PLANT BASED BIOAVAILABILITY ENHANCERS

Many of the synthetic as well as herbal drugs despite of their notable in vitro finding demonstrate insignificant in vivo activity majority of times due to poor bioavailability. As per Biopharmaceutical Classification System (BCS) one of the main concern is low solubility and/or permeation of drugs resulting in reduced absorption and poor bioavailability. To overcome these issues the various strategies have been adopted including use of permeation enhancers which are also known as bioenhancers. Bioenhancers are synthetic or natural compounds that increases the bioavailability of drugs and nutrients such as vitamins, amino acids, minerals, etc. into the systemic circulation and at the site of action for exhibiting improved therapeutic action. By improving bioavailability, bioenhancers can lead to reduction in drug dose, decrease in the treatment period and can circumvent the problem of drug resistance. Numerous studies have reported application of synthetic bioenhancers. On the other hand, owing to the natural origin, plant based bioenhancer can serve as better alternative. Literature review have revealed that the plant-based bioenhancers have been used in with a wide varieties of drugs including antibiotics, antiviral and anti-cancer. These can be categorized based on their sources and the mechanism of activity. This review will provide a systematic and detailed overview of the various plant based bioenhancers and applications.

Clinical and Immunological Factors Associated with Recommended Trough Levels of Adalimumab and Infliximab in Patients with Crohn’s Disease

Introduction: Up to 40% of patients with Crohn’s disease do not respond to treatment with anti-TNF or lose response after the initial benefit. Low drug concentrations have been proposed as the main predictor of treatment failure. Our aim was to study the immunological profile and clinical evolution of patients with Crohn’s disease according to the anti-TNF dose and serum trough levels.Methods: Crohn’s disease patients in remission treated with infliximab or adalimumab at stable doses for at least for 3 months were included. Serum levels of anti-TNF, TNF-α, interferon-γ, and interleukin IL-12, IL-10, and IL-26 were determined in blood samples taken just before drug administration. Patients were classified according to anti-TNF levels below, within, or above the target level range and the use of intensified doses. Clinical evolution at 6 months was analyzed.Results: A total of 62 patients treated with infliximab (8 on intensified schedule) and 49 treated with adalimumab (7 on intensified schedule) were included. All infliximab-treated patients showed levels within the recommended range, but half of adalimumab-treated patients were below the recommended range. A significant negative relationship between body weight and adalimumab levels was observed, especially in patients treated with intensified doses. Patients with infliximab levels over 8 µg/ml presented higher median IL-10 than patients with in-range levels (84.0 pg/ml, interquartile range [IQR] 77.0–84.8 vs. 26.2 pg/mL, IQR 22.6–38.0; p < 0.001), along with lower values of interferon-γ (312.9 pg/ml, IQR 282.7–350.4 vs. 405.6 pg/ml, IQR 352.2–526.6; p = 0.005). Patients receiving intensified versus non-intensified doses of infliximab showed significantly higher IL-26 levels (91.8 pg/ml, IQR 75.6–109.5 vs. 20.5 pg/ml, IQR 16.2–32.2; p = 0.012), irrespective of serum drug levels. Patients with in-range levels of adalimumab showed higher values of IL-10 than patients with below-range levels (43.3 pg/ml, IQR 35.3–54.0 vs. 26.3 pg/ml, IQR 21.6–33.2; p = 0.001). Patients treated with intensified vs regular doses of adalimumab had increased levels of IL-12 (612.3 pg/ml, IQR 570.2–1353.7 vs. 516.4 pg/mL, IQR 474.5–591.2; p = 0.023). Four patients with low adalimumab levels (19%) and four treated with intensified doses were admitted to a hospital during a follow-up compared to none of the patients with levels within the range.Conclusion: Patients with Crohn’s disease treated with infliximab and adalimumab exhibit differences in serum levels of cytokines depending on the drug, dose intensification, and steady state trough serum levels.

Reconciling Oxygen and Aerosol Delivery with a Hood on In Vitro Infant and Paediatric Models

This study aimed to evaluate optimal aerosol and oxygen delivery with a hood on an infant model and a paediatric model. A facemask and a hood with three inlets, with or without a front cover, were used. A small-volume nebuliser with a unit-dose of salbutamol was used for drug delivery and an air entrainment nebuliser was used to deliver oxygen at 35%. Infant and paediatric breathing patterns were mimicked; a bacterial filter was connected to the end of a manikin trachea for aerosol drug collection, and an oxygen analyser was used to measure the oxygen concentration. For the infant model, inhaled drug dose was significantly higher when the nebuliser was placed in the back of the hood and with a front cover. This was verified by complementary computational simulations in a comparable infant-hood model. For the paediatric model, the inhaled dose was greater with a facemask than with a hood. Oxygen delivery with a facemask and a hood with a front cover achieved a set concentration in both models, yet a hood without a front cover delivered oxygen at far lower concentrations than the set concentration.

Animal Model for Glucocorticoid Induced Osteoporosis: A Systematic Review from 2011 to 2021

Clinical and experimental data have shown that prolonged exposure to GCs leads to bone loss and increases fracture risk. Special attention has been given to existing emerging drugs that can prevent and treat glucocorticoid-induced osteoporosis GIOP. However, there is no consensus about the most relevant animal model treatments on GIOP. In this systematic review, we aimed to examine animal models of GIOP centering on study design, drug dose, timing and size of the experimental groups, allocation concealment, and outcome measures. The present review was written according to the PRISMA 2020 statement. Literature searches were performed in the PubMed electronic database via Mesh with the publication date set between April, 2011, and February 2021. A total of 284 full-text articles were screened and 53 were analyzed. The most common animal species used to model GIOP were rats (66%) and mice (32%). In mice studies, males (58%) were preferred and genetically modified animals accounted for 28%. Our work calls for a standardization of the establishment of the GIOP animal model with better precision for model selection. A described reporting design, conduction, and selection of outcome measures are recommended.

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects.

COVID-19 Pandemic Impact on Severe Alopecia Areata Patients

<b><i>Introduction:</i></b> The pandemic of COVID-19 has several implications for patients with chronic stress-sensitive diseases such as alopecia areata (AA). On the other hand, the vulnerability of AA patients using immunosuppressives to a more severe infection is in the shadow of ambiguity. This teledermatology study aimed to evaluate the course and outcome of AA in patients during this challenging period. <b><i>Methods:</i></b> Patients with AA who had previously received systemic therapy included in this study. Information about demographic data, AA history, characteristics, and treatments, hair loss progression, Corona Disease Anxiety Scale (CDAS), adherence to protective measures against the COVID-19, possible infection, and its features obtained via a telephone call. <b><i>Results:</i></b> A total of 57 patients participated. The majority (84.2%) of the participants had mild anxiety assessed by CDAS. Two patients (3.5%) had got infected with COVID-19. Twenty-one (36.8%) participants experienced hair loss progression. Hair loss progression correlated with drug dose reduction (OR: 46.09, 95% CI 5.48–387.14, <i>p</i> &#x3c; 0.001) although it did not influence by the level of anxiety evaluated by the CDAS (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> The anxiety perceived by severe AA patients about COVID-19 is mild; however, many experience hair loss progressions owing to their drug dose reduction.

Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery

Pulmonary hypertension (PH) is a progressive disease that eventually leads to heart failure and potentially death for some patients. There are many unique advantages to treating pulmonary diseases directly and non-invasively by inhalation aerosols and dry powder inhalers (DPIs) possess additional unique advantages. There continues to be significant unmet medical needs in the effective treatment of PH that target the underlying mechanisms. To date, there is no FDA-approved DPI indicated for the treatment of PH. Fasudil is a novel RhoA/Rho kinase (ROCK) inhibitor that has shown great potential in effectively treating pulmonary hypertension. This systematic study is the first to report on the design and development of DPI formulations comprised of respirable nanoparticles/microparticles using particle engineering design by advanced spray drying. In addition, comprehensive physicochemical characterization, in vitro aerosol aerosol dispersion performance with different types of human DPI devices, in vitro cell-drug dose response cell viability of different human respiratory cells from distinct lung regions, and in vitro transepithelial electrical resistance (TEER) as air-interface culture (AIC) demonstrated that these innovative DPI fasudil formulations are safe on human lung cells and have high aerosol dispersion performance properties.

Effects of Recovery-Orientation on the Use of Forced Medication and Maximum Daily Drug Dose: The “Weddinger Modell”

Objective: The aim of the present study was to analyze the effects of the implementation of the Recovery-orientated psychiatric care concept “Weddinger Modell” on the incidence of forced medication, the total number of forced medication incidents per affected case, the maximum dose of a singular forced medication and the maximum voluntary daily drug dose of different psychotropic drugs administered during an inpatient stay.Methods: This retrospective case-control study included 234 patients. A pre/post-comparison of patients on two acute psychiatric wards before (control group, n = 112) and after (intervention group, n = 122) the implementation of the Weddinger Modell in 2010 was performed. Patient data was selected at two reporting periods before and at two reporting periods after 2010.Results: No significant differences were found in the incidence of forced medication and the total number of forced medications. A significant reduction of the maximum forced medication dose of haloperidol in the intervention group was seen. Furthermore, the analysis of the intervention group showed a significant reduction of the maximum voluntary daily drug doses of clozapine, haloperidol and risperidone.Discussion: The results indicate that the implementation of the Weddinger Modell had no effect on the incidence of forced medication, but it can help to improve the approach to psychotropic drugs. Despite the reduction of mechanical coercive measures by the model, as shown in a previous study, there is no increase in forced medications or administered drug doses. Focus on Recovery helps in reducing coercion in acute psychiatric care.

Anesthesia Management in Intramural Uterine Myoma and Obesity Morbid Patients Who Underwent Myomectomy Perlaparatomy

Introduction. Obesity is a condition that increases the challenges in the surgical process. Obesity increases the risk of sleep apnea and affects anaesthetics. This case report aims to discuss the management of anaesthesia in a patient with morbid obesity. Case. Female, 26 years old, with intramural uterine myoma and morbid obesity, will undergo myomectomy per laparotomy with ASA II physical status, performed anaesthesia with general anaesthesia intubation technique using the anaesthetic agent Propofol 1-2.5 mg/kg titration until the patient falls asleep, fentanyl 1-2 mcg/kg, then the patient was intubated in a ramped position with sleep non-apnea. After it was confirmed that the ETT was entered, 30 mg of a muscle relaxant (atracurium) was added. The operation lasts 1 hour 30 minutes, with a bleeding 250 cc, hemodynamically stable. Conclusion. Morbid obesity has extraordinary implications for anaesthetic management. Various considerations for patients with morbid obesity are needed starting from the preoperative, intraoperative, to postoperative periods. Regional anaesthesia is preferred because the physiological function of unhealthy obese patients is impaired due to excess body weight. Selection of anaesthetic agent and calculation of drug dose is crucial to know because there is a change in the volume of distribution. The pharmacokinetics of most general anaesthetics are affected by the adipose tissue mass, produce a prolonged drug effect, and less predictable.