante, 2020) Tejpratap Chauhan; Varsha Rani; Bhupendra Sahu; Adity Sharma; Subhash Chand Kheruka; Sanjay Gambhir; Veeresh Dube; Lalit M. Aggarwal; Ruchi Chawla
The present study was carried out with an objective to study the extent of delivery of negatively charged liposomes of sertraline hydrochloride to brain via intravenous route for treatment of depressive –like symptoms. Liposomes of sertraline hydrochloride were formulated by film hydration technique using cholesterol, hydrogenated soya phosphatidylcholine-L-α-phosphatidylcholine, and distearoyl phosphatidyl glycerol sodium. Uniform sized vesicles with porous surface morphology with vesicle size of 151.59 nm were prepared. Radioactive imaging performed using 99mTcO4 showed ~5% of uptake of labelled liposomes in brain within 2 h of administration. On administration of liposomes and free drug suspension, approximately, 205.06 ng/ml and 87.18 ng/ml of sertraline were estimated in brain at 36 h. The liposomes can be transported by transcelluar transport which includes phagocytosis and the use of phosphatidylcholine enhances macrophage internalization and delivery to brain. The study indicated significantly higher concentration of sertraline in brain after 36 h, on administration of liposomes as compared to free sertraline suspension. © 2020 Elsevier B.V.
Organ-targeted drug delivery systems (OTDDS) of poly[(N-acryloylglycine)-co-(N-acryloyl-l-phenylalanine methyl ester)] copolymer library and effective treatment of triple-negative breast cancer
(Royal Society of Chemistry, 2025) Sukanya Patra; None Jyotirmayee; Krishan Kumar; Divya Pareek; Prem Shankar Gupta; Anjali Ramsabad Mourya; Taniya Das; Kirti Wasnik; Malkhey Verma; Ruchi Chawla; Tarun K. Batra; Pradip Paik
Organ-targeted drug delivery systems (OTDDS) are essential for the effective treatment of complicated diseases. Triple-negative breast cancer (TNBC) is an aggressive cancer with high mortality and requires targeted therapeutics. This work was aimed at designing a library of polymeric OTDDS with N-acryloyl-glycine (NAG) and N-acryloyl-l-phenylalanine methyl ester (NAPA) [p(NAG-co-NAPA)(x:y)] and screening its in vivo organ-targeting specificity. Among this library, the best p(NAG-co-NAPA)(x:y) NPs with an x : y ratio of 1 : 4 and size of 160-210 nm targeted breasts to a high extent compared to other organs and thus were optimized for TNBC treatment. A network pharmacology study was performed, which revealed that 14 genes were responsible for TNBC, and a combination of DHA (targets 6 genes) and piperine (targets 8 genes) drugs was used to optimize the formulation, achieving the maximum therapeutic efficiency against TNBC with an IC50 value of 350 μg mL−1. The designed organ-specific polymeric nanoparticle (NP) library, identification of target genes and proteins responsible for TNBC, and the optimized formulation for effective combination therapy established an effective therapeutic option for TNBC. The findings of this work further demonstrate that this polymeric library of NPs shows exciting therapeutic potential for treating TNBC and presents innovative treatment options for critical diseases of the liver, heart, lungs and kidney. © 2025 The Royal Society of Chemistry.
Polylactide-co-glycolide nanoparticles of antitubercular drugs: Formulation, characterization and biodistribution studies
(Future Science Ltd, 2014) Ruchi Chawla; Harshendra S. Solanki; Subhash Chand Kheruka; Sanjay Gambhir; Veeresh Dube; Lalit M. Aggarwal; Brahmeshwar Mishra
Background: The present study was designed to prepare and characterize poly lactide-co-glycolide nanoparticles of antitubercular drugs (ATDs) for delivery through oral route to alveolar macrophages. Methods: Nanoparticles were prepared by double emulsification solvent evaporation method. Ex vivo and in vivo drug accumulation studies were performed in alveolar macrophages, harvested by broncheoalveolar lavaging. Internalization of nanoparticles was studied by confocal laser scanning microscopy. γ-scintigraphy imaging using technetium-99m was done to study the biodistribution pattern of nanoparticles. Results: High intracellular concentrations of ATDs were observed in macrophages within 30 min of administration of nanoparticles. Intense radioactivity recorded in liver, spleen and lungs revealed uptake of nanoparticles in macrophages, abundantly present in mononuclear phagocyte system present in these organs. Conclusion: Targeted delivery of ATDs will help reduce dose and associated side effects including hepatotoxicity of ATDs. Further studies are required to assess the potential therapeutic advantages for treatment of TB. © 2014 Future Science Ltd.