Hafsa Ahmad

Mimosa pudica L. (Laajvanti): An overview

Mimosa pudica L. (Mimosaceae) also referred to as touch me not, live and die, shame plant and humble plant is a prostrate or semi-erect subshrub of tropical America and Australia, also found in India heavily armed with recurved thorns and having sensitive soft grey green leaflets that fold and droop at night or when touched and cooled. These unique bending movements have earned it a status of ‘curiosity plant’. It appears to be a promising herbal candidate to undergo further exploration as evident from its pharmacological profile. It majorly possesses antibacterial, antivenom, antifertility, anticonvulsant, antidepressant, aphrodisiac, and various other pharmacological activities. The herb has been used traditionally for ages, in the treatment of urogenital disorders, piles, dysentery, sinus, and also applied on wounds. This work is an attempt to explore and compile the different pharmacognostic aspects of the action plant M. pudica reported till date.

Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats.

Abstract 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 optimization and development of a liposomal delivery system for efficient delivery of NMITLI118RT+ [a standardized ethanolic extract of a new chemotype of W. somnifera Dunal (NMITLI-118) roots] against cerebral stroke in rats. Liposomal systems were prepared using thin-film hydration method and characterized on the basis of size, zeta potential, physical stability, FT-IR, DSC-TGA analysis and surface morphological studies by TEM. NMITLI118RT+ and its formulations (NMITLI118RT+LF) were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. The Z average of the developed liposomal formulation was about 142.6 ± 0.09 nm with a zeta potential of −31.20 ± 1.0 mV. Results of TEM revealed spherical particles in the range of 200 nm. The entrapment efficiency was found to be 94.603 ± 2%. The formulation was found to be physically stable over a 3-week period. Results were suggestive of the fact that both NMITLI118RT+ and its delivery system possess significant neuroprotective activity in cerebral ischemia. The liposomal system largely exhibits better performance over NMITLI118RT+ precisely in the post-treatment group. The present studies could elucidate the successful development of a delivery system for NMITLI118RT+ and demonstrate their beneficial neuro-protective potential in overcoming and reversing the consequences of I/R injury following stroke.

PEGylated chitosan nanoparticles potentiate repurposing of ormeloxifene in breast cancer therapy.

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 polydispersity index and spherical shape with +31 mV surface charge. CNPs10 had 88.37% entrapment efficiency and 20.93% loading efficiency. CNPs10 demonstrated dose-dependent enhancement in cytotoxicity, cellular uptake, apoptosis, disruption of mitochondrial membrane potential and activation of caspase-3 in breast cancer MDA-MB-231 and MCF-7 cells over free ormeloxifene. In vivo studies divulged improved pharmacokinetic parameters, reduced toxicity, suppressed tumor burden and increased survival in CNPs10-treated female Sprague-Dawley rats. CONCLUSION PEGylated CNPs enhanced anticancer activity of ormeloxifene.

Phospholipid complexation of NMITLI118RT+: way to a prudent therapeutic approach for beneficial outcomes in ischemic stroke in rats

Abstract 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, NMITLI-128. In this study the investigators have attempted development of a phytosomal complex of NMITLI118RT + (standardized ethanolic extract of a new chemotype of W. somnifera Dunal.), its pharmaceutical characterization and evaluation of its neuro-protective potential against experimenal stroke in rats in continuation with their previous work in this area. The phytosomal complex (NIMPLC) was prepared by following a cohesive optimization design and was characterized on the basis of solubility, dissolution profile, FT-IR, DSC-TGA analysis, zeta potential, physical stability, forced degradation and photolytic degradation. Results were suggestive of a pharmaceutically acceptable formulation. NIMPLC was taken up further for biological evaluation using the middle cerebral artery occlusion (MCAO) model in rats. It could be demonstrated that the beneficial effects of NMITLI118RT + could be augmented by NIMPLC in 1 h pre and 6 h post treatment as was evident from reduction in MDA levels, increment in GSH levels, reduction in neurological deficit (ND) scores and reduction in infarct size. The study could successfully demonstrate the beneficial effects of NIMPLC in brain function restoration following stroke.

Anticancer Effects of Extracts from the Fruit of Morinda Citrifolia (Noni) in Breast Cancer Cell Lines.

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 synergistic effect of various natural ingredients gets lost. They generally constitute polyphenols and flavonoids. Studies have suggested that these phytochemicals, especially polyphenols, display high antioxidant properties, which help to reduce the risk of degenerative diseases, such as cancer and cardiovascular diseases. Several in-vitro and in-vivo studies have shown that Noni fruits have antioxidant, anti-inflammatory, anti-dementia, liver-protective, anticancer, analgesic, and immunomodulatory effects. Till date about 7 in vitro cancer studies have been done, but a detailed in vitro study including cell cycle and caspase activation assay on breast cancer cell line has not been done. In the present study different Noni fruit fractions have tested on cancer cell lines MCF-7, MDA-MB-231 (breast adenocarcinoma) and one non-cancer cell line HEK-293 (Human embryonic kidney). Out of which ethylacetate extract showed a higher order of in vitro anticancer activity profile. The ethylacetate extract strongly inhibited the proliferation of MCF-7, MDA-MB-231 and HEK-293 cell lines with IC50 values of 25, 35, 60 µg/ml respectively. The extract showed increase in apoptotic cells in MCF-7 and MDA-MB-231 cells and arrested the cell cycle in the G1/S phase in MCF-7 and G0/G1 phase in MDA-MB-231 cells. Noni extract also decreases the intracellular ROS generation and mitochondrial membrane potential.

Co-delivery of hesperetin enhanced bicalutamide induced apoptosis by exploiting mitochondrial membrane potential via polymeric nanoparticles in a PC-3 cell line

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 by ionic gelation method, and showed narrow particle size distribution, high encapsulation efficiency (about 90%) and sustained drug release behavior for both drugs. During the preparation of NPs; HSP crystallinity was retained, whereas polymorphic transition of BCT from form I to form II was observed by thermogravimetric analysis. Additionally, DPPH radical scavenging assay confirmed the structural integrity of HSP in the NPs. The kinetic solubility of BCT and HSP in the NPs was increased by 61.66 and 6.75 fold, respectively, as compared to the free drugs. Further, the in vitro therapeutic efficacy of co-loaded PCL-BCT-HSP-CS NPs was compared with free BCT, HSP and their combination (BCT plus HSP) in androgen independent PC-3 cell lines. Interestingly, co-loaded NPs exhibited higher in vitro cytotoxicity by G1-S phase cell cycle arrest and apoptosis at equivalent concentrations. This superior activity may be attributed to enhanced mitochondrial membrane potential loss by co-loaded NPs. Cell uptake study showed significantly higher (P < 0.05) uptake of NPs by cancer cells. Additionally, in vivo pharmacokinetics of NPs were explored in SD male rats and revealed higher AUC0–t and Cmax of BCT (1.46 and 1.42 fold) and HSP (4.16 and 3.79 fold) than an aqueous suspension when administered orally at 20 mg kg−1. We demonstrated that co-delivery with HSP via polymeric NPs might have better therapeutic potential for in vitro management of androgen independent prostate cancer.

Validation of RP-HPLC Method for Simultaneous Quantification of Bicalutamide and Hesperetin in Polycaprolactone-Bicalutamide-Hesperetin-Chitosan Nanoparticles

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 performance liquid chromatographic method for simultaneous estimation of bicalutamide and hesperetin. The validation parameters such as specificity, linearity, precision and accuracy, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization ICH Q2 (R1) guidelines. Chromatographic separation was achieved on Lichrocart(®) CN column (250 × 4 mm, 5 µm, MERCK) with isocratic elution. The retention times and detection wavelength, for hesperetin and bicalutamide were 4.28 min, 288 nm and 5.90 min, 270 nm respectively. The intra-day and inter-day assay precision and accuracy were found to be <2% over linearity of 50-2000 ng/mL with R(2) 0.999. LOD and LOQ, of bicalutamide and hesperetin was 14.70, 44.57 ng/mL and 16.11, 48.84 ng/mL, respectively. The method was successfully applied for encapsulation efficiency and drug release studies from bicalutamide and hesperetin loaded nanoparticles.

Stability indicating studies on NMITLI 118RT+ (standardized extract of withania somnifera dunal)

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. somniferas root extract, which has been used for the present study. Objectives: The present investigation aims to develop and validate a simple isocratic reverse phase-high performance liquid chromatography (RP-HPLC) system for the detection and estimation of Withanolide A (marker compound) and its analytical application for stability indicating studies on NMITLI-118RT+. Material and Methods: A validated RP-HPLC method for Withanolide A was established on a Waters HPLC system and the same was used on NMITLI-118RT+ for quantification and fingerprinting purposes, and for establishing forced degradation, isothermal stress tests, and drug-excipient testing protocols as per International Conference on Harmonization (ICH) guidelines. Results: A validated method was established, which could detect the marker at a retention time of around 6.3 minutes, with a linearity range of 2-100 μg/mL, by varying the amounts of the said marker, which were estimated in four different batches of NMITLI-118RT+. Photostability as per ICH guidelines suggested a slight loss of the active constituent and maximum degradation was afforded with alkali followed by acid, and then peroxide, in the forced degradation studies. In the drug-excipient studies, the maximum amount of active constituent could be detected in the samples with ethyl cellulose and the least with hydroxy propyl cellulose. Conclusion: The method developed here was simple and rapid. The various stability indicating studies carried out in the present investigation would be useful for formulation development and were suggestive of deciding the recommended storage conditions for NMITLI-118RT+.

Effect of polydimethylsiloxane and ethylcellulose on in vitro permeation of centchroman from its transdermal patches

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. The physicochemical compatibility of the drug and the polymers was performed by differential scanning calorimetry and Fourier transform infrared (FTIR) spectroscopic technique. Effects of EC and PDMS ratios on moisture uptake, moisture content, tensile strength (TS), Young’s modulus, adhesive strength, water vapor transmission rate (WVTR) and in vitro permeation of centchroman through Sprague–Dawley rats abdominal skin using Franz’s diffusion cell were evaluated. A 32 full factorial design was employed to observe the effect of independent variables; concentration of ethyl cellulose and PDMS on drug permeated after 32 h, which was selected as dependent variable. Compatibility studies suggested that there were no significant interaction between the drug and polymers used. It was found that incorporation of only EC resulted in too hard patches and addition of PDMS produced patches with lower TS, increased percentage elongation, WVTR and Young’s modulus. Statistical analyses suggested that independent variables have a significant effect on the dependent variable. All formulation follows zero-order release kinetics with r2 > 0.990. In conclusion, drug in adhesive transdermal patches can be successfully fabricated for non-steroidal contraceptive centchroman to obtain a zero-order release systems.

Synthesis and Evaluation of Chirally Defined Side Chain Variants of 7-Chloro-4-Aminoquinoline To Overcome Drug Resistance in Malaria Chemotherapy

ABSTRACT 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 parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.