Miniaturizing in chip technology, optics, micro mechanics, medicine, gene and biotechnology requires highly precise positioning techniques. The motivation for the new manipulation technology is the desire to enter the micro- and nanoworld not only by viewing but also acting, altering micro- and nanosized objects. A new era on medicine are expected to happen in the coming years. Due to the advances in the field of nanotechnology, nanodevice manufacturing has been growing gradually. From such achievements in nanotechnology and recent results in biotechnology and genetics, the first operating biological nanorobots are expected to appear in the coming 5 years and more complex diamondoid based nanorobots will become available in about 10 years. In terms of time, it means a very near better future with significant improvements in medicine.
Abstract:The purpose of this research was to develop a matrix-type transdermal therapeutic system containing drug Aceclofenac with different ratios of hydrophilic (hydroxyl propyl cellulose) and hydrophobic (ethyl cellulose) polymeric systems by the solvent evaporation technique by using 15 % w/w of dibutyl phthalate to the polymer weight, incorporated as plasticizer. Different concentrations of oleic acid and isopropyl myristate were used to enhance the transdermal permeation of Aceclofenac. The physicochemical compatibility of the drug and the polymers studied by differential scanning calorimetry and infrared spectroscopy suggested absence of any incompatibility. Formulated transdermal films were physically evaluated with regard to thickness, weight variation, drug content, flatness, tensile strength, folding endurance, percentage of moisture content and water vapour transmission rate. All prepared formulations indicated good physical stability. In-vitro permeation studies of formulations were performed by using Franz diffusion cells. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in-vitro skin permeation through rat skin (Wistar albino rat) as compared to all other formulations. The results followed the release profile of Aceclofenac followed mixed zero-order and first-order kinetics in different formulation. However, the release profile of the optimized formulation F9 (r 2 = 0.9935 for Higuchi) indicated that the permeation of the drug from the patches was governed by a diffusion mechanism. Formulation F9 showed highest flux among all the formulations and 1.369 fold enhancements in drug permeation. These results indicate that the formulation containing 15 % of oleic acid with 10 % Isopropyl myristate give better penetration of Aceclofenac through rat skin.
Nanohydrogel combines the advantages of hydrogel and nano particulate systems. Similar to the hydrogel and macrogel, nanohydrogel can protect the drug and control drug release by stimuli responsive conformation or biodegradable bond into the polymer networks. Nanohydrogel has drawn huge interest due to their potential applications, such as carrier in target-specific controlled drug delivery, absorbents, chemical/biological sensors, and bio-mimetic materials. Similar to the nanoparticles, stimuli responsive nanohydrogel can easily be delivered in the liquid form for parenteral drug delivery application. This review highlights the methods to prepare nanohydrogel based on natural and synthetic polymers for diverse applications in drug delivery. It also encompasses the drug loading and drug release mechanism of the nanohydrogel formulation and patents related to the composition and chemical methods for preparation of nanohydrogel formulation with current status in clinical trials.
With the continuous emergence of SARS-CoV-2 variants of concern and implementation of mass-scale interventions like vaccination, understanding factors affecting disease transmission has critical implications for control efforts. Here we used a simple adapted N95 mask sampling method to demonstrate the impact of circulating SARS-CoV-2 variants and vaccination on 92 COVID-19 patients to expel virus into the air translating to a transmission risk. Between July and September 2021, when the Delta was the dominant circulating strain in Mumbai, we noted a two-fold increase in the proportion of people expelling virus (95%), about an eighty-fold increase in median viral load and a three-fold increase in high emitter type (41%; people expelling >1000 viral copy numbers in 30 minutes) compared to initial strains of 2020. Eight percent of these patients continued to be high emitters even after eight days of symptom onset, suggesting a probable increased transmission risk for Delta strain even at this stage. There was no significant difference in expelling pattern between partial, full and un-vaccinated individuals suggesting similar transmission risk. We noted significantly more infections among vaccinated study patients and their household members than unvaccinated, probably due to increased duration from vaccination and/or increased risk behaviour upon vaccination due to lower perceived threat. This study provides biological evidence for possible continued transmission of the Delta strain even with vaccination, emphasizing the need to continue COVID-19 appropriate behaviour. The study also indicates that the mask method may be useful for screening future vaccine candidates, therapeutics or interventions for their ability to block transmission.
Universal access to drug susceptibility testing for newly diagnosed tuberculosis patients is recommended. Access to culture-based diagnostics remains limited, and targeted molecular assays are vulnerable to emerging resistance mutations.
Background: The purpose of this study was to formulate, characterize and conduct in vitro cytotoxicity of 5-fluorouracil loaded polymeric electrospun nanofibers for the treatment of skin cancer. The patents on electrospun nanofibers (US9393216B2), (US14146252), (WO2015003155A1) etc. helped in the selection of polymers and method for the preparation of nanofibers. Methods: In the present study, the fabrication of nanofibers was done using a blend of chitosan with polyvinyl alcohol and processed using the electrospinning technique. 5-fluorouracil with known chemotherapeutic potential in the treatment of skin cancer was used as a drug carrier. 24-1 fractional factorial screening design was employed to study the effect of independent variables like the concentration of the polymeric solution, applied voltage (kV), distance (cm), flow rate (ml / hr) on dependent variables like % entrapment efficiency and fiber diameter. Results: Scanning electron microscopy was used to characterize fiber diameter and morphology. Results showed that the fiber diameter of all batches was found in the range of 100-200 nm. The optimized batch results showed the fiber diameter of 162.7 nm with uniform fibers. The tensile strength obtained was 190±37 Mpa. Further in vitro and ex vivo drug release profile suggested a controlled release mechanism for an extended period of 24 hr. The 5-fluorouracil loaded electrospun nanofibers were found to decrease cell viability up to ≥50% over 24 hr, with the number of cells dropping by ~ 10% over 48 hr. As the cell viability was affected by the release of 5-fluorouracil, we believe that electrospun nanofibers are a promising drug delivery system for the treatment of Basal Cell Carcinoma (BCC) skin cancer. Conclusion: These results demonstrate the possibility of delivering 5-Fluorouracil loaded electrospun nanofiber to skin with enhanced encapsulation efficiency indicating the effectiveness of the formulation for the treatment of basal cell carcinoma type of skin cancer.
The present study was initiated to understand the proportion of predominant variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in postvaccination infections during the Delta dominated second wave of coronavirus disease 2019 (COVID-19) in the Mumbai Metropolitan Region (MMR) in India and to understand any mutations selected in the postvaccination infections or showing association with any patient demographics. Samples were collected (n = 166) from severe/moderate/mild COVID-19 patients who were either vaccinated (COVISHIELD/COVAXIN-partial/fully vaccinated) or unvaccinated, from a city hospital and from home isolation patients in MMR. A total of 150 viral genomes were sequenced by Oxford Nanopore sequencing and the data of 136 viral genomes were analyzed for clade/lineage and for identifying mutations. The sequences belonged to three clades (21A, 21I, and 21J) and their lineage was identified as either Delta (B.1.617.2) or Delta+ (B.1.617.2 + K417N) or sub-lineages of Delta variant (AY.120/AY.38/AY.99). A total of 620 mutations were identified of which 10 mutations showed an increase in trend with time (May-October 2021). Associations of six mutations (two in spike, three in orf1a, and one in nucleocapsid) were shown with milder forms of the disease and one mutation (in orf1a) with partial vaccination status. The results indicate a trend toward reduction in disease severity as the wave progressed.
Systemic chemotherapy has been shown to produce side effects. A small fraction of the drug reaches the tumor site; other healthy organs or normal tissues get affected or damaged due to the nonspecific action of these cytotoxic agents. Furthermore, due to their short period of activity, repeat injections are often required, which can lead to the exacerbation of side effects and inconvenience. To overcome these obstacles, in this study, we developed controlled and targeted intratumoral injection. Hydrogel was prepared by physical cross-linking method; however, nanohydrogel was prepared using tip probe-sonicator method. Our results revealed that biodegradable and thermosensitive 5-fluorouracil-loaded methylcellulose nanohydrogel synthesized by physical cross-linking method may be a beneficial approach in targeting the therapeutic agent to the tumor site.
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