Directional molecular transport in iron redox flow batteries by interfacial electrostatic forces.

The mounting global energy demand urges surplus electricity generation. Due to dwindling fossil resources and environmental concerns, shifting from carbon-based fuels to renewables is vital. Though renewables are affordable, their intermittent nature poses supply challenges. In these contexts, aqueous flow batteries (AFBs), are a viable energy storage solution. This study tackles AFBs' energy density and efficiency challenges. Conventional strategies focus on altering molecule's solubility but overlook interface's transport kinetics. We show that triggering electrostatic forces at the interface can significantly enhance the mass transport kinetics of redox active molecules by introducing a powerful electrostatic flux over the diffusional flux, thereby exerting a precise directionality on the molecular transport. This approach of controlling the directionality of molecular flux in an all iron redox flow battery amplifies the current and power rating with approximately 140 % enhancement in the energy density.

Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma.

Fisetin (Fis), a natural flavonoid with anticancer effects, suffers from delivery constraints. Fisetin-nanostructured lipid carriers (NLCs) were developed for better efficacy against metastatic melanoma, employing the design of experiment (DoE) approach. The optimized NLCs depict a particle diameter of 135.0 ± 5.5 nm, a polydispersity index (PDI) of 0.176 ± 0.035, and an entrapment efficiency of 78.16 ± 1.58%. The formulation was stable over a period of 60 days and demonstrated sustained release of the drug (74.79 ± 3.75%) over 96 h. Fis-NLCs depicted at least ∼3.2 times lower IC50 value and ∼1.8 times higher drug uptake at 48 h in A-375 and B16F10 cells compared to that of Fis. It also inhibited the mobility of melanoma cells and induced cell cycle arrest at the G1/S phase. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot results show enhanced expression of Nrf2/NQO1 genes and an apoptotic effect by the upregulation of BAX mRNA expression. The protein levels of BAX and p53 were ∼2-fold higher compared with that of pure Fis. In-vivo studies demonstrated 5.9- and 10.7-fold higher inhibition in melanoma-associated metastasis in the lungs and liver, respectively. The outcomes from this study demonstrated Fis-NLCs as an effective tool against melanoma.

The multifaceted role of extracellular vesicles in prostate cancer-a review.

Prostate cancer is the second most prominent form of cancer in men and confers the highest mortality after lung cancer. The term "extracellular vesicles" refers to minute endosomal-derived membrane microvesicles and it was demonstrated that extracellular vesicles affect the environment in which tumors originate. Extracellular vesicles' involvement is also established in the development of drug resistance, angiogenesis, stemness, and radioresistance in various cancers including prostate cancer. Extracellular vesicles influence the general environment, processes, and growth of prostate cancer and can be a potential area that offers a significant lead in prostate cancer therapy. In this review, we have elaborated on the multifaceted role of extracellular vesicles in various processes involved in the development of prostate cancer, and their multitude of applications in the diagnosis and treatment of prostate cancer through the encapsulation of various bioactives.

A Concise Review on Natural Products and Their Derivatives for Breast Cancer Treatment.

Cancer is a leading cause of death worldwide. Among other cancers, breast cancer has been found to produce maximum number of cases in 2020. Different factors including geographical, genetic, hormonal, oral contraceptives and modern lifestyle could be responsible for the development of breast cancer and different pathways can be targeted for breast cancer treatment. The various conventional approaches used for the treatment of breast cancer including radiotherapy, chemotherapy, hormone and immunotherapy. But due to the side effects associated with these conventional treatments such as non-selectivity, multidrug resistance and bioavailability, there is a need for the development of better therapeutic agents for breast cancer treatment. Several natural products have been explored for breast cancer treatment. However, many of these natural products suffered from the limitations of poor water solubility and possess toxic side effects. To overcome these limitations, several structural analogs of natural products have been synthesized and possess potent anti-breast cancer effects with less side effects over their precursor molecules. In the present manuscript, we describe the pathogenesis of breast cancer, some potent natural products used in the treatment of breast cancer and their selected structural analogs possessing potent anti-breast cancer effects. Database such as Science direct, Pubmed and Google scholar were searched using keywords 'risk factors', 'screening methods','receptors', and 'natural products and derivatives', Registered clinical trials on selected natural products were also analyzed. Present study concludes that eight selected natural products and their derivatives possess wide potential to exhibit anti-breast cancer effects and could be explored further to develop better chemotherapeutic agents against breast cancer.

F3 peptide functionalized liquid crystalline nanoparticles for delivering Salinomycin against breast cancer.

Salinomycin (Sal) is a potent veterinary antibiotic known to offer significant toxicity to the variety of neoplastic cells. Its therapeutic utility is limited due to its higher lipophilicity (logP 7.5) and poor hydrophilicity. Liquid crystalline nanoparticles (LCNPs) known to offer a suitable delivery platform for these kinds of drugs. The overexpressed nucleolin receptor on the cell surface and cytoplasm, could be selected as a target in cancer therapy. The present study involves the development and characterization of the F3 peptide functionalized LCNPs for delivering Sal (F3-Sal-NPs) for selectively targeting to the nucleolin receptor. The optimized LCNPs were characterized for particle size, zeta potential, surface morphology, drug release kinetics and stability. The LCNPs have a structure similar to nematic phases. In vitro drug release studies revealed sustained drug release characteristics (89.5 ± 1.5% at 120 h) with F3-Sal-NPs. The cytotoxicity results demonstrated that F3-Sal-NPs were 4.8, 2.6 and 5.5 folds more effective than naïve drug in MDA-MB-468, MDA-MB-231 and MCF-7 cells, respectively and the cell cycle was arrested in the S and G2/M phases. The expression of the gene responsible for the stemness (CD44 gene), apoptosis (BAX/Bcl-2 ration) and angiogenesis (LCN-2) was reduced by F3-Sal-NPs treatment. Ex vivo hemolytic toxicity was reduced (6.5 ± 1.5%) and the pharmacokinetics and bioavailability of Sal was improved with F3-Sal-NPs. The in vivo antitumor efficacy was tested in EAC bearing mice, where F3-Sal-NPs significantly reduced the tumor growth by 2.8-fold compared to pure Sal and induced necrosis of tumor cells. The results clearly demonstrate the outstanding performance of F3 peptide functionalized LCNPs for delivering Sal against breast cancer.

Angiopep-2 Grafted PAMAM Dendrimers for the Targeted Delivery of Temozolomide: In Vitro and In Vivo Effects of PEGylation in the Management of Glioblastoma Multiforme.

The present study was aimed to synthesize, characterize, and evaluate the angiopep-2 grafted PAMAM dendrimers (Den, G 3.0 NH2) with and without PEGylation for the targeted and better delivery approach of temozolomide (TMZ) for the management of glioblastoma multiforme (GBM). Den-ANG and Den-PEG2-ANG conjugates were synthesized and characterized by 1H NMR spectroscopy. The PEGylated (TMZ@Den-PEG2-ANG) and non-PEGylated (TMZ@Den-ANG) drug loaded formulations were prepared and characterized for particle size, zeta potential, entrapment efficiency, and drug loading. An in vitro release study at physiological (pH 7.4) and acidic pH (pH 5.0) was performed. Preliminary toxicity studies were performed through hemolytic assay in human RBCs. MTT assay, cell uptake, and cell cycle analysis were performed to evaluate the in vitro efficacy against GBM cell lines (U87MG). Finally, the formulations were evaluated in vivo in a Sprague-Dawley rat model for pharmacokinetics and organ distribution analysis. The 1H NMR spectra confirmed the conjugation of angiopep-2 to both PAMAM and PEGylated PAMAM dendrimers, as the characteristic chemical shifts were observed in the range of 2.1 to 3.9 ppm. AFM results revealed that the surface of Den-ANG and Den-PEG2-ANG conjugates were rough. The particle size and zeta potential of TMZ@Den-ANG were observed to be 229.0 ± 17.8 nm and 9.06 ± 0.4 mV, respectively, whereas the same for TMZ@Den-PEG2-ANG were found to be 249.6 ± 12.9 nm and 10.9 ± 0.6 mV, respectively. The entrapment efficiency of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were calculated to be 63.27 ± 5.1% and 71.48 ± 4.3%, respectively. Moreover, TMZ@Den-PEG2-ANG showed a better drug release profile with a controlled and sustained pattern at PBS pH 5.0 than at pH 7.4. The ex vivo hemolytic study revealed that TMZ@Den-PEG2-ANG was biocompatible in nature as it showed 2.78 ± 0.1% hemolysis compared to 4.12 ± 0.2% hemolysis displayed by TMZ@Den-ANG. The outcomes of the MTT assay inferred that TMZ@Den-PEG2-ANG possessed maximum cytotoxic effects against U87MG cells with IC50 values of 106.62 ± 11.43 µM (24 h) and 85.90 ± 9.12 µM (48 h). In the case of TMZ@Den-PEG2-ANG, the IC50 values were reduced by 2.23-fold (24 h) and 1.36-fold (48 h) in comparison to pure TMZ. The cytotoxicity findings were further confirmed by significantly higher cellular uptake of TMZ@Den-PEG2-ANG. Cell cycle analysis of the formulations suggested that the PEGylated formulation halts the cell cycle at G2/M phase with S-phase inhibition. In the in vivo studies, the half-life (t1/2) values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were enhanced by 2.22 and 2.76 times, respectively, than the pure TMZ. After 4 h of administration, the brain uptake values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were found to be 2.55 and 3.35 times, respectively, higher than that of pure TMZ. The outcomes of various in vitro and ex vivo experiments promoted the use of PEGylated nanocarriers for the management of GBM. Angiopep-2 grafted PEGylated PAMAM dendrimers can be potential and promising drug carriers for the targeted delivery of antiglioma drugs directly to the brain.

Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics.

Cancer is one of the major causes of mortality, globally. Cancerous cells invade normal cells and metastasize to distant sites with the help of the lymphatic system. There are several mechanisms involved in the development and progression of cancer. Several treatment strategies including the use of phytoconstituents have evolved and been practiced for better therapeutic outcomes against cancer. Fisetin is one such naturally derived flavone that offers numerous pharmacological benefits, i.e., antioxidant, anti-inflammatory, antiangiogenic, and anticancer properties. It inhibits the rapid growth, invasiveness, and metastasis of tumors by hindering the multiplication of cancer cells, and prompts apoptosis by avoiding cell division related to actuation of caspase-9 and caspase-8. However, its poor bioavailability associated with its extreme hydrophobicity hampers its clinical utility. The issues related to fisetin delivery can be addressed by adapting to the developmental aspects of nanomedicines, such as formulating it into lipid or polymer-based systems, including nanocochleates and liposomes. This review aims to provide in-depth information regarding fisetin as a potential candidate for anticancer therapy, its properties and various formulation strategies.

Nanoconstructs for theranostic application in cancer: Challenges and strategies to enhance the delivery.

Nanoconstructs are made up of nanoparticles and ligands, which can deliver the loaded cargo at the desired site of action. Various nanoparticulate platforms have been utilized for the preparation of nanoconstructs, which may serve both diagnostic as well as therapeutic purposes. Nanoconstructs are mostly used to overcome the limitations of cancer therapies, such as toxicity, nonspecific distribution of the drug, and uncontrolled release rate. The strategies employed during the design of nanoconstructs help improve the efficiency and specificity of loaded theranostic agents and make them a successful approach for cancer therapy. Nanoconstructs are designed with a sole purpose of targeting the requisite site, overcoming the barriers which hinders its right placement for desired benefit. Therefore, instead of classifying modes for delivery of nanoconstructs as actively or passively targeted systems, they are suitably classified as autonomous and nonautonomous types. At large, nanoconstructs offer numerous benefits, however they suffer from multiple challenges, too. Hence, to overcome such challenges computational modelling methods and artificial intelligence/machine learning processes are being explored. The current review provides an overview on attributes and applications offered by nanoconstructs as theranostic agent in cancer.

A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of breast cancer with associated chemoresistance. The development of chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression of membrane proteins (transporters), epigenetic changes, and alteration of the cell signaling pathways/genes associated with the development of cancer stem cells (CSCs). AIM OF REVIEW: Due to the diverse and heterogeneous nature of TNBC, therapeutic response to the existing modalities offers limited scope and thus results in reccurance after therapy. To establish landmark therapeutic efficacy, a number of novel therapeutic modalities have been proposed. In addition, reversal of the resistance that developed during treatment may be altered by employing appropriate therapeutic modalities. This review aims to discuss the plethora of investigations carried out, which will help readers understand and make an appropriate choice of therapy directed toward complete elimination of TNBC. KEY SCIENTIFIC CONCEPTS OF REVIEW: This manuscript addresses the major contributory factors from the tumor microenvironment that are responsible for the development of chemoresistance and poor prognosis. The associated cellular events and molecular mechanism-based therapeutic interventions have been explained in detail. Inhibition of ABC transporters, cell signaling pathways associated with CSCs, and epigenetic modification offers promising results in this regard. TNBC progression, invasion, metastasis and recurrence can also be inhibited by blocking multiple cell signaling pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics and generating reactive oxygen species (ROS).

Dual role of Nrf2 in cancer: molecular mechanisms, cellular functions and therapeutic interventions.

BACKGROUND: Nrf2 regulates oxidative stress, which is essential for cellular function. Fundamental initiation of Nrf2 in many malignancies increases prosurvival genes & endorses tumour cell propagation via metabolic reprogramming, suppression of tumour programmed cell death, & increased cancer stem cell self-renewal potential. More specifically, Nrf2 has been associated with cancer cell chemoresistance, radioresistance & inflammation-induced carcinogenesis.  METHODS AND RESULTS: Many Nrf2 inhibitors have been revealed for tumour treatment and targeting Nrf2 could be an effective cancer therapeutic method. Before spreading, cancer cells adapt to their surroundings. Cancer cells usually have mutations in tumor suppressor genes. In a variety of malignancies, somatic mutations & other anomalies in the Nrf2 genes, as well as renowned cancer suppressor genes including TP53, CDKN2A, PTEN & PIK3CA, have been found. In tumour cells, somatic mutations in the Nrf2 genes, as well as additional mechanisms that affect Nrf2 binding, and produce aberrant Nrf2 activation. Uncontrolled Nrf2 causes tumour cells to become resistant to antineoplastic drugs & reactive oxygen species (ROS), as well as guiding them toward metabolic reprogramming.  CONCLUSIONS: As a result, Nrf2 has been studied as potential malignancy treatment target. We covered the pathways, mechanisms, and dual characteristics of Nrf2 in malignancy in this article. We also discussed how Nrf2 inhibitors are targeted against cancer in this review.

Role of STAT3 in the initiation, progression, proliferation and metastasis of breast cancer and strategies to deliver JAK and STAT3 inhibitors.

INTRODUCTION: Breast cancer (BC) accounts for the majority of cancers among the female population. Anomalous activation of various signaling pathways has become an issue of concern. The JAK-STAT signaling pathway is activated in numerous cancers, including BC. STAT3 is widely involved in BCs, as 40 % of BCs display phosphorylated STAT3. JAK-STAT signaling is crucial for proliferation, survival, metastasis and other cellular events associated with the tumor microenvironment. Hence, targeting this pathway has become an area of interest among researchers. KEY FINDINGS: This review article focuses on the role of STAT3 in the initiation, proliferation, progression and metastasis of BC. The roles of various phytochemicals, synthetic molecules and biologicals against JAK-STAT and STAT3 in various cancers have been discussed, with special emphasis on BC. SIGNIFICANCE: JAK and STAT3 are involved in various phases from initiation to metastasis, and targeting this pathway is a promising approach to inhibit the various stages of BC development and to prevent metastasis. A number of phytochemicals and synthetic and biological molecules have demonstrated potential inhibitory effects on JAK and STAT3, thereby paving the way for the development of better therapeutics against BC.

Role of Nrf2 Signaling Cascade in Breast Cancer: Strategies and Treatment.

Breast cancer is the second leading cancer among all types of cancers. It accounts for 12% of the total cases of cancers. The complex and heterogeneous nature of breast cancer makes it difficult to treat in advanced stages. The expression of various enzymes and proteins is regulated by several molecular pathways. Oxidative stress plays a vital role in cellular events that are generally regulated by nuclear factor erythroid 2-related factor 2 (Nrf2). The exact mechanism of Nrf2 behind cytoprotective and antioxidative properties is still under investigation. In healthy cells, Nrf2 expression is lower, which maintains antioxidative stress; however, cancerous cells overexpress Nrf2, which is associated with various phenomena, such as the development of drug resistance, angiogenesis, development of cancer stem cells, and metastasis. Aberrant Nrf2 expression diminishes the toxicity and potency of therapeutic anticancer drugs and provides cytoprotection to cancerous cells. In this article, we have discussed the attributes associated with Nrf2 in the development of drug resistance, angiogenesis, cancer stem cell generation, and metastasis in the specific context of breast cancer. We also discussed the therapeutic strategies employed against breast cancer exploiting Nrf2 signaling cascades.

Structure-based virtual screening, molecular dynamics simulation and in vitro evaluation to identify inhibitors against NAMPT.

Nicotinamide phosphoribosyltransferase (NAMPT) is a bottleneck enzyme that plays a key role in recycling nicotinamide to maintain the adequate NAD + level inside the cell. It involves maintaining the cellular bioenergetics and providing a necessary substrate for functions essential to rapidly proliferating the cancer cells. Therefore, inhibition of NAMPT appears as a therapeutic potential for cancer treatment. Here, the vast virtual screening followed by focused docking and in-vitro analysis was carried out to identify the promising hits of NAMPT. We have identified two potential hits from the filtered molecules, which are chemically diverse and have shown comparable quantitative values with reported co-crystal '1QS' as their binding pattern matched nicely. These two compounds are further explored through molecular dynamics simulations (MD) combined with pharmacokinetics profiling and thermodynamic analysis demonstrating their suitability as novel NAMPT inhibitors that can be used as starting points for a hit-to-lead campaign.Communicated by Ramaswamy H. Sarma.

Prognostic value of GRACE score for in-hospital and 6 months outcomes after non-ST elevation acute coronary syndrome.

BACKGROUND: The aim of this study was to determine the predictive value of the Global Registry of Acute Coronary Events (GRACE) score for predicting in-hospital and 6 months mortality after non-ST elevation acute coronary syndrome (NSTE-ACS). RESULTS: In this observational study, 300 patients with NSTE-ACS of age more than 30 years were included; 16 patients died during the hospital stay (5.3%). Of 284 patients at 6 months assessment, 10 patients died (3.5%), 240 survived (84.5%), and 34 were lost to follow-up (12%) respectively. In high risk category, 10.5% of the patients died within hospital stay and 11.8% died within 6 months (p = 0.001 and p = 0.013). In univariate analysis, gender, diabetes mellitus, family history, smoking, and GRACE score were significantly associated with in-hospital mortality whereas age, obesity, dyslipidemia, and GRACE were significantly associated with 6 months mortality. After adjustment, diabetes mellitus, family history, and GRACE score remained significantly associated with in-hospital mortality (p ≤ 0.05) and age remained significantly associated with 6 months mortality. CONCLUSION: GRACE risk score has good predictive value for the prediction of in-hospital mortality and 6 months mortality among patients with NSTE-ACS.

Design and evaluation of cabazitaxel loaded NLCs against breast cancer cell lines.

Cabazitaxel (CBZ) is a taxane derivative and an anti-microtubule agent effective against numerous cancers including drug-resistant cancers. In this study, CBZ loaded nanostructured lipid carriers (NLCs) were prepared by using Design-Expert (DoE) and optimized for various formulation parameters (ratio of lipids and surfactant concentration, homogenization speed and time). The optimized CBZ loaded NLCs formulation was characterized and evaluated through multiple physicochemical characterization techniques like FTIR, DSC, PXRD, SEM and in-vitro drug release. FTIR and DSC results suggested that NLCs entrapped drug inside and had no chemical bonding between drug and NLCs. SEM analysis confirmed homogeneous, spherical, and uniformly distributed NLCs. In-vitro cell culture studies suggested that CBZ loaded NLCs produced ∼ 6- and 2.5-times higher cytotoxicity against MDA-MB-468 and MCF-7 cell lines, respectively compared to pure drug. Cellular uptake of NLC was ∼2.5 and 2.1-fold higher than CBZ alone in MDA-MB-468 and MCF-7 cell lines, respectively. Furthermore, CBZ loaded NLCs produced significantly higher apoptosis and inhibited the mobility of MDA-MB-468 and MCF-7 cells. The results from this study demonstrate the utility of CBZ loaded NLCs as an effective treatment against breast cancer and NLCs as effective drug carriers to deliver the highly lipophilic drug such as CBZ.

Risk Factors Associated With Contrast-Induced Nephropathy after Primary Percutaneous Coronary Intervention.

Background Contrast-induced nephropathy (CIN) after primary percutaneous coronary intervention (PCI) is associated with increased mortality and morbidity. The aim of this study is to determine the frequency of CIN after primary PCI and its association with risk factors in patients with ST-segment elevation myocardial infarction (STEMI) at a tertiary care cardiac center in Pakistan. Methodology In this observational study, we included 282 patients who presented with STEMI and underwent primary PCI at the National Institute of Cardiovascular Disease, Karachi, Pakistan, from October 2017 to April 2018. The serum creatinine (mg/dL) levels were obtained at baseline and 48 to 72 hours after the primary PCI procedure, and patients with a 25% increase or ≥ 0.5 mg/dL rise in post-procedure creatinine level (after 48 to 72 hour) were categorized for CIN. Results Out of a total sample of 282 patients, 68.4% (193) were males, and the mean age was 56.4 ± 9.1 years. A majority of the patients, 78.7% (222), were hypertensive and 34% (96) were diabetic. The CIN was observed in 13.1% (37) of the patients, and increased risk of CIN was found to be associated with the presence of diabetes mellitus and increased (>200 mL) use of contrast during the procedure, with odds ratios of 2.3 (1.14-4.63) and 3.12 (1.36-7.17), respectively. Conclusions The CIN after PCI is a common complication associated with the presence of diabetes mellitus and the use of an increased amount of contrast during the procedure.

A review of nanotechnology-based approaches for breast cancer and triple-negative breast cancer.

Breast cancer (BC) is one of the most prevalent cancers in women. Triple-negative breast cancer (TNBC) in which the three major receptors i.e. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are absent is known to express the most aggressive phenotype and increased metastasis which results in the development of resistance to chemotherapy. It offers various therapeutic advantages in treating BC and TNBC. Nanotechnology offers various unique characteristics such as small size (nanometric), active and passive targeting, and the ability to attach multiple targeting moieties, controlled release, and site-specific targeting. This review focuses on conventional drug therapies, recent treatment strategies, and unique therapeutic approaches available for BC and TNBC. The role of breast cancer stem cells in the recurrence of BC and TNBC has also been highlighted. Several chemotherapeutic agents delivered using nanocarriers such as polymeric nanoparticles/micelles, metallic/inorganic NPs, and lipid-based NPs (Liposome, solid-lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs)), etc. with excellent responses in the treatment of BC/TNBC along with breast cancer stem cells have been discussed in details. Moreover, the application of nanomedicine including CRISPR nanoparticle, exosomes for the treatment of BC/TNBC and other molecular targets available such as poly (ADP-ribose) polymerase (PARP), epidermal growth factor receptor (EGFR), Vascular endothelial growth factor (VEGF), etc. for further exploration have also been discussed.

Lactoferrin Coupled Lower Generation PAMAM Dendrimers for Brain Targeted Delivery of Memantine in Aluminum-Chloride-Induced Alzheimer's Disease in Mice.

Lower generation PAMAM dendrimers have an immense potential for drug delivery with lower toxicity, but these dendrimers yet need certain basic ameliorations. In this study, the brain delivery potential of the synthesized PAMAM-Lf (lower generation PAMAM and lactoferrin conjugate) loaded with memantine (MEM) was explored and evaluated in vitro and in vivo in the disease-induced mouse model. The developed nanoscaffolds were characterized for size, zeta potential and in vitro release. Increase in the average size from 11.54 ± 0.91 to 131.72 ± 4.73 nm, respectively, was observed for drug-loaded PAMAM (i.e., PAMAM-MEM) and PAMAM-Lf (i.e., MEM-PAMAM-Lf).  Release profile of MEM from MEM-PAMAM-Lf was slow and sustained up to 48 h. In vivo biodistribution in the Sprague-Dawley rat model revealed that the brain uptake of MEM-PAMAM-Lf was significantly higher than that of MEM alone. The behavioral response study in the healthy rats did not result in any significant changes. The in vivo study in an AlCl3-induced Alzheimer's (AD) mice model showed a significant improvement in behavioral responses. Optical density, which reflects the acetylcholinesterase (AChE) activity, was highest in the AL group 0.16 ± 0.01 (higher than the CON group, 0.09 ± 0.02; p < 0.05). No significant suppression of AChE activity was recorded in all the other treated groups. Similarly, the DOPAmine and 3,4 dihydroxyphenylacetic acid (DOPAC) levels were unaffected by the developed formulations. The study reported improved brain bioavailability of MEM in AlCl3-induced Alzheimer's mice leading to improved memory, with the resultant mechanism behind in a descriptive manner. This study is among the preliminary studies reporting the memory improvement aspect of PAMAM-Lf conjugates for MEM in AlCl3-AD induced mice. The formulation developed was beneficial in AD-induced mice and had a significant impact on the memory aspects.

The autoimmune basis of hypopituitarism in traumatic brain injury: fiction or reality?

Post-traumatic hypopituitarism has remained as an obscured cause of worsening morbidity and mortality in head injury patients. Researchers have for decades been puzzled by the mechanism of pituitary dysfunction in these cases. Amongst other causes like direct injury, vascular injury etc, an immunological basis of hypopituitarism has been suggested in some animal studies as well as human research. In this article, we have reviewed the latest articles and compiled the evidence which suggests for or against the role of autoimmunity in post-traumatic hypopituitarism or which defines the strength to which autoimmunity has been established as a cause of head-injury induced pituitary dysfunction.

Polymeric Nanocarriers: A New Horizon for the Effective Management of Breast Cancer.

BACKGROUND: Delivery of chemotherapeutic drugs for the diagnosis and treatment of cancer is becoming advanced day by day. However, the challenge of the effective delivery system still does exist. In various types of cancers, breast cancer is the most commonly diagnosed cancer among women. Breast cancer is a combination of different diseases. It cannot be considered as only one entity because there are many specific patient factors, which are involved in the development of this disease. Nanotechnology has opened a new area in the effective treatment of breast cancer due to the several benefits offered by this technology. METHODS: Polymeric nanocarriers are among one of the effective delivery systems, which has given promising results in the treatment of breast cancers. Nanocarriers does exert their anticancer effect either through active or passive targeting mode. RESULTS: The use of nanocarriers has been resolute about the adverse effects of chemotherapeutic drugs such as poor solubility and less penetrability in tumor cells. CONCLUSION: The present review is focused on recent developments regarding polymeric nanocarriers, such as polymeric micelles, polymeric nanoparticles, dendrimers, liposomes, nanoshells, fullerenes, carbon nanotubes (CNT) and quantum dots, etc. for their recent advancements in breast cancer therapy.