Conveyance of sofosbuvir through vesicular lipid nanocarriers as an effective strategy for management of viral meningitis.

This study aimed to deliver a potential water-soluble antiviral drug (sofosbuvir) through optimized vesicular lipid nanocarriers (LNs) to the rat brain as a novel strategy against viral meningitis. A 23 factorial design approach was established to assess the effect of formulation composition and process variables on the physicochemical properties of the LNs. Sofosbuvir-loaded LNs (SLNs) were developed by lipid layer hydration method utilizing optimized parameters and evaluated for various in vitro characterizations like FTIR, DSC, XRD, FESEM, vesicle size, zeta potential, drug carrying capacity and drug release. Plasma and brain pharmacokinetic (PK) studies were conducted in Sprague-Dawley rats. FTIR data depicted the absence of any major interaction between the drug and the excipients. DSC revealed a sharp endothermic peak for the drug. XRD showed the amorphic nature of the SLNs. Optimized SLNs were spherical as depicted from FESEM with 42.43 nm size, -49.21 mV zeta potential, 8.31% drug loading and sustained drug release in vitro. Plasma/brain PK studies depicted significant improvement in key PK parameters, viz. AUC, AUMC, MRT, and Vd, compared to those for the free drug. A more than 3.5-fold increase in MRT was observed for optimized SLNs (11.2 h) in brain tissue compared to the free drug (3.7 h). Ex vivo hemolysis data confirmed the non-toxic nature of the SLNs to human red blood cells. In silico docking study further confirmed strong interaction between the drug and selected protein 4YXP (herpes simplex) with docking score of -7.5 and 7EWQ protein (mumps virus) with docking score of -7.3. The optimized SLNs may be taken for further in vivo studies to pave the way towards clinical translation.

A mucoadhesive nanolipo gel containing Aegle marmelos gum to enhance transdermal effectiveness of linezolid for vaginal infection: In vitro evaluation, in vitro-ex vivo correlation, pharmacokinetic studies.

Effective treatment of vaginal infections with conventional antibiotics often faces challenges like unavoidable dose-related side effects with increased risk of bacterial resistance. The study aims to deliver linezolid through natural gum based mucoadhesive nano lipogel to improve therapeutic effectiveness against vaginal infections. The linezolid loaded nanoliposomes (LNLs) were developed by thin film hydration method and were characterized by FTIR, DSC, XRD, FESEM, particle size analysis, zeta potential, drug loading capacity, in vitro release study etc. Selected LNLs was loaded into suitable gel formulation containing Aegle marmelos gum (as the mucoadhesive agent) and evaluated for in vitro, in vivo potentiality. FTIR/DSC test confirmed absence of any major interaction between selected drug and excipients. XRD showed amorphization of the drug encapsulated in NLs. FESEM studies showed spherical LNLs having smooth surface. LNLs had nanosize (51.03 nm), negative surface charge (-25.7 mV), satisfied drug loading capacity (11.5 ± 0.7 %) with sustained drug release. The experimental LNLs loaded lipogel showed desired physico-chemical properties viz. viscosity (37000 cps), spreadability (6.5 gm.cmsec-1), mucoadhesion (21.9 gf) and 61.04 % release of drug across rabbit vaginal mucosal membrane. The nanolipo gel exhibited improved antimicrobial activity against E. coli and C. albicans with respect to the pure linezolid. A good correlation was observed in between in vitro drug release and ex vivo permeation. Improved pharmacokinetic parameters like AUC, AUMC, MRT, Vd was observed for experimental nanolipo gel Vs. marketed formulation. The experimental nanolipo gel could be explored further for futuristic clinical application.

Comparative evaluation of the clinical and radiographic efficacy of 0.05% zoledronate gel as local drug delivery system in treating intrabony defects in stage III grade B periodontitis patients with and without type-2 diabetes mellitus-A randomized split-mouth clinical trial.

BACKGROUND: This 6-month randomized split-mouth and placebo-controlled clinical trial aimed to evaluate the clinical and radiographic efficacy of adjunctive use of 0.05% zoledronate (ZLN) gel as local drug delivery to scaling and root planing (SRP) in stage III, grade B periodontitis patients with and without controlled type-2 diabetes mellitus (DM). METHODS: A total of 120 infrabony sites were divided into two groups: Group-1 (non-diabetic periodontitis) and Group-2 (periodontitis + DM). A total of 60 sites in each group were randomized to receive treatment with SRP + placebo gel (control) or SRP + 0.05% ZLN gel (test). Plaque index (PI), modified sulcus bleeding index (mSBI), pocket probing depth (PPD), and relative attachment levels (RAL) were assessed at baseline, 3 and 6 months, and digital intraoral periapical and cone-beam computed tomography imaging were used to measure the linear and percentage reduction of intrabony defect depth (DD, DDR%) after 6 months. RESULTS: Group-1 showed significant reduction in PI (0.56 ± 0.15 and 0.52 ± 0.19 from 0.67 ± 0.17), mSBI (0.7 ± 0.60 and 0.47 ± 0.57 from 0.9 ± 0.48), PPD (4.6 ± 0.85 and 3.43 ± 0.63 from 6.5 ± 1.04) and gain in RAL (7.03 ± 0.85 and 5.93 ± 0.69 from 8.9 ± 1.09) in the ZLN-treated sites than the placebo sites and also from Group-2 sites after 3 and 6 months, respectively. A significant reduction in DD of 28.79% in Group-1 and 22.20% in Group-2 at ZLN sites was seen compared to placebo sites of both groups. CONCLUSION: ZLN gel applied subgingivally in infrabony pockets resulted in significant clinical improvements evident by probing depth reduction and gain in attachment levels along with radiographic evidence of more bone fill seen in non-diabetic patients compared to diabetic periodontitis patients.

A cross-sectional study on adherence to treatment and life-style modifications in hypertensive patients attending the urban health centre of a teaching hospital in Hyderabad.

Introduction: The burden of hypertension is expected to double by 2025 and adherence to treatment has a key role in disease outcome. The World Health Organization defines adherence as the extent to which a person's behaviour of taking medication, following a diet and/or exceeding life-style changes, corresponds with the agreed recommendations of health care providers. The study tries to assess the level of adherence to medication and life-style modifications in hypertensive patients. Materials and Methods: It is a cross-sectional study among patients attending urban health centres of a teaching hospital. The study population included all hypertensive patients above 30 years. Based on the prevalence of non-adherence to hypertensive medication, 70% of the sample size is calculated as 182. A Morisky medication adherence scale is used to find adherence to treatment. Life-style modification was also assessed. Scoring was done based on their adherence to treatment and life-style modifications and quantified. Results: The mean age of the study population was 55 years (38-80 years). In total, 58.33% were illiterate and 21% were retired from work. Around 87.5% had to spend money on medication. Mean weight, height, hip and waist circumference was 66 kg, 157 cm, 108 cm and 100 cm, respectively. Mean BMI was 26.6. Prevalence of good adherence to medication was 129 (70.83%) and that of good life-style modifications was 127 (70.17%). Conclusion: The adherence to medication and life-style modification was satisfactory. Family physicians have a key role in Non communicable diseases (NCD) management and should focus on ongoing education programmes for treatment adherence and life-style modifications at a community level, and grass-root level workers should conduct regular follow-up activities.

Anther Culture Efficiency in Quality Hybrid Rice: A Comparison between Hybrid Rice and Its Ratooned Plants.

An immense increase in human population along with diminished lands necessitates the increase of rice production since, it serves the human population as a staple food. Though rice hybrids (RH) are showing considerable yield enhancement over inbreds in terms of both quality and quantity, farmers' adoption of hybrid rice technology has been much slower than expected because of several constraints such as seed cost and quality. Doubled haploid (DH) technology was considered useful for the development of inbred lines from rice hybrids in a single generation. Androgenesis shows its significance in development of DHs in rice which requires an efficient method to establish the production of large population. To start the anther culture, anthers are the main component of androgenesis to be isolated from unopened spikes. However, the duration of spikes availability for anther culture coupled with the segregation of rice hybrids in the next generation requires the main crop be ratooned to reduce the cost of cultivation. Therefore, the efficiency of the androgenic method was tested in main crop using a quality indica rice hybrid, 27P63 and its ratooned ones. The effects of various factors such as cold temperature pre-treatment of boots, treatment duration, and different combination of plant growth regulators (PGR) on callus response along with shoot regeneration were tested for development of DHs from both ratooned and non-ratooned plants. The N6 medium supplemented with 2.0 mg/L 2,4-D (2,4-dichlrophenoxy acetic acid), 0.5 mg/L BAP (6-benzylamino purine), and 30 g/L maltose was found to be most effective for callusing as compared to MS (Murashige and Skoog) medium. The N6 media inducted calli showed maximum response rate for green shoot regeneration in MS media supplemented with 0.5 mg/L NAA (1-napthaleneacetic acid), 0.5 mg/L Kn (Kinetin; 6-furfurylaminopurine), 1.5 mg/L BAP and 30 g/L sucrose after 2 weeks of culture. The pre-treatment of spikes at 10 °C for 2 d followed by a 7th and 8th d were found to be most effective for callusing as well as for regeneration, producing a total of 343 green plants from ratooned and main rice hybrid, 27P63. Morpho-agronomic trait-based assessment of ploidy status revealed 94.46% diploids, 3.49% polyploids, 0.58% mixploids, and 1.45% haploids. Microsatellite markers could authenticate all 324 fertile diploids as true DHs. Though this study shows a reduction in generation of DHs from ratooned plants as compared to the main crop, manipulation of chemical factors could optimize the method to enhance the production of considerable number of DHs. Utilization of ratooned of hybrid rice in androgenesis would save time and cost of cultivation.

Temperature-dependent mucosal permeation kinetics of stigmasterol microspheres: In vivo mice model antioral candidiasis study.

Evaluation of mucosal permeation of stigmasterol from the glutaraldehyde cross linked chitosan microspheres at increasing experimental temperatures was performed. The activation energy of permeation, partition, and diffusion were estimated to understand the permeation kinetic with respect to the temperature. The formulation depicting least activation energy possessed the increased permeation thresholds of drug at the site of application. The encapsulation efficacy and mucoadhesive strength were found to be directly proportional to the polymer-emulsifier ratio. Decreased intensity in crystallography directed the molecular dispersion of microencapsulated drug. The depleted enthalpic phase transition in thermogram affirmed the stigmasterol encapsulation. The sphericity and the size of microspheres were determined by scanning electron photo micrograph. The in vivo quantification of oral Candida infection with different statistical approach and histopathological observation of infected tongue of mice on treatment with the stigmasterol encapsulated microspheres showed significant anti oral candidiasis activity by reduction of fungal colony count and recovery of papillae, reorganization of basal cell layer and newly formed papillae during 21-28 days of treatment.

Prospective 1-year follow-up study of all cured, new sputum smear positive tuberculosis patients under the Revised National Tuberculosis Control Program in Hyderabad, Telangana State, India.

BACKGROUND: Tuberculosis (TB) is one of the leading causes of mortality in India. The Revised National Tuberculosis Control Program (RNTCP) is a robust public health system to deal with TB in India. Unless the treated patient comes back to the system with signs and symptoms of TB due to relapse or re-infection, there is no mechanism of follow-up or any method to know the relapse rate in the population. We attempted to follow the patients declared as "Cured" as per the RNTCP guidelines for 1-2 years to identify the health status of the index cases and their household contacts in posttreatment phase. MATERIALS AND METHODS: In this prospective cohort study, 187 index cases, who were declared "Cured" in six randomly selected TB units of Hyderabad district, were followed up for 1-2 years through home visits by trained staff with structured data collection forms. Data were analyzed using SPSS v20.0. RESULTS: The mean age of the index cases was 33.64 (±16.10) years, and there were 75 females and 112 males. The study sample was homogenous for gender, age, smear grade, religion, marital status, smoking status, alcohol consumption, and human immunodeficiency virus status, etc., At 1-year posttreatment follow-up of 187 index cases, 143 (76.47%) were healthy and working without any symptoms of TB. Symptoms of TB were present in 26 (13.90%) cases, and seven index cases (4.06%) were re-diagnosed with TB. The 2-year posttreatment survival was 92%. CONCLUSION: Long-term follow-up of cured, new smear-positive TB cases reinforce the effectiveness of anti-TB treatment under the RNTCP as assessed by improved health outcomes in more than two-thirds of cases and posttreatment survival of 92% of index cases. We recommend continuing such follow-up for all TB cases treated under the RNTCP for effective end-TB strategy.

Analysis of tuberculosis case report in Hyderabad district of Telangana state.

BACKGROUND: The estimated incidence of TB in India was approximately 28,00,000 as per the Global TB report 2017. This accounts for a quarter of the world's TB (Tb) cases. National strategic plan, is a programme which aims at the elimination of Tb by 2018. The programme is crafted in line with other health sector strategies and global efforts, such as the draft National Health Policy 2015, World Health Organization's (WHO) End TB Strategy and the Sustainable Development Goals (SDGs) of the United Nations (UN). Key strategies under National Strategic plan: Private sector engagement, active case finding, drug resistant Tb case management, addressing social determinants including nutrition, robust surveillance system, community engagement and multisectoral approach. METHODS: In March 2018, India Tb report was released by RNTCP. An analysis of the report is done in the research article, an attempt to take forward end Tb strategy. RESULT: According to The India Tb report, 85% of new TB cases were detected, nationwide, where as 90% of new cases were detected in Hyderabad, during the same time period. Tuberculosis (Tb) notification rate (per 100 000 population), in India is 138, where as in Hyderabad district of Telengana it is 100. Both Public and private sector Tb case notification rate, of Hyderabad district was less than that of India (90,10). 6% of Tb cases were paediatric cases both Hyderabad and Nationwide. HIV status was known in 66% cases, in India and 67% in Hyderabad district of Telengana.

Formulation and evaluation of novel stomach specific floating microspheres bearing famotidine for treatment of gastric ulcer and their radiographic study

Objective: To develop and characterize multiple-unit-type oral floating microsphere of famotidine to prolong gastric residence time and to target stomach ulcer. Methods: The floating microspheres were prepared by modified solvent evaporation method. Eudragit S-100 was used as polymer. Microspheres were characterized for the micromeritic properties, floating behavior, entrapment efficiency and scanning electron microscopy. The in-vitro release studies and floating behavior were studied in simulated gastric fluid at pH 1.2. Different drug release kinetics models were also applied for all the batches. Selected formulations were also subjected for X-ray radiographic study. Results: Floating microspheres were successfully prepared by modified solvent evaporation technique. Microspheres showed passable flow properties. The maximum yield of microspheres was up to (95.11±0.35)%. On the basis of optical microscopy particle size range was found to be ranging from (52.18±182.00) to (91.64±5.16) μm. Scanning electron microscopy showed their spherical size, perforated smooth surface and a cavity inside microspheres. Microspheres were capable to float up to 20 h in simulated gastric fluid. X-ray radiographic studies also proved its better retention in the stomach. Conclusions:On the basis of the results, such dosage forms may be a good candidate for stomach targeting and may be dispensed in hard gelatin capsules.

Periodontal muco-adhesive formulations for the treatment of infectious periodontal diseases.

Extensive efforts have recently been focused on targeting a drug or delivery system in a particular region of the body for extended period of time, not only for local targeting of drugs but also for the better control of systemic drug delivery. The concept of periodontal drug delivery systems has fascinated many investigators to the possible use of various polymers, which can overcome various physiological barriers in long-term drug delivery, there by rendering the treatment more effective and safe for local disorders and systemic problems. Presence of a smooth and relatively immobile surface for placement of a bio-adhesive dosage form has made periodontal route more suitable for sustained delivery of therapeutic agents using bio-adhesive systems. Antibiotics, antiseptics and other poorly absorbable drugs can be successfully delivered via periodontium for the treatment of infectious periodontal diseases. The dosage forms include microparticles, microspheres, adhesive gels, adhesive films, adhesive creams and ointments. Bio-adhesive periodontal drug delivery system can also exert positive influence on drug effectiveness by keeping the drug in the region proximal to its absorption window and allow the targeting and localization of the drug at the specific site.

The effect of pH and organic ester penetration enhancers on skin permeation kinetics of terbutaline sulfate from pseudolatex-type transdermal delivery systems through mouse and human cadaver skins.

The purpose of this research was to prepare a pseudolatex transdermal delivery system for terbutaline sulfate and to evaluate the effect of pH and organic ester penetration enhancers on permeation kinetics of terbutaline sulfate through mice abdominal skin and human cadaver skin. An increase in the permeation flux by increasing pH was observed. The distribution coefficient of terbutaline sulfate between 1-octanol and buffers of different pH values was also pH-dependent. Furthermore, the change of the permeability coefficient with pH correlated well with the distribution coefficient by a 2-degree polynomial equation. The permeation profile and related kinetic parameters of terbutaline sulfate was determined in presence of 3 ester-type permeation enhancers incorporated in the films, viz methyl laureate, isopropyl lanolate, and isopropyl myristate. Among the 3, the more pronounced enhancing effect was obtained with isopropyl myristate, regarding the permeation flux, permeability coefficient, and diffusion coefficient. This was attributed to solubility parameter of isopropyl myristate being closer to the solubility parameter of human skin, and such a pronounced enhancing effect was probably caused by its passage across the skin barrier through the lipid pathway.

Design and characterization of mucoadhesive buccal patches of salbutamol sulphate.

Mucoadhesive patches for delivery of salbutamol sulphate were prepared using polyvinyl alcohol, hydroxypropylmethyl cellulose and chitosan. Mechanical property, swelling and bioadhesive characteristics were detemined for both plain and medicated patches. Mechanical properties were determined in presence of carbopol and polyvinylpyrrolidone. The results showed an increase in swelling after addition of salbutamol sulphate to the plain formulation. This was attributed that the salbutamol sulphate modifies the way water is bound to or taken by the polymer. A decrease in residual time was observed for polyvinyl alcohol and citosan containing formula. High drug release was obtained from polyvinyl alcohol compared to the hydroxypropylmethylcellulose. Physical characteristics of the studied patches showed promising with good bioadhesion.