Microneedles of chitosan-porous carbon nanocomposites: Stimuli (pH and electric field)-initiated drug delivery and toxicological studies.

An array of microneedles (MNs) of chitosan-graphene assembled in porous carbon (CS-GAPC) nanocomposites has been synthesized and evaluated. The safety of the formulated system has been ensured using detailed in vivo toxicological studies and efficacy has been ensured by evaluating the stimuli (pH and electric field) initiated drug delivery properties. Drug cephalexin has been incorporated in these MNs. In vivo toxicological studies of CS-GAPC nanocomposite were performed on Sprague rats, using acute dermal and subacute dermal (ADT& SADT) test, histopathological studies, biochemical studies, and AMES tests. ADT and SADT studies showed that median lethal dose (LD50 ) was found greater than 2000 mg/kg body weight; with no abnormal weight gain and food consumption, during the study period of 28 days. This study showed that administration of CS-GAPC did not cause any substantial alterations in hematological and biochemical parameters of the animals. Histopathological studies showed no significant changes in the control and CS-GAPC administered groups. AMES tests reveal that CS-GAPC nanocomposite is nonmutagenic against the Salmonella thyphimurium strains. No abnormalities were observed in the animal's chromosomal aberrations and clastogenic values when the animals were treated with CS-GAPC. At acidic pH of 4, the encapsulated drug was completely released, indicating that the drug release from the prepared nanocomposite is pH dependent. An electric field of 5 V showed optimum drug release, as a function of applied electric pulses. A biologically safe drug encapsulation model system is hence projected for smart drug delivery (pH dependent and electric field triggered) using the microneedle approach. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1582-1596, 2019.

Pullulan-histone antibody nanoconjugates for the removal of chromatin fragments from systemic circulation.

The billions of cells that die in the adult human body daily release considerable amounts of fragmented chromatin in the form of mono- and oligonucleosomes into the circulation in normal individuals, and in higher quantities in many disease conditions. Recent results suggest that circulating chromatin fragments (Cfs) especially from abnormal cells can spontaneously enter into healthy cells to damage their DNA and induce genomic instability. Furthermore, Cfs isolated from cancer patients may induce oncogenic transformation in the recipients' cells. Thus, it follows that if such Cfs emanating from apoptotic cells could be prevented from reaching other cells, it could potentially inhibit pathological conditions, including cancer. Here we have developed pullulan based histone antibody nanoconjugates for the removal of Cfs. Nanoconjugates were developed and various physico-chemical characterizations were carried out. The efficacy of these nanoconjugates on removing Cfs was evaluated both in vitro and in vivo. Our results indicate that nanoconjugates may have therapeutic value in the efficient removal of Cfs, reducing inflammation and fatality in a mouse model of sepsis, and in preventing neutropenia following treatment with Adriamycin.

Bacopa monnieri and L-deprenyl differentially enhance the activities of antioxidant enzymes and the expression of tyrosine hydroxylase and nerve growth factor via ERK 1/2 and NF-κB pathways in the spleen of female wistar rats.

Aging is characterized by development of diseases and cancer due to loss of central and peripheral neuroendocrine-immune responses. Free radicals exert deleterious effects on neural-immune functions in the brain, heart, and lymphoid organs and thus, affecting the health. Bacopa monnieri (brahmi), an Ayurvedic herb, and L-deprenyl, a monoamine oxidase-B inhibitor, have been widely used in the treatment of neurodegenerative diseases. The purpose of this study was to investigate whether brahmi (10 and 40 mg/kg BW) and deprenyl (1 and 2.5 mg/kg BW) treatment of 3-month old female Wistar rats for 10 days can modulate the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)] in the brain and spleen. In addition, the effects of these compounds on the expression of tyrosine hydroxylase (TH), nerve growth factor (NGF), the intracellular signaling markers, p-ERK1/2, p-CREB, and p-NF-kB, and nitric oxide (NO) production were measured in the spleen by Western blot analysis. Both brahmi and deprenyl enhanced CAT activity, and p-TH, NGF, and p-NF-kB expression in the spleen. However, deprenyl alone was found to enhance the p-ERK1/2 and p-CREB expression in the spleen. The activities of SOD, CAT, and GPx in the thymus, mesenteric lymph nodes, heart, and brain areas (frontal cortex, medial basal hypothalamus, striatum, and hippocampus) were differentially altered by brahmi and deprenyl. Brahmi alone enhanced NO production in the spleen. Taken together, these results suggest that both brahmi and deprenyl can protect the central and peripheral neuronal systems through their unique effects on the antioxidant enzyme activities and intracellular signaling pathways.