Anil K Dwivedi

Central Drug Research Institute | CDRI · Pharmaceutics Division (CDRI)

The aim of the study was to develop oral arteether (AE) nano formulations, to investigate their effects in rats, and for the complete and effective treatment of Plasmodium yoelii nigeriensis infected mice at a reduced dose by increasing the relative bioavailability. Nano-formulations of arteether have been developed. The relative bioavailability (R...

Introduction: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models. Methods: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (ST...

Diabetes mellitus had emerged as a metabolic menace which leads to the development of dyslipidemia, myocardial infarction, coronary artery diseases, obesity and hypertension. These are critical hallmarks for severe metabolic disorders owing to lack of proper balance between the energy intake and energy consumed. Previously, various potent biomarker...

Ethno-pharmacological relevance Withania somnifera (L.) Dunal, commonly known as Ashwagandha, belongs to the family Solanaceae. In Ayurveda, Ashwagandha has been defined as one of the most important herb and is considered to be the best adaptogen. It is also an excellent rejuvenator, a general health tonic and cure for various disorders such as cer...

We investigated the preclinical efficacy and safety/tolerability of biodegradable polymeric particles containing isoniazid (INH) and rifabutin (RFB) dry powder for inhalation (DPI) as an adjunct to oral first-line therapy. Mice and guinea pigs infected with Mycobacterium tuberculosis H37Rv (Mtb) were treated with ∼80 and ∼300 μg of the DPI, respect...

Ethnopharmacological relevance Withanone (WN), an active constituent of Withania somnifera commonly called Ashwagandha has remarkable pharmacological responses along with neurological activities. However, for a better understanding of the pharmacokinetic and pharmacodynamic behavior of WN, a comprehensive in-vitro ADME (absorption, distribution, m...

Lipid solubility and molecular size are the major limiting factors for any molecule to get absorbed across biological membrane systems. Formulation strategies that address these concerns are of enormous benefit in eliciting the intended response from a therapy. Liposomes and phytosomes are two very versatile lipid-based delivery systems that cater...

Withania somnifera Dunal (Solanaceae), populaly known as Ashwagandha or Indian ginseng has been used in the traditional systems of medicine since several thousand years. CSIR-India has developed several chemotypes of this plant (NMITLI-101, NMITLI-118, NMITLI-128). The one currently being explored is NMITLI118R which is characterized by high root y...

Aims: Recently, strategies of cancer treatment using combination of agents with distinct molecular mechanism(s) of action are considered more promising due to its high efficacy and reduced systemic toxicity. The study is aimed to improve the efficacy of selective estrogen receptor modulator, Centchroman (CC) by combination with the phytoestrogen G...

The histamine 3 receptor (H3R) is a presynaptic receptor, which modulates several neurotransmitters including histamine and various essential physiological processes, such as feeding, arousal, cognition and pain. The H3R is considered as a drug target for the treatment of several central nervous system disorders. We have synthesized and identified...

Poly(lactide-co-glycolide) (PLGA) is a synthetic linear copolymer approved by the USFDA. It provides versatile biodegradable interventions such as 3D scaffolds for tissue engineering. PLGA systems are biocompatible and can be surface modified for intracellular interactions. Its biodegradation rate can be controlled and it is suitable for clinical a...

The hexane soluble extract of Curcuma longa (Turmeric) [herbal medicament (HM)] developed by Central Drug Research Institute, India, as a new antistroke agent. It contains carbonyl as well as non‐carbonyl compounds. To see the activity of non‐carbonyl compounds, HM was reacted with semicarbazide hydrochloride to remove the carbonyl compounds. This...

Ischemic stroke is a leading cause of mortality worldwide with limited treatment options. Since its pathophysiology involves free radical production, excitotoxicity, and stimulated inflammatory processes, therapeutic agents that can counter oxidative stress and associated inflammation could provide neuroprotection in the advent of cerebral stroke....

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A synthetic molecule S006-830, belonging to the class of thiophene-containing trisubstituted methanes, had shown good in vitro and in vivo bactericidal activity against drug-sensitive and drug-resistant Mycobacterium tuberculosis (Mtb). The molecule had also shown good druglike pharmacokinetic properties. However, S006-830 is a racemic mixture of t...

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer a...

Background: Turmeric (Curcuma longa) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. Objective: In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along wi...

Addressing multidrug resistant stage of breast cancer is an impediment for chemotherapy. Moreover, breast cancer chemotherapy has potential enduring confrontations i.e. related toxicity including effect on fertility of young female patients. The co-delivery of polyphenolic bio-enhancers with oleanolic acid in chitosan coated PLGA nanoparticles was...

The hybrid congener 3 derived from hydroxychalcone and pharmacophore oxypropanolamine for adrenergic receptor, along with its enantiomers 9a and 9b were selected from a series of compounds for detailed studies of their antidiabetic profile in sucrose-challenged, low-dosed, streptozotocin-induced diabetic rats and in db/db mice, and antidyslipidaemi...

A novel 4-aminoquinoline derivative ((S)-7-chloro-N-(4-methyl-1-(4-methylpiperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate) exhibiting curative activity against chloroquine resistant malaria parasite has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed SAR studies, has go...

In the present study, we designed Bicalutamide (BCT) and Hesperetin (HSP) co-loaded self nano-emulsifying drug delivery system (SNEDDS) to encounter the problem of BCT induced toxicity, low solubility, and bioavailability. Optimized BCT-HSP SNEDDS would produce an emulsion of globule size 30.84 ± 1.24 nm with a high encapsulation efficiency of BCT...

Rutin, a natural flavonol glycoside is known to possess significant radical scavenging properties which might have beneficial effects in cerebral ischemia. However its oral administration and pharmaceutical use is limited due to its poor aqueous solubility and bioavailability. The current investigation aimed at development of rutin–phospholipid com...

Objective: Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the o...

Withania somnifera Dunal (Solanaceae) known as Ashwagandha, a popular plant of Indian origin is known to possess tremedous medicinal potential, often used as anti-inflammatory, anti-platelet, antihypertensive, hypoglycemic, hypolipidemic and adaptogenic candidate. Some of its chemotypes developed by CSIR, India includes NMITLI-101, NMITLI-118, NMIT...

Today there is an urgent need for safe and effective dual-purpose contraceptive agents, which can simultaneously prevent unintended pregnancies and sexually transmitted infections (STI). There are several naturally occurring antimicrobial and antibiotic drugs (novobiocin, coumermycin and chlorobiocin) reported in the literature, which are based on...

Aim: Development and optimization of ormeloxifene-loaded PEGylated chitosan nanoparticles (CNPs) for enhancing its literature profound therapeutic activity against breast cancer. Methods: CNPs were prepared by ionotropic gelation method and characterized. Results: Optimized formulation (CNPs10) had average 304 nm particle size with 0.247 polyd...

The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L.) enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect an...

The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L.) enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect an...

Withania somnifera Dunal (Ashwagandha), is an Indian medicinal plant with significant pharmacological properties. Withanolides (steroidal lactones) are the chief constituents potentially responsible for its activity. Some of its chemotypes includes NMITLI-101, NMITLI-118, NMITLI-128. The present work elaborates the optimization and development of a...

The objective of this study is to develop a folic acid functionalized codelivery system for oral delivery of curcumin with bioenhancers (“trikatu”) to attenuate hormone refractory prostate cancer. Nanocur-bioenhancer exhibited significantly elevated cytotoxicity in prostate cancer cell line (PC3) compared to curcumin. Further, mechanistic studies i...

In this research, we reported the co-delivery of anti-androgen drug Bicalutamide (BCT) with Hesperetin (HSP) in chitosan (CS) coated polycaprolactone (PCL) nanoparticles (NPs) to increase their therapeutic efficacy against an androgen independent prostate cancer cell line. The PCL-BCT-HSP-CS NPs were prepared by anti-solvent precipitation followed...

Endothelial cell mediated inflammation flags and mediates the progression of pre and post myocardial infarction. The present study evaluated the effect of NCCL (a fraction of curcuma oil) in MI/RP injury. Using myocardial left coronary artery ligation and the reperfusion model, here, we show that NCCL-100 mg kg-1 possessed a better salutary effect...

In recent years the DNA minor groove has attracted much attention for the development of anti-malarial agents. In view of this we have attempted to discover novel DNA minor groove binders through in-silico and in-vitro workflow. A rigorously validated pharmacophore model comprising of two positive ionizable (PI), one hydrophobic (HY) and one ring a...

Ormeloxifene hydrochloride (Centchroman) is once-a-week non-steroidal oral contraceptive agent marketed in India and other countries. In this study, we report a validated isocratic high-performance liquid chromatographic (HPLC) method for chiral separation of d- and l-ormeloxifene hydrochloride. This method is capable of baseline separation of its...

Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergisti...

Bicalutamide is a non-steroidal anti-androgen drug used for the treatment of androgen-dependent prostate cancer. Hesperetin is a natural bioflavonoid that can be used in combination with bicalutamide to improve efficacy and decrease tolerance. The aim of the present work was to develop and validate a simple, sensitive, rapid reverse phase-high perf...

In the present study turmerone enriched curcuma oil (C.oil) obtained from Curcuma longa L. was evaluated in lipopolysaccharide (LPS) induced inflammation in THP-1 human monocytes, J774.2 murine macrophages and Swiss mice. THP-1, J774.2 and mice or human whole blood pre-treated with C.oil (1–30 µg/ml; 14 h) and stimulated with LPS (50 ng/ml–1 µg/ml)...

Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underl...

Withania somnifera Dunal is an Indian medicinal plant with significant pharmacological properties, such as adaptogenic, anti-inflammatory, anti-oxidant, anti-platelet, anti-hypertensive, hypoglycemic and hypolipidemic effects. Several chemotypes of W. somnifera include NMITLI-101, NMITLI-118 and NMITLI-128. The present work elaborates the optimizat...

S002-333, a novel anti-thrombotic agent, exhibits excellent platelet mediated antithrombotic action and subsequently has no effect on coagulation cascade. However, its oral bioavailability is hampered due to inherent low aqueous solubility. In order to circumvent this issue, chitosan coated liposomes were prepared by ethanol injection method. S002-...

Schizophrenia is a chronic disabling psychiatric disorder affecting 1% of the population worldwide. Due to the adverse effects of available antipsychotic medications, recent investigations have focused on the search for well-tolerated, safe molecules from natural resources to control the severity and progression of schizophrenia. To screen the stan...

Glucose uptake by Plasmodium-infected erythrocytes (RBC) is higher compared to uninfected RBC. Glucose is transported across the cell membrane by transporter proteins. Particles of median size 146.3±18.7nm, containing anti-malarial agents in corn starch were prepared for investigating: (a) whether the glucose moiety in starch targets RBC via hexose...

The aim of the study was to develop a drug delivery system for specific targeting in colon cancer. We have developed Eudragit S-100 (ES) coated folic acid (FA) conjugated gliadin (Gd) delivery system for the effective targeting to the over expressed folate receptors (FRs) in colon cancer. The FA conjugate with Gd (FA-Gd) was synthesized and charact...

The present work is focused on the preparation of nanoemulsions (NEs) loaded with arteether (ART) for its enhanced efficacy against malaria parasites. ART-NEs have been prepared using high pressure homogenization (HPH) technique with the aim of improving its solubility and thus its bioavailability. ART-NEs were optimized in terms of pressure and nu...

CDRI compound No. 97/78, a new trioxane derivative for the treatment of malaria, exhibits low aqueous solubility and high photosensitivity. The present study was undertaken to develop a sensitive and reproducible HPLC assay method for conducting stability studies and quality control of different batches as per International Conference on Harmonizat...

Based on the anti-mycobacterial activity of various acid hydrazides, a series of substituted 3-hydrazinyl-3-oxo-propanamides has been designed. The target compounds have been synthesized from diethylmalonate using substituted amines and hydrazine hydrate in ethanol. Computational studies and anti-tubercular activity screenings were undertaken to te...

In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced ar...

Context: Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored. Objective: The present study investigate...

A substituted 5-(piperidine-1-carbonyl) pyrrolidin-2-one (CDRI compound S007-867) is a potent antithrombotic candidate drug under development at our Institute. An HPLC method for determination of S007-867 with its intermediates has been developed and validated for in process quality control and stability studies. The analytical performance paramete...

Abstract The purpose of this study was to prepare and characterize the complexes between curcumin (CU) phosphatidylcholine (PC) and hydrogenated soya phosphatidylcholine (HSPC) and to evaluate their anticancer activity. These CU-PC and CU-HSPC complexes (CU-PC-C and CU-HSPC-C) were evaluated for various physical parameters like Fourier transform in...

Clarithromycin is a semi-synthetic macrolide anti-biotic exhibiting good antimicrobial activity over erythromycin and mefloquine is an anti-malarial agent against falciparum malaria. Clarithromycin, a cytochrome P450 inhibitor, can reportedly cause reversal of mefloquine resistance in Plasmodium strains. Hence a simple, sensitive, selective and rep...

Background: Withania somnifera Dunal (Ashwagandha) is an Indian medicinal plant of great medicinal value; used in many clinically proven conditions. NMITLI-118RT+ is a candidate drug under a Council of Scientific and Industrial Research (CSIR) networking project. It is a chemotype of W. somnifera's root extract, which has been used for the present...

Abstract A series of γ- butyrolactone derivatives has been designed and synthesized from commercially available 2-acetyl butyrolactone (3-acetyldihydrofuran-2(3H)-one, 1) by aminoalkylating its active methylene followed by condensation with different aldehydes. Compounds having amino group were further converted to their respective tartarate salts...

A series of γ- butyrolactone derivatives has been designed and synthesized from commercially available 2-acetyl butyrolactone (3-acetyldihydrofuran-2(3H)-one, 1) by aminoalkylating its active methylene followed by condensation with different aldehydes. Compounds having amino group were further converted to their respective tartarate salts and were...

Endothelial cells initiated inflammation persisting in post myocardial infarction needs to be controlled and moderated for avoiding fatal complications. Curcuma oil (C.oil, Herbal Medicament) a standardized hexane soluble fraction of Curcuma longa has possessed neuroprotective effect. However, its effect on MI/RP and endothelial cells remain incomp...

Curcuma longa (C. longa), a perennial herb, is a member of the Zingiberaceae (ginger) family and possesses a wide array of biological activity. Standardized hexane soluble extract of C. longa rhizomes [Herbal Medicament (HM)] had shown very good anti-stroke activity. A validated High Performance Liquid Chromatography (HPLC) analysis method for isoc...

Abstract This research aims at the development of controlled release contraceptive transdermal patches of centchroman using ethylcellulose (EC) as film-forming polymer, polydimethylsiloxane (PDMS) as pressure sensitive adhesive with propylene glycol and Di-n-butyl-phthalate for their penetration enhancer and plasticizing properties, respectively. T...

Context: Centchroman (Ormeloxifene) is a nonsteroidal SERM; popularly used as a contraceptive; hence controlled delivery systems become a favorable choice for its administration. Objective: The present work aimed at preparing depot injectable microspheres of centchroman by using ethyl cellulose and evaluating it on various parameters. Materials and...

In the present study, for the first time, HPLC method of CDRI compound S-001-469 is reported, S-001-469 is a new potential substituted chalcone based antidiabetic candidate drug under preclinical development phase. The current study illustrates comprehensive stress testing of S-001-469 under different prescribed ICH stress conditions. A reverse pha...

The present invention relates to novel substituted benzfurochromenes and related compounds having the general formula (I), salts and chiral, achiral derivatives thereof; wherein R1, R2, R3, R4, R5, R6, R7, R8 are independently selected from the groups consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally s...

Objective: The principle objective of this study was to develop 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS)-coated gelatin nanoparticles (GNPs) bearing amphotericin B (AmB) for specific targeting to the macrophages involved in visceral leishmaniasis (VL). Method: The two-step desolvation method has been used for the preparation of GNPs with Am...

Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergisti...

The present communication is focusing on development of safe nanotemplates for sustained delivery of amphotericin B (AmB). We synthesized a block copolymer based on chitosan and Pluronic F-127 (PEO–b–PPO–b–PEO). Selection of Pluronic F-127 was based upon the criteria’s that it has smaller size, higher aqueous solubility and stability whereas; chito...