Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen

The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting

Alginatne mikrosfere naproksen natrija obložene Eudragitom S-100: Priprava, optimizacija i in vitro vrednovanje

The aim of the study was to prepare site specific drug delivery of naproxen sodium using sodium alginate and Eudragit S-100 as a mucoadhesive and pH-sensitive polymer, respectively. Core microspheres of alginate were prepared by a modified emulsification method followed by cross-linking with CaCl2, which was further coated with the pH dependent polymer Eudragit S-100 (2.5 or 5 %) to prevent drug release in the upper gastrointestinal environment. Microspheres were characterized by FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and evaluated by scanning electron microscopy, particle size analysis, drug loading efficiency, in vitro mucoadhesive time study and in vitro drug release study in different simulated gastric fluids. Stability studies of the optimized formulation were carried out for 6 months. SEM images revealed that the surface morphology was rough and smooth for core and coated microspheres, respectively. Core microspheres showed better mucoadhesion compared to coated microspheres when applied to the mucosal surface of freshly excised goat colon. The optimized batch of core microspheres and coated microspheres exhibited 98.42 ± 0.96 and 95.58 ± 0.74 % drug release, respectively. Drug release from all sodium alginate microsphere formulations followed Higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the Korsmeyer-Peppas equation with a Fickian kinetics mechanism. Stability study suggested that the degradation rate constant of the microspheres was minimal, indicating 2 years shelf life of the formulation.Cilj istraživanja bila je ciljana isporuka naproksen natrija koristeći natrijev alginat i Eudragit S-100 kao mukoadhezivne, odnosno pH-osjetljive polimere. Jezgra mikrosfera od alginata pripravljena je modificiranom metodom emulgiranja te umrežavanjem pomoću otopine CaCl2. Sljedeći korak u pripravi mikrosfera bilo je oblaganje s pH osjetljivim polimerom Eudragit S-100 (2,5 ili 5 %) čime je spriječeno oslobađanje lijeka u gornjem dijelu gastrointestinalnog trakta. Mikrosfere su okarakterizirane FT-IR spektroskopijom, difrakcijom rendgenskih zraka, diferencijalnom pretražnom kalorimetrijom i pretražnom elektronskom mikroskopijom. Nadalje, analizirana je veličina čestica, količina uklopljenog lijeka, mukoadhezivna svojstva in vitro te oslobađanje lijeka in vitro u različitim simuliranim gastričnim fluidima. Testovi stabilnosti optimiziranih pripravaka praćeni su tijekom 6 mjeseci prema smjernicama ICH. SEM snimke otkrile su da je površina jezgre mikročestica neravna, dok je površina obloženih mikrosfera glatka. Jezgre mikrosfera imale su jače izražena mukoadhezivna svojstva nego obložene mikrosfere na testovima provedenim na svježe izrezanim dijelovima debelog crijeva koze. Iz optimiziranih neobloženih i obloženih mikrosfera oslobađa se 98.42 ± 0.96, odnosno 95.58 ± 0.74 % lijeka. Oslobađanje lijeka iz svih formulacija slijedilo je kinetiku po Higuchiju. Oslobađanje iz obloženih mikrosfera slijedilo je Korsmeyer-Peppasovu jednadžbu i kinetiku po Ficku. Studije stabilnosti pokazale su minimalnu razgradnju, te prihvatljivu stabilnost tijekom dvogodišnjeg skladištenja

SARS-CoV-2: comparison of IgG levels at 9 months post second dose of vaccination in COVID-survivor and COVID-naïve healthcare workers

Background: Natural (asymptomatic/symptomatic COVID-19 infection) and artificial (vaccination) exposure to the pathogen represent two modes of acquiring active immunity. No definitive guidelines exist regarding whether COVID-survivors (with infection/re-infection/re-re-infection in the three COVID-19 waves) require a modified vaccination schedule. Most countries are offering a third vaccine dose and many are contemplating a fourth dose. Our aim was to gauge the IgG-antibody levels 9m post second vaccination in healthcare workers (HCW) and compare these with IgG-levels 1m post-vaccination in the same cohort for any decline, and to compare the post-vaccination IgG-levels in COVID-survivors and COVID-naïve HCW at 9m.Methods: This prospective observational single-centric cohort study included 63 HCW of either sex, aged 18-70y who completed 9m post-vaccination. The IgG-titre was tested at 9-10m post second vaccination in COVID-survivors and COVID-naïve HCW.Results: At 1m and 9m post-vaccination IgG-levels in COVID-survivors (23.097±4.58 and 15.103±4.367 respectively; p<0.0001) and COVID-naïve HCW (16.277±6.36 and 9.793±6.928 respectively; p=0.0013) had unequal variance (Welsch test; p=0.0022 at 9m). 9/31 COVID-naïve HCW but none of the 32 COVID-survivors tested COVID-positive in the second wave post second vaccination. 11/31 and 3/32 HCW belonging to the former and latter groups developed COVID-19 in the third wave consequently deferring their third/precautionary vaccination.Conclusions: Although HCW with IgG-levels in all brackets developed COVID-19, the severity of symptoms corresponded with the IgG-levels. COVID-19 is here to stay, but in peaceful co-existence in endemic proportions. Considering evidence that immunity acquired by vaccination/natural infection is ephemeral, re-invention of vaccines to match the ever-mutating virus is foreseen.

Low-dose prophylaxis protocol for heterotopic ossification after hip preservation surgery in a sport participants cohort

Background: Heterotopic ossification (HO) is a well-known complication of arthroscopic and open surgical treatment of femoroacetabular impingement (FAI). Incidence of heterotopic ossification has been reported in the literature between 0% and 44% after hip arthroscopy and between 18.2% and 25% after anterior mini-open surgery. Currently, pharmacological prophylaxis with NSAIDs and selective COX-2 inhibitors are commonly used and their effectiveness is well documented in literature. Hypothesis: We hypothesized that the low-dose prophylaxis protocol with selective cox-2 inhibitors decreases the risk of heterotopic ossification in open or arthroscopic hip preservation surgery in athletes. Methods: This study is an analysis of prospectively gathered data on 98 sport participant patients who underwent arthroscopic or anterior mini-open treatment for FAI between April 2008 and April 2018. All the patients received postoperative oral prophylaxis with 60 mg etoricoxib once daily for two weeks. Post-operative X-rays were performed at 1, 3, and 12 months after surgery and reviewed by two orthopedic surgeons blinded to the type and side of surgery. HO were graded according to the Brooker classification. Descriptive statistics was used to analyze demographic data. Bivariate analysis was performed to analyze the association of HO with each of the following variables: type of surgery, physical activity, time of evolution of symptoms, age at surgery, and sex. Finally, a regression model analysis was performed to determine the presence of confounding effects between variables. Results: The study cohort was composed of 54 patients in the arthroscopic treatment group and 44 patients in the anterior mini-open group. HO was identified in 6 (13.6%) patients in the mini-open group. No HO was identified in the arthroscopic group. In the bivariate analysis, “type of surgery” was the only variable that showed a statistically significant association with HO (p = 0.007). Conclusion: Results of this study suggest that anterior mini-open treatment was characterized by a higher risk of HO development compared to hip arthroscopy for femoroacetabular impingement treatment regardless of pharmacological prophylaxis. The treatment regimen of 60 mg etoricoxib daily for two weeks was an effective prophylaxis for HO formation in sport participant patients compared with data available in the literature

Heat shock protein 70 as a biomarker of heat stress in a simulated hot cockpit

Background: Fighter pilots are frequently exposed to high temperatures during high-speed low-level flight. Heat strain can result in temporary impairment of cognitive functions and when severe, loss of consciousness and consequent loss of life and equipment. Induction of stress proteins is a highly conserved stress response mechanism from bacteria to humans. induced stress protein levels are known to be cytoprotective and have been correlated with stress tolerance. Although many studies on the heat shock response mechanisms have been performed in cell culture and animal model systems, there is very limited information on stress protein induction in human subjects. Hypothesis: Heat shock proteins (Hsp), especially Hsp70, may be induced in human subjects exposed to high temperatures in a hot cockpit designed to simulate heat stress experienced in low flying sorties. Methods: Six healthy volunteers were subjected to heat stress at 55degreesC in a high temperature cockpit simulator for a period of 1 h at 30% humidity. Physiological parameters such as oral and skin temperatures, heart rate, and sweat rate were monitored regularly during this time. The level of Hsp70 in leukocytes was examined before and after the heat exposure in each subject. Conclusions: Hsp70 was found to be significantly induced in all the six subjects exposed to heat stress. The level of induced Hsp70 appears to correlate with other strain indicators such as accumulative circulatory strain and Craig's modified index. The usefulness of Hsp70 as a molecular marker of heat stress in humans is discussed

Heat shock protein 70 as a biomarker of heat stress in a simulated hot cockpit

Background: Fighter pilots are frequently exposed to high temperatures during high-speed low-level flight. Heat strain can result in temporary impairment of cognitive functions and when severe, loss of consciousness and consequent loss of life and equipment. Induction of stress proteins is a highly conserved stress response mechanism from bacteria to humans. Induced stress protein levels are known to be cytoprotective and have been correlated with stress tolerance. Although many studies on the heat shock response mechanisms have been performed in cell culture and animal model systems, there is very limited information on stress protein induction in human subjects. Hypothesis: Heat shock proteins (Hsp), especially Hsp70, may be induced in human subjects exposed to high temperatures in a hot cockpit designed to simulate heat stress experienced in low flying sorties. Methods: Six healthy volunteers were subjected to heat stress at 55°C in a high temperature cockpit simulator for a period of 1 h at 30% humidity. Physiological parameters such as oral and skin temperatures, heart rate, and sweat rate were monitored regularly during this time. The level of Hsp70 in leukocytes was examined before and after the heat exposure in each subject. Conclusions: Hsp70 was found to be significantly induced in all the six subjects exposed to heat stress. The level of induced Hsp70 appears to correlate with other strain indicators such as accumulative circulatory strain and Craig's modified index. The usefulness of Hsp70 as a molecular marker of heat stress in humans is discussed

Novel drug delivery approaches on antiviral and antiretroviral agents

Viruses have the property to replicate very fast in host cell. It can attack any part of host cell. Therefore, the clinical efficacy of antiviral drugs and its bioavailability is more important concern taken into account to treat viral infections. The oral and parenteral routes of drug administration have several shortcomings, however, which could lead to the search for formulating better delivery systems. Now, a day′s novel drug delivery systems (NDDS) proved to be a better approach to enhance the effectiveness of the antivirals and improve the patient compliance and decrease the adverse effect. The NDDS have reduced the dosing frequency and shorten the duration of treatment, thus, which could lead the treatment more cost-effective. The development of NDDS for antiviral and antiretroviral therapy aims to deliver the drug devoid of toxicity, with high compatibility and biodegradability, targeting the drug to specific sites for viral infection and in some instances it also avoid the first pass metabolism effect. This article aims to discuss the usefulness of novel delivery approaches of antiviral agents such as niosomes, microspheres, microemulsions, nanoparticles that are used in the treatment of various Herpes viruses and in human immunodeficiency virus (HIV) infections

Neuroretinitis as presenting and the only presentation of Lyme disease: Diagnosis and management

We present a case of neuroretinitis as presenting and the only presentation of Lyme disease in a 25-year-old female who visited hilly areas in the Himalayas of North India. She presented with right eye sudden and painless blurring of vision. Her vision at presentation was 20/60. She had fundus examination; fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) imaging showed classical features of neuroretinitis. No other organ was involved. Oral steroids were prescribed and relevant investigations sent for noninfective and infective causes. Worsened visual acuity (VA) to hand movement and positive IgM titers for Borrelia burgdorferi led to the diagnosis of Lyme disease-associated neuroretinitis. Treatment with oral doxycycline plus oral steroids for 4 weeks revealed VA of 20/20 and resolution of fundus and OCT changes. Neuroretinitis as presenting and the only presentation of Lyme disease will be discussed with serial fundus, FFA, and OCT pictures

Ventriculoperitoneal Shunt-Associated Meningitis Caused by Candida auris: A Case Report

Candida auris was first isolated in Japan in 2008. Since then, it has become an emerging global threat due to its role in outbreaks in healthcare facilities and its decreased susceptibility to multiple antifungal agents. We report a case of ventriculoperitoneal shunt-associated meningitis caused by C. auris in a patient who had a history of tubercular meningitis and hydrocephalus. The isolate was initially misidentified as Candida krusei based on purple-colored colonies on Modified HiCrome Candida Differential Agar but was finally identified as C. auris on VITEK-2 compact (version 8.01). The isolate had a high minimum inhibitory concentration (MIC) for fluconazole, whereas the MICs for other major classes of antifungals were low