Omeprazole and PGC-formulated heparin binding epidermal growth factor normalizes fasting blood glucose and suppresses insulitis in multiple low dose streptozotocin diabetes model.

Purpose: Our objective was to develop novel nanocarriers (protected graft copolymer, PGC) that improve the stability of heparin binding EGF (HBEGF) and gastrin and then to use PGC-formulated HBEGF (PGC-HBEGF) and Omeprazole (+/- PGC-gastrin) for normalizing fasting blood glucose (FBG) and improving islet function in diabetic mice.

Methods: HBEGF, PGC-HBEGF, Omeprazole, Omeprazole + PGC-HBEGF, Omeprazole + PGC-gastrin + PGC-HBEGF and epidermal growth factor (EGF) + gastrin were tested in multiple low dose streptozotocin diabetic mice.

Results: Omeprazole + PGC-HBEGF normalized FBG and is better than EGF + gastrin at improving islet function and decreasing insulitis.

Enhanced oral bioavailability of the hydrophobic chemopreventive agent (SR13668) in beagle dogs.

Potency and activity of SR13668 in cancer prevention have been proven in several in vitro and in vivo cancer models. However, the compound is highly hydrophobic and its limited oral bioavailability has hindered its clinical translation. In this study, we encapsulated SR13668 into polymeric nanoparticles to increase compound aqueous solubility and therefore bioavailability.

Protected graft copolymer excipient leads to a higher acute maximum tolerated dose and extends residence time of vasoactive intestinal Peptide significantly better than sterically stabilized micelles.

Purpose: To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoactive Intestinal Peptide (VIP).

Methods: VIP was formulated using a micellar (Sterically Stabilized Micelles, SSM) and a polymer-based (Protected Graft Copolymer, PGC) nanocarrier at various loading percentages. VIP binding to the nanocarriers, pharmacokinetics, blood pressure, blood chemistry, and acute maximum tolerated dose (MTD) of the formulations after injection into BALB/c mice were determined.

Oral toxicity and pharmacokinetic studies of SHetA2, a new chemopreventive agent, in rats and dogs.

SHetA2 is a heteroarotinoid that has shown selective inhibition of cancer cell growth and an induction of apoptosis without activation of nuclear retinoic acid receptors. In the rat study, SHetA2 was administered in 1% aqueous methylcellulose/0.2% Tween 80 by oral gavage at 0, 100, 500, and 2,000 mg/kg/day for 28 days.

Combination treatment with bortezomib and thiostrepton is effective against tumor formation in mouse models of DEN/PB-induced liver carcinogenesis.

Nanoparticle-encapsulated thiazole antibiotic, thiostrepton, has been shown to be an effective agent for inhibiting tumor growth in solid tumor models through the inhibition of proteasomal activity by the induction of apoptosis in cancer cells. Here, we show the efficacy of thiostrepton-micelles in inhibiting tumor growth in a DEN/PB-induced liver cancer model. We also demonstrate an enhanced anticancer effect of the combination treatment of thiostrepton with bortezomib, another proteasome inhibitor in this liver cancer model.

Enhanced oral bioavailability of a cancer preventive agent (SR13668) by employing polymeric nanoparticles with high drug loading.

SR13668 [2,10-Dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3-b)carbazole] has been proven effective in cancer prevention, but the limited bioavailability has hindered its clinical translation. In this study, we have developed a continuous, scalable process to form stable poly(lactic-co-glycolic acid) nanoparticles encapsulating SR13668, based on understanding of the competitive kinetics of nanoprecipitation and spray drying. The optimized formulation achieved high drug loading (33.

Protected graft copolymer (PGC) basal formulation of insulin as potentially safer alternative to Lantus® (insulin-glargine): a streptozotocin-induced, diabetic Sprague Dawley rats study.

Purpose: To develop a long-acting formulation of native human insulin with a similar pharmacodynamics (PD) profile as the insulin analogue insulin glargine (Lantus®, Sanofi-Aventis) with the expectation of retaining native human insulin's superior safety profile as insulin glargine is able to activate the insulin-like growth factor 1 (IGF-1) receptor and is linked to a number of malignancies at a higher rate than regular human insulin.

Methods: Development of protected graft copolymer (PGC) excipients that bind native human insulin non-covalently and testing blood glucose control obtained with these formulations in streptozotocin-induced diabetic Sprague Dawley rats compared to equally dosed insulin glargine.

Results: PGC-formulations of native human insulin are able to control blood glucose to the same extent and for the same amount of time after s.

Detoxification of Nerium indicum roots based on Indian system of medicine: phytochemical and toxicity evaluations.

Indian system of medicine describes the usage of certain very toxic plant based drugs after performing a detoxification process (Shodhana samskara). Nerium indicum is traditionally used as a medicine though known to cause severe allergic symptoms, tachycardia and gastrointestinal effects leading to fatalities. In this study, the detoxification (shodhana) for Nerium indicum was scientifically validated based on phytochemical and toxicity profiles.

Hormonal crosstalk with calcium channel blocker during implantation.

The site specific action of the calcium channel blocker diltiazem in blocking prostaglandin synthesis and hence causing blastocyst implantation failure has been previously described. Based on this understanding it was important to learn if this pathway was under the control of the fine balance in estradiol-progesterone (E2-P4) milieu, considered to be of the utmost significance for effective implantation. In the current study the circulating E2-P4 levels were monitored on the first 6 d of pregnancy at various time points using sensitive chemiluminescence based assays.

Establishing the probable mechanism of L-DOPA in Alzheimer's disease management.

Clinical data suggest the role of L-DOPA in Alzheimer's Disease (AD) though its mechanism of action in AD is not clear. Previous results suggest that L-DOPA might have a complex mixture of pro- and antioxidant effects contributing to tissue damage due to oxidative stress. Furthermore, entacapone, a COMT inhibitor, is known to retain greater levodopa levels in plasma during coadministration.

Role of the calcium channel in blastocyst implantation: a novel contraceptive target.

The proinflammatory blastocyst implantation cascade involves important mediators like prostaglandins (PG). The influx of calcium via the calcium channel acts as a trigger for the activation of the PG synthesis pathway. Hence, it was hypothesized that calcium channel blockers that are known to possess anti-inflammatory activity may interfere with normal implantation.

Cyclooxygenase inhibitors: a novel direction for Alzheimer's management.

Research in Alzheimer's disease (AD) currently includes various cellular, molecular, genetic, clinical and therapeutic approaches. The cytopathological significance of oxidative damage has been studied in neurons of AD patients. Many epidemiological studies suggest that use of non-steroidal anti-inflammatory drugs (NSAIDs) delay or slow the clinical expression of AD, and anti-oxidant properties of NSAIDs have also been previously described.