NON INVASIVE DELIVERY OF PROTEIN AND PEPTIDE DRUGS: A REVIEW

Till recent, injections remained the most common route for administration of protein and peptide drugs because of their poor bioavailability in the other routes. Because it is generally recognized that injection based delivery is a major impediment to the commercial success of therapeutic proteins and peptides, research in both academia and industry continues to focus on ways to overcome this problem. Possible non-parenteral administration routes for delivery of peptide and protein drugs include oral, nasal, ocular, transdermal, rectal, colonic, and vaginal route. The large surface area associated with most of these routes makes them attractive targets for drug delivery. While non-invasive administration by these routes is considered a more logical and achievable option for local treatment regimens, systemic delivery of proteins and peptides is significantly more challenging. In spite of effort made on the development of drugs for these routes, most of the successes fail to address how the technology will be transformed to a commercial product. The only notable exceptions have been the successful commercialization of nasal formulations for systemic delivery of a limited number of therapeutic peptides, and recent regulatory approvals of both pulmonary and buccal delivery systems for systemic delivery of insulin and an oral formulation of a small peptide analog, cyclosporine, have been commercialized. The present review aims to discuss the potential non-invasive routes of protein and peptide drug delivery. The factors which will affect drug transport and the bioavailability of proteins administered through these routes is also emphasize

UV SPECTROPHOTOMETRIC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF ALPRAZOLAM AND MEBEVERINE HYDROCHLORIDE IN BULK DRUG AND PHARMACEUTICAL FORMULATION

A simple, accurate, precise, sensitive, rapid and economical spectrophotometric method was developed and validated for simultaneous estimation of Alprazolam (ALP) and Mebeverine HCl (MBH) in bulk drug and pharmaceutical formulation. The estimation of these drugs was carried out by using 0.1M HCl as a solvent. The wavelength maxima for Alprazolam and Mebeverine HCl were found to be 262.3 nm and 222.5 nm. The linearity range was observed in the concentration range of 3-15 µg/ml for both drugs and regression equation was found to be for ALP 0.0565x+0.0138 and for MBH 0.049x-0.0126. Percentage recoveries for Alprazolam and Mebeverine HCl were found to be 99.84% and 99.47% respectively. % RSD values for Intra-day precision were found to be for ALP 1.18% and for MBH 0.59%. Inter-day precision %RSD values were found to be for ALP 0.94% and for MBH 0.69%. LOD was found to be for ALP 1.42 (µg/ml) and for MBH 2.1542 (µg/ml). LOQ was found to be for ALP 4.3242 (µg/ml) and for MBH 6.5442 (µg/ml). The %Assay of Alprazolam and Mebeverine HCl were found to be 99.20% and 100.02% respectively. Statistical analysis proved that the developed method can be successfully used for simultaneous analysis of Alprazolam and Mebeverne HCl in pure and tablet dosage forms

Design And Implementation Of High Security Banking System By Using Iot Technology

This project focuses on designing and also creating biometric finger print modern technology based loan deal system for buying. As even more worldwide financial activity comes to be digitally-based, financial institutions are utilizing brand-new technologies to create next-generation identification controls to deal with fraud, make purchases much safer, and also boost the client experience. The sensing unit is a solid-state finger print sensing unit that dependably catches fingerprint info. It is created to integrate right into devices for enhanced safety as well as convenience. The sensing unit supplies a dependable, fast and also easy to use option to passwords, PIN's and other forms of individual verification. Individual need not lug any kind of physical cards (credit score, debit and so on) or cell phones for money transaction. Individual simply need to keep finger print go into purchase amount using keypad. This purchase details is sent to server over safe IoT (WiFi) and more processing done there. If the deal achieves success then individual obtains SMS confirmation message to his registered telephone number. This onboard computer includes number of input as well as outcome ports. The onboard computer system is generally termed as micro controller. The input and also output port of the micro controller are interfaced with various input and output modules depending on the demands. In other words micro controller works as a communication medium for all the components involved in the job. The tool likewise includes GSM modem, Wi-fi components, Keypad, LCD which presents the information regarding purchases

FABRICATION AND CHARACTERIZATION OF FAST DISSOLVING FILMS OF ECLIPTA PROSTRATE LEAVES EXTRACT TO TREAT MOUTH ULCERS

Objective: This research focused on the design of fast dissolving herbal film of Eclipta Prostrate leaves extract for mouth ulcers. Methods: The extract of Eclipta Prostrata leaves was formulated as films by solvent casting method using various polymers viz., HPMC E5, HPMC E15, sodium alginate and PVA. The films were designed by using propylene glycol as a plasticizer, SSG as super disintegrate and honey as a sweetener. Furthermore, the films were evaluated for thickness, folding endurance, weight variation, % elongation, surface pH, % moisture uptake, % moisture loss, disintegration and in vitro drug release study. Results: The revealed that all the films were good in appearance and had a smooth texture. Out of all ten formulations, F3 and F5 disintegrated rapidly with a disintegration time of 27 and 32 seconds. The drug release studies revealed that all the formulations had a good release profile, but the F3 formulation showed rapid release i.e. 83.57% in 4 min. The stability studies revealed that the formulations F3 and F5 were found good with non-tackiness, easily separable and disintegrated at 29 and 33 sec respectively with no appearance and drug release. Conclusion: The research revealed that Eclipta prostrate leaves extract can be formulated into oral films for the treatment of mouth ulcers with improved bioavailability and expected patient compliance

Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological hallmarks including β-amyloid (Aβ) accumulation, oxidative stress, and apoptotic cell death. The causes of AD and AMD are likely multi-factorial with several factors such as diet, environment, and genetic susceptibility participating in the pathogenesis of these diseases. Epidemiological studies correlated high plasma cholesterol levels with high incidence of AD, and feeding rabbits with a diet rich in cholesterol has been shown to induce AD-like pathology in rabbit brain. High intake of cholesterol and saturated fat were also long been suspected to increase the risk for AMD. However, the extent to which cholesterol-enriched diet may also cause AMD-like features in rabbit retinas is not well known.</p> <p>Methods</p> <p>Male New Zealand white rabbits were fed normal chow or a 2% cholesterol-enriched diet for 12 weeks. At necropsy, animals were perfused with Dulbecco's phosphate-buffered saline and the eyes were promptly removed. One eye of each animal was used for immunohistochemistry and retina dissected from the other eye was used for Western blot, ELISA assays, spectrophotometry and mass spectrometry analyses.</p> <p>Results</p> <p>Increased levels of Aβ, decreased levels of the anti-apoptotic protein Bcl-2, increased levels of the pro-apoptotic Bax and gadd153 proteins, emergence of TUNEL-positive cells, and increased generation of reactive oxygen species were found in retinas from cholesterol-fed compared to normal chow-fed rabbits. Additionally, astrogliosis, drusen-like debris and cholesterol accumulations in retinas from cholesterol-fed rabbits were observed. As several lines of evidence suggest that oxidized cholesterol metabolites (oxysterols) may be the link by which cholesterol contributes to the pathogenesis of AMD, we determined levels of oxysterols and found a dramatic increase in levels of oxysterols in retinas from cholesterol-fed rabbits.</p> <p>Conclusions</p> <p>Our results suggest that cholesterol-enriched diets cause retinal degeneration that is relevant to AMD. Furthermore, our data suggests high cholesterol levels and subsequent increase in the cholesterol metabolites as potential culprits to AMD.</p

Seroprevalence of syphilis in human immunodeficiency virus patients

Background: Syphilis is a sexually transmitted infection caused by, Treponema pallidum. Syphilis facilitates the transmission and acquisition of human immunodeficiency virus (HIV) and causes transient increase in the viral load. Sexually transmitted infections (STI) are 3-5 times more likely to acquire HIV infection, if exposed to the virus through sexual contact. Aim of the study was to estimate the seroprevalence of Syphilis in HIV patients.Methods: A total of 920 blood samples were collected from HIV patients attending ART (Antiretroviral therapy) centre and were tested for Syphilis by using Rapid Plasma Reagin (RPR) and Treponema pallidum Hemagglutination Assay (TPHA). A total of 100 HIV non-reactive individuals were taken as a control group.Results: Out of 920 samples, 102 (11.1%) were positive for Syphilis. Out of 102 Syphilis seropositive patients, males (76.5%) were more commonly affected in age group of 21-40 years. Both RPR and TPHA were reactive in 46% of cases and only TPHA reactive in 53.9% of cases. Out of 100 HIV non-reactive patients, 5% of patients are reactive for Syphilis.Conclusions: In the present study, prevalence of Syphilis was more in HIV patients compared to HIV non-reactive persons. Persons with HIV infection acquired through sexual route should be screened for Syphilis by one nonspecific test along with specific test to confirm the diagnosis. This will help in proper management of the patients having Syphilis and HIV co-infection

Unilateral hemothorax in a 46 year old South Indian male due to a giant arteriovenous hemodialysis fistula: a case report

In a patient undergoing regular hemodialysis through an arteriovenous fistula access, pleural effusion is a known long term complication. However, a unilateral hemothorax is relatively uncommon. Here we report a 46 year old male, end-stage renal disease patient, on maintenance hemodialysis, who presented with a giant brachiocephalic AV fistula in his left arm and progressive breathlessness. Radiological imaging revealed a left sided pleural effusion. Ultrasound guided aspiration revealed a hemorrhagic pleural fluid. A Doppler study of the fistula revealed a high velocity blood flow through the fistula, thereby establishing the cause of the unilateral hemothorax. Ligation of the fistula resulted in complete resolution of the hemothorax. The other possible causes for hemothorax in a dialysis patient are also discussed in this case report

Oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes exposed to clomazone (in vitro)

The aim of this study was to investigate the effect of clomazone herbicide on oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes in in vitro conditions. The activity of catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE), as well as the levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were measured in human erythrocytes exposed (in vitro) to clomazone at varying concentrations in the range of 0, 100, 250 and 500 µg/L for 1 h at 37 °C.TBARS levels were significantly higher in erythrocytes incubated with clomazone at 100, 250 and 500 µg/L. However, erythrocyte CAT and AChE activities were decreased at all concentrations tested. SOD activity was increased only at 100 µg/L of clomazone. GSH levels did not change with clomazone exposure. These results clearly showed clomazone to induce oxidative stress and AChE inhibition in human erythrocytes (in vitro). We, thus, suggest a possible role of ROS on toxicity mechanism induced by clomazone in humans

The oxysterol 27-hydroxycholesterol increases β-amyloid and oxidative stress in retinal pigment epithelial cells

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological features including β-amyloid (Aβ) peptide accumulation, oxidative damage, and cell death. The causes of AD and AMD are not known but several studies suggest disturbances in cholesterol metabolism as a culprit of these diseases. We have recently shown that the cholesterol oxidation metabolite 27-hydroxycholesterol (27-OHC) causes AD-like pathology in human neuroblastoma SH-SY5Y cells and in organotypic hippocampal slices. However, the extent to which and the mechanisms by which 27-OHC may also cause pathological hallmarks related to AMD are ill-defined. In this study, the effects of 27-OHC on AMD-related pathology were determined in ARPE-19 cells. These cells have structural and functional properties relevant to retinal pigmented epithelial cells, a target in the course of AMD.</p> <p>Methods</p> <p>ARPE-19 cells were treated with 0, 10 or 25 μM 27-OHC for 24 hours. Levels of Aβ peptide, mitochondrial and endoplasmic reticulum (ER) stress markers, Ca²⁺homeostasis, glutathione depletion, reactive oxygen species (ROS) generation, inflammation and cell death were assessed using ELISA, Western blot, immunocytochemistry, and specific assays.</p> <p>Results</p> <p>27-OHC dose-dependently increased Aβ peptide production, increased levels of ER stress specific markers caspase 12 and gadd153 (also called CHOP), reduced mitochondrial membrane potential, triggered Ca²⁺dyshomeostasis, increased levels of the nuclear factor κB (NFκB) and heme-oxygenase 1 (HO-1), two proteins activated by oxidative stress. Additionally, 27-OHC caused glutathione depletion, ROS generation, inflammation and apoptotic-mediated cell death.</p> <p>Conclusions</p> <p>The cholesterol metabolite 27-OHC is toxic to RPE cells. The deleterious effects of this oxysterol ranged from Aβ accumulation to oxidative cell damage. Our results suggest that high levels of 27-OHC may represent a common pathogenic factor for both AMD and AD.</p