Association of Dietary Factors and Physical Inactivity with Molecular Subtypes of Breast Cancer- Hospital Based Case-Control Study.

Improper diet and physical inactivity are environmental risk factors for breast cancer (BC). This study evaluated the association of dietary risk factors and physical activities with different molecular subtypes of BC. We conducted a case-control study among 130 cases of BC and 150 age-matched controls. Demographic data and tissue marker status were obtained. Diet was assessed using Food Frequency Questionnaire and physical activity was determined using Physical Activity Questionnaire. The association between diet and physical activity with the cancer status was evaluated by Pearson's Correlation. Among the various dietary factors, refined oil displayed a weak albeit significant positive correlation (r = 0.344) to Luminal B subtype of BC. Consumption of all kinds of non-vegetarian food exhibited significant elevation in BC risk with OR > 1.9 (95% CI 0.825-2.707). A higher odds ratio (>1.66) was observed in individuals who had a limited intake of fruits. Furthermore, a strong association was found between low physical activity and breast cancer risk, with around 14.6% of cases being distinctly linked to this risk (OR = 3.33, 95% CI 1.158-9.403, p < 0.01). In essence, while dietary factors exhibited a negative correlation with breast cancer risk, the risk was heightened by physical inactivity.

Self-nanoemulsifying drug delivery system of aqueous leaf extracts of Justicia adhatoda and Psidium guajava to enhance platelet count.

Self-nanoemulsifying drug delivery system (SNEDDS) containing aqueous leaf extracts of Justicia adhatoda (JA) and Psidium guajava (PG), was designed to evaluate their ability to enhance platelet count. The ternary phase diagram was constructed to identify the self-emulsifying regions and nanoemulsion prepared using clove oil, tween 80 and transcutol. The globule size of the prepared SNEDDS formulation at different folds of dilution in buffers of various pH was evaluated. The average globule size of the optimized JA2- and PG2-loaded SNEDDS at different folds of dilutions was in the range of 103.4 ± 7.1 to 238.3 ± 5.4 nm and 240.2 ± 7.9 to161.7 ± 3.7 nm, respectively. The viscosity of JA2 and PG2 loaded SNEDDS formulations were found to be 621 and 642 centipoise, respectively with no observed signs of phase separation, turbidity or precipitation during the freeze-thaw process. Oral administration of combined JA2 and PG2 loaded SNEDDS formulation to Wistar rats depleted with platelets showed a significant increase in platelet count when compared to a marketed tablet Caripill. Pharmacodynamic studies in platelet-depleted Wistar rats enhanced the platelet count after administration of SNEDDS containing lyophilized aqueous extracts JA2 and PG2.

Association of reproductive risk factors and comorbidities among molecular subtypes of Breast cancer in a Tertiary care Hospital

The reasons for the recently observed increase in the incidence of breast cancer in the Indian population are not clearly understood, but thought to be largely explained by westernization of lifestyles and changes in reproductive behavior, which characterize exposure to hormones. Our aim is to review the reproductive risk factors and comorbidities and evaluate the association between molecular subtypes of breast cancer. A hospital-based analytical case-control study was conducted among the breast cancer cases with controls in a multispecialty teaching hospital for a period of one year. Totally, 130 subjects were recruited and an interview was conducted using a structured questionnaire to obtain demographic and risk factor data, including tissue marker status (ER, PR and HER-2) obtained from case files. Data were analyzed with SPSS-20 version. Results: The highest age group reported in this study was 51- 60 years which has a 3.8 times increased risk compared to other age and the age group of 31- 40 have a decrease risk of 0.33. In this study, the percentage of post menopause (68%) and mothers not breastfeeding (10%) was higher in cases compared to controls and a noted increase in the risk of breast cancer with odds ratio (OR) of 2.745 (p= <0.0001) and 9.08 (p=0.01) respectively. Duration of breastfeeding showed significantly (p=<0.0001)) moderate positive correlation (r=0.549, 0.457, 0.418 and 0.636) for luminal A, luminal B, HER+, and triple negative respectively. This study found that all the reproductive risk factors do not have correlation with a molecular subtype of breast cancer except breastfeeding. Post menopause and breastfeeding were common factors associated with all people and could be modifiable to prevent the occurrence of breast cancer through lifestyle change

Building and behavior of a pH-stimuli responsive chitosan nanoparticles loaded with folic acid conjugated gemcitabine silver colloids in MDA-MB-453 metastatic breast cancer cell line and pharmacokinetics in rats.

The pH-stimuli release behavior of nanoformulations may enhance the success rate of chemotherapeutic drugs in cancers by site-specific delivery of drugs to cancer tissues. The aim of the present study was to prepare chitosan (CS) nanoparticles (NPs) with previously synthesized folic acid (FA) capped silver nanoparticles (AgNPs) loaded with the anti-cancer drug gemcitabine (GEM) (FA-GEM-AgNPs). The CS-FA-GEM-AgNPs (CS-NPs) were characterized with dynamic light scattering (DLS), transmission electron microscopy (TEM), energy dispersive x-ray analysis (EDAX), selected area electron diffraction (SAED), and differential scanning calorimetric (DSC) analyses. The in-vitro drug release of GEM was evaluated in media of different pH. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cytotoxic effects of the prepared nanoformulations in media with various pH. The time- and pH-dependent apoptotic cell death induced by CS-NPs with MDA-MB-453 human breast cancer cell line was observed using acridine orange (AO)/ethidium bromide (EtBr) staining. The pharmacokinetic parameters were studied with high-performance liquid chromatography (HPLC) and atomic absorption spectroscopy (AAS). Two batches of CS-NPs formulations were prepared, one with AgNPs of particle size 143 nm and the other with 244 nm. The particle size for CS-NPs-I (FA-GEM-AgNPs-143 nm) and CS-NPs-II (FA-GEM-AgNPs-244 nm) was found to be 425 and 545 nm, respectively. The zeta potential was found to be 36.1 and 37.5 mV for CS-NPs-I and CS-NPs-II, respectively. CS-NPs-I and CS-NPs-II showed a polydispersity index (PDI) of 0.240 and 0.261, respectively. A TEM study confirmed the spherical nature of the NPs. The nanoformulations exerted pH-dependant effect against MDA-MB-453 cells with relatively higher cytotoxicity at the lower pH than at higher pH levels. The pharmacokinetic profile and tissue distribution of CS-NPs in rats exerted drug release in a pH-dependent manner with enhanced excretion of Ag+. An optimized nanoformulation for pH-stimuli responsive release of GEM was successfully developed for future therapeutic exploration.

Exploring combined herbal extract-loaded phytoniosomes for antimalarial and antibacterial activity against methicillin-resistant Staphylococcus aureus.

Antibiotic resistance in the context of treating malarial infections is a major challenge in India. Home remedies such as thulasi leaves (Ocimum tenuiflorum), black pepper seeds (Piper nigrum), clove buds (Syzygium aromaticum), cinnamon bark (Cinnamomum verum), and nilavembu whole plant powder (Andrographis paniculata) were taken to explore antimalarial and methicillin-resistant Staphylococcus aureus (MRSA) activity. Among the five extracts, the best two extracts, C. verum and P. nigrum extract, showed the presence of Quercetin. Phytoniosomes were prepared by simple probe sonication with the two extracts and the resultant vesicles were in the size range of (319.7 nm). They showed significant (P < 0.001) antimalarial potency IC50 at 5.25 µg/ml against P. falciparum 3D7. In addition, their cytotoxicity (TC50) against Vero cell line was found to be > 100 µg/ml. The therapeutic index was found to be > 32 µg/ml. Phytoniosomes were converted to a capsule dosage form by lyophilization and this capsule was stable up to 90 days.

Synthesis and Characterization of Folic Acid Conjugated Gemcitabine Tethered Silver Nanoparticles (FA-GEM-AgNPs) for Targeted Delivery.

BACKGROUND: Silver nanoparticles (AgNPs) have attracted considerable interest in the medical industry due to their physicochemical properties, small size, and surface plasmon behavior. Their smaller particle size and instability in blood circulation leads to toxicity due to its aggregation as Ag+ ions and accumulation at the deepseated organ. In the present study, we aimed at reducing the toxicity of AgNPs by conjugation with an anticancer drug GEM and to improve their internalization through folate receptors-mediated endocytosis by capping the nanoparticles with folic acid (FA). METHODS: One-pot facile synthesis of FA capped silver nanoparticles (FA-AgNPs) has been achieved by using FA as a reducing agent. FA-AgNPs were mixed with Gemcitabine (GEM) to obtain tethered FA-GEM-AgNPs. Nanoparticles were characterized by Dynamic Light Scattering (DLS), UV-Visible spectroscopy, Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX), Selected Area Electron Diffraction (SAED), and Atomic Absorption Spectroscopy (AAS). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cytotoxic effect of the prepared nanoformulations. The apoptotic cell death induced by FA-GEM-AgNPs in breast cancer cells were monitored with Acridine orange (AO)/Ethidium Bromide (EtBr) staining. CONCLUSION: Compared to GEM and AgNPs, FA-GEM-AgNPs showed enhanced cytotoxic effect and internalization in MDA-MB-453 breast cancer cell line. FA-GEM-AgNPs could be an ideal candidate for targeting cancer cells via folate receptor-mediated endocytosis.

Molecular mechanism of tuberoinfundibular peptide of 39 on glucocorticoid receptor mediated glutamate/GABA imbalance and cerebral abnormalities against cognitive deficit model.

OBJECTIVES: This study is designed to evaluate the role of tuberoinfundibular peptide of 39 (TIP39) in connection with glucocorticoid receptor-mediated glutamate/GABA abnormalities in chronic unpredictable mild stress (CUMS) model. METHODS: Male Sprague-Dawley rats were treated with TIP39 (1 and 10 nmol, i.c.v) and diazepam 2 mg/kg throughout the stress period (28 days) in alternate days. Then, rats were subjected for different behavioural activity followed by biochemical, gene expression and histological examinations. KEY FINDINGS: Chronic unpredictable mild stress rats showed significant cognitive impairment in Morris water maze, Novel object recognition and Y maze test. This was reversed after TIP39 administration. Moreover, TIP39 significantly decreased the brain glutamate and acetyl cholinesterase levels in CUMS rats, whereas it increases the level of GABA after TIP39 treatment. These changes were evident with increased glutamic acid decarboxylase enzyme activity by TIP39. TIP39 significantly decreased the brain glucocorticoid and mineralocorticoid receptor expression ratio in comparison with CUMS rats. Moreover, histological abnormalities in prefrontal cortex and hippocampus were markedly improved after TIP39 administration in CUMS rats. CONCLUSIONS: Tuberoinfundibular peptide of 39 can be a potent neuroendocrine modulator in treating cognitive impairment induced by CUMS rats by controlling glucocorticoid receptor-mediated glutamate/GABA abnormalities in brain.

Development and evaluation of finasteride loaded ethosomes for targeting to the pilosebaceous unit.

Androgenetic alopecia, a major cause for baldness, is caused by the deposition of dihydrotestosterone (DHT) at the androgen receptors present in the pilosebaceous unit (PSU). Finasteride (FIN) is a potent 5α-reductase inhibitor capable of preventing the conversion of testosterone to DHT. But, its oral administration in males causes infertility. An attempt was made to prepare ethosomes of FIN with a size range 100-300 nm to enhance its delivery to the PSU. Finasteride loaded ethosomes (FES) were prepared using an ultra-probe sonicator and characterized for its size, morphology, surface charge and entrapment efficiency. The ability of FES to permeate across rat skin and frontal scalp skin of human cadaver was also evaluated. The spherical shaped ethosomes of different batches were in the size range of 107.8 ± 2.50 to 220.4 ± 6.92 nm and showed good permeation across rat skin and frontal scalp skin of human cadaver when compared to the unencapsulated FIN. The results portrayed the ability of FES to permeate across the stratum corneum to reach the PSU of the hair follicle. Although additional use of permeation enhancer increases the permeation of FIN across the skin, its addition may not be a favourable option for the deposition of ethosomes in the PSU.

Serious Drug-Drug Interactions in the Prescriptions of Diabetic Patients.

A large number of drugs are introduced every year, and newer interactions between medications are increasingly reported. Clinically significant drug interactions can occur when two or more drugs are taken in combination. With the continuing increase in the list of drugs capable of interactions, detection of these interactions from prescriptions becomes more important to ensure effective patient care. The aim of this study is to identify the possible drug interactions in the prescriptions of diabetic inpatients and to make physicians aware of these interactions to prevent the occurrence of clinically adverse effects. In a specially designed and validated data entry format, data for the following criteria were collected: drugs prescribed, major drug class prescribed, pharmacological classification of the observed drug interaction, and frequently occurring drug interactions. All the possible drug interactions were identified and evaluated using standard drug interaction reference books and databases. During the study period, 50 prescriptions of diabetic inpatients were screened randomly. Out of these prescriptions, 35 (70%) prescriptions had at least one possible drug-drug interaction. The major classes of drugs causing interactions included cardiac drugs (92%), analgesic drugs (66%), antibiotic drugs (52%), antidiabetic drugs (26%), diuretic drugs (26%), and antipsychotic drugs (24%). This study showed that 34 (68%) of the above prescriptions had minor interactions, 33(66%) had moderate interactions, and 10 (20%) had severe interactions. Of these, the drugs prescribed specifically for diabetes caused only nine moderate interactions. Thus, screening of prescriptions by the clinical pharmacist will help to minimize clinical occurrence of major/severe drug interactions in diabetic patients.

Preparation, characterization and in vitro cytotoxicity assay of curcumin loaded solid lipid nanoparticle in IMR32 neuroblastoma cell line.

Curcumin (diferuloylmethane) possesses low bioavailability due to its poor solubility, permeability and rapid metabolism. Solid Lipid Nanoparticle of curcumin was prepared by high-speed homogenization technique. Stearic acid was used as a lipid, tween 80 as surfactant and various co surfactants were used for the preparation of SLN. The prepared SLN was characterized using zeta sizer, TEM analysis and the average particle size was found to be in the range of 80 nm - 200nm. The entrapment efficiency of the SLN was ~58 to 85%. The characteristic FTIR peaks suggest that the stearic acid is compatible with curcumin. MTT assay was performed on the optimized formulation and the results are indicative that curcumin SLN showed better cytotoxicity in low dose while compared to plain curcumin. The developed Cu-SLN can find its better place in the anticancer therapy.

Formulation and optimization of Zidovudine niosomes.

Zidovudine (AZT) is commonly used to treat patients with AIDS, but it is limited by toxicity and high dosing needs. Alternative formulations have been proposed to overcome these drawbacks. The objective of this study was to evaluate process-related variables like hydration and sonication time, rotation speed of evaporation flask, and the effects of charge-inducing agent and centrifugation on zidovudine entrapment and release from niosomes. Formulation of zidovudine niosomes was optimized by altering the proportions of Tween, Span and cholesterol. The effect of process-related variables like hydration time, sonication time, charge-inducing agent, centrifugation and rotational speed of evaporation flask on zidovudine entrapment and release from niosomes was evaluated. The effect of changes in osmotic shock and viscosity were also evaluated. Non-sonicated niosomes were in the size range of 2-3.5 µm and sonicated niosomes formulated with Tween 80 and dicetylphosphate (DCP) had a mean diameter of 801 nm. Zidovudine niosomes formulated with Tween 80 entrapped high amounts of drug and the addition of DCP enhanced drug release for a longer time (88.72% over 12 h). The mechanism of release from Tween 80 formulation was the Fickian type and obeyed first-order release kinetics. Niosomes can be formulated by proper adjustment of process parameters to enhance zidovudine entrapment and sustainability of release. These improvements in zidovudine formulation may be useful in developing a more effective AIDS therapy.

Tissue distribution, pharmacokinetics and stability studies of zidovudine delivered by niosomes and proniosomes.

Niosomes containing zidovudine (ZDV), an anti-HIV drug for intravenous administration were formulated by a thin-film hydration technique. Proniosomes were prepared in the form of a slurry using beta-cyclodextrin as carrier. The effect of the surfactants Tween and Span and the negative charge-inducing agent dicetylphosphate (DCP) on tissue distribution of niosomes and proniosomes was studied. The distribution of ZDV in lungs, kidney, heart, liver and spleen of mice after intravenous bolus injection was higher in Tween 80 niosomes without DCP than either niosomes with DCP or Tween 80 proniosomes. The amount of ZDV in plasma was low in Tween 80 niosomes without DCP. The results of a pharmacokinetic study in rabbits confirmed that Tween 80 formulations with DCP were cleared from the circulation within five hours. An increased half-life of 202 minutes and mean residence time of 212.1 minutes was observed in Tween 80 formulation. A stability study showed that after 90 days of storage, the drug leakage from Tween 80 formulations stored at room temperature was significant (p < 0.001) compared to niosomes stored at 4 degrees C. Encapsulation ZDV in proniosomes reduced drug leakage from vesicles stored at room temperature. These results demonstrate that niosomes are a promising vehicle for targeted delivery of ZDV to macrophages in spleen and liver.