Dosing Frequency Research Articles

Hierarchical adhesive hydrogel microparticles with galantamine hydrobromide encapsulation for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia in aged individuals. Galantamine hydrobromide (GAH) is an approved medication for AD that has been shown to significantly enhance cognitive function, effectively manage behavioral symptoms, and improve performance in essential daily activities. However, the side effects of these drugs include nausea and vomiting, significant fluctuations in blood concentration, and poor patient compliance. Therefore, improving the route of administration and enhancing therapeutic efficacy are major research focuses. Here, we propose the use of hierarchically structured hydrogel-encapsulated mesoporous silica nanocarriers (MSNs) to encapsulate GAH, with the goal of minimizing adverse reactions in the stomach. By enabling the slow release of the drug over an extended period, these hydrogels aim to reduce the frequency of dosing, thereby improving the efficiency of drug administration and enhancing patient compliance. Owing to these properties, drug-carrying microcapsules are capable of achieving optimal drug delivery and have emerged as excellent candidates for AD therapy. We believe that this technology has the potential to significantly impact clinical treatment.

Enhanced long-acting simvastatin delivery via effervescent powder-carrying hollow microneedles and nanocrystal-loaded microneedles

Hyperlipidemia and its associated cardiovascular complications are the major causes of mortality and disability worldwide. Simvastatin (SIM) is one of the most commonly prescribed lipid-lowering drugs for the treatment of hyperlipidemia by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. However, the extensive first-pass metabolism leading to low oral bioavailability and frequent daily doses may lead to poor patient compliance and adverse effects caused by plasma fluctuations. To overcome these challenges, this work purposed two microneedle (MN) delivery strategies for the potential enhancement of SIM delivery. Firstly, nanocrystal (NC) formulations of SIM were investigated, followed by incorporation into a trilayer dissolving microneedle (DMN) design. Furthermore, a novel effervescent powder-carrying MN (EMN) design was developed to enhance intradermal delivery by incorporating the effervescent agents into the drug powder. Both MN approaches exhibited significantly improved permeation and in-skin deposition ability in the Franz cell study, with the ex vivo delivery efficiency of 64.33 ± 6.17 % and 40.11 ± 4.53 % for EMNs and DMNs, respectively. Most importantly, in vivo studies using a female Sprague-Dawley rat model confirmed the successful delivery of SIM from NCs-loaded DMNs (Cmax = 287.39 ± 106.82 ng/mL) and EMNs (Cmax = 203.05 ± 17.07 ng/mL) and maintain therapeutically relevant plasma concentrations for 15 days following a single application. The enhanced bioavailabilities of DMNs and EMNs were 24.28 % and 103.82 %, respectively, which were both significantly higher than that of conventional oral administration.

Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial

IntroductionThe systemic inflammatory response syndrome during the perioperative period of cardiac surgery can lead to serious postoperative complications and significantly increase the hospital mortality rate. Colchicine, a widely used traditional...

Real-world experience with clinical management of talquetamab in relapsed/refractory multiple myeloma: a qualitative study of US healthcare providers

Objective Talquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management. Methods In February/March 2024, individual in-depth interviews (IDIs; n = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel (n = 6) further discussed current practices. Results The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient (n = 5), outpatient (n = 3), and hybrid models (n = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD (n = 7) and treatment phases (n = 8). Six participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. Conclusion This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.

Stated preferences for long-acting injectable ART among mobile men living with HIV in Malawi: a qualitative study

Background: Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV). Methods: We conducted a qualitative sub-study within two trials (ENGAGE and IDEaL) in 24 health facilities in Malawi that enrolled MLHIV >15 years not on ART. We conducted in-depth interviews with a stratified random sample of participants who had taken oral ART and self-reported mobility (travel) during the 6-month study (>1 trip of >3 nights). Interviews described cabotegravir/rilpivirine and asked about clients’ stated preferences for LAI vs. oral ART and their reasoning. Interviews were translated, transcribed, coded in Atlas.ti, and analyzed using framework analysis. Results: We interviewed 29 mobile MLHIV from 1 July to 30 August 2022, median age 36 (IQR:31-41), mean 28 nights away in last six months (SD: 40). Nearly all participants (26/29) expressed a preference for LAI over daily oral ART because LAI would reduce the risks of forgetting to take pills and unwanted disclosure. Three men preferred oral ART primarily due to fear of side effects from a new medication. A few men reported they would change their preference if injection site reactions prevented them from working. Conclusion: Mobile MLHIV in Malawi with previous ART adherence challenges expressed strong stated preferences for LAI over daily oral ART. Further research is needed to understand implementation challenges and potential effectiveness of LAI among harder-to-reach populations.

Does dosing frequency of anti-CD20 therapies blunt vaccine responses and increase COVID-19 susceptibility in patients with multiple sclerosis?

Does dosing frequency of anti-CD20 therapies blunt vaccine responses and increase COVID-19 susceptibility in patients with multiple sclerosis?

Pharmacokinetic model-based assessment of factor IX prophylaxis treatment regimens in severe hemophilia B

An important aspect of improving care for people with hemophilia B (HB) is developing optimal treatment strategies. Here we aimed to provide in-silico evidence, comparing the estimated optimal posology of factor IX (FIX) products to support the patient-physician decision-making process. A population pharmacokinetic (popPK) model-based assessment comparing the performance of FIX products (rFIX, rIX-FP, rFIXFc, N9-GP) was developed. PopPK analyses were used to determine a product’s optimal posology to target predefined steady-state FIX activity trough levels in a hypothetical population of 10,000 people with severe HB. Model-derived optimal posologies were compared across several parameters including trough levels, proportion of patients per regimen and consumption, considering 64 hypothetical patient scenarios of different FIX trough level targets and ages. Results indicated a marked difference between FIX products estimated to achieve target trough levels, consumption and dosing frequencies. rIX-FP was associated with higher trough levels than rFIX and rFIXFc, at a lower weekly dose and administration frequency, across all age groups. N9-GP use in adolescents and adults was associated with lower consumption compared with rIX-FP. Insights from this study may be utilized by clinicians to inform decision-making, by considering the model-generated estimated optimal posologies alongside multiple clinical factors and patient preferences.

Prevalence and associated factors of non-adherence to antihyperlipidemic medication: a nationwide cross sectional survey in Pakistan

Hyperlipidemia significantly contributes to the risk of developing cardiovascular diseases. However, about half of the patients do not adhere to their antihyperlipidemic medications, leading to healthcare costs and premature mortality. This study's objective was to determine the prevalence and associated factors of non-adherence to antihyperlipidemic medications. The study covered hypertensive patients (21,451) aged 21–75 years, presenting to the primary and secondary healthcare facilities across Pakistan (covering 21 divisions) from January 2022 to April 2023. The outcome intended was non-adherence to antihyperlipidemic medication, which was assessed by SEAMS and pill-counting methods (non-adherence < 80%). The study found overall non-adherence to antihyperlipidemic medication of 60.6% across Pakistan, with the highest non-adherence rates found in Azad Jammu and Kashmir (71.9%) and the lowest in Islamabad (47.7%). Multivariable logistic regression analysis revealed that female, no health card (Sehat Sahulat Program government insurance), < 5 years of illness, < 5 daily medications, and dose frequency of twice daily revealed a positively significant association with non-adherence. While monthly income 51,000–100,000, graduation level of education, Muhajir, and hyperlipidemia with one comorbid condition had a significant negative association with the non-adherence. Antihyperlipidemic non-adherence is a multifaceted, multifactorial, profound problem requiring a multipronged approach.

Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35mg kg-1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency.

Prescribing Errors in an Ambulatory Care Setting: Mitigating Risks in Outpatient Medication Orders, Cross-Sectional Review

ABSTRACT Introduction Prescribing errors (PEs) are the most common type of medication error, which may occur by prescribing the wrong medication, improper dose, dosage, and/or even prescribing a drug to the wrong patient. The present study aims to compile PEs that were generated in an ambulatory care setting at a tertiary-care hospital in Saudi Arabia. Methods A retrospective cross-sectional review was conducted for all reported PEs in ambulatory care clinics for 3 years. The potential hazardous outcomes of these PEs were classified according to the medication error index. Results A total of 897 records containing 1199 PEs were retrieved. More than a third of prescribers had frequently committed PEs—ranging from 2 to 39 times. The most encountered errors were prescribing incorrect doses, medication duplication, incorrect dosing frequency, and inappropriate duration (34.5%, 14.1%, 11.6%, and 9.8%, respectively). The most frequent mistakes were when prescribing antibiotics (22.9%) and drugs for cardiovascular conditions (18.5%). Most errors were of mild to moderate severity, mostly type-B near-miss errors and did not reach patients. Only two prescription events (0.17%) had severe consequences that required intervention to avoid any subsequent harm or damage. Conclusion The current investigation has revealed a substantial percentage of PEs, mostly in internal medicine and cardiology departments. Although PEs are undoubtedly not easy to avoid, monitoring and recognizing these inaccuracies is pivotal to preventing potential harm and promoting patient safety.

A Pharmacologic Evaluation of Buprenorphine in Pregnancy and the Postpartum Period.

The dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy. To compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores. Prospective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6-8 hours each) during pregnancy or postpartum. Participants were on a stable daily dose of 2-8 mg sublingual buprenorphine every 6 or 8 hours. The dosing frequency was selected by the participant. On study day, baseline measurements of plasma buprenorphine, pupil diameter, COWS, and craving scores were obtained, then the usual morning dose was taken, and measurements were repeated several times over 1 dosing interval. The dose-normalized area under the plasma buprenorphine concentration time curve was significantly (P = 0.036) lower during pregnancy (155 ± 52 ng × min/mL) than postpartum (218 ± 113 ng × min/mL). Buprenorphine trough concentrations were similar at the start (1.1 ± 0.7 ng/mL) and end of a dosing cycle (1.2 ± 0.8 ng/mL) regardless of dosing frequency. Pupillary diameter, COWS, and craving scores returned to baseline as buprenorphine concentrations approached ~1 ng/mL. Pregnant people require a higher dose of buprenorphine to achieve concentrations comparable to nonpregnant people. There is a temporal relationship between the plasma buprenorphine concentration and the pharmacodynamic markers of pupillary diameter, COWS, and craving scores. An average plasma concentration of ~1 ng/mL was associated with the lowest level of COWS and craving scores.

Patient and care partner perspectives and preferences related to myasthenia gravis treatment: A qualitative study.

Due to the high symptom and treatment burden in myasthenia gravis (MG), understanding patient and care partner perspectives and preferences is crucial. This study used voice analysis and virtual focus groups to understand patient and care partner experiences with MG-related symptoms, treatments, and preferences. The voice analysis via social media listening used artificial intelligence-powered tools to gather and structure public digital conversations on MG. Focus groups included people living with MG and care partners who completed a questionnaire and participated in a 1-h virtual session facilitated using a semi-structured interview guide. Qualitative data were aggregated, transcribed, and thematically analyzed. The voice analysis examined 11,554 posts from 8321 individuals, discussing MG symptoms, treatments, and burden. Of 7563 symptom-related posts, 5902 (78%) conveyed negative, 1427 (19%) neutral, and 234 (3%) positive sentiment. The most frequently mentioned symptoms were categorized as dysarthria, muscle weakness, and dysphagia. MG treatment sentiment analysis identified 6667 posts (67%) as neutral, 2887 (29%) as negative, and 350 (4%) as positive. For the focus groups, 15 individuals (12 patients and 3 care partners) completed the questionnaire and 14 participated in the virtual focus group sessions. The 15 participants who completed the questionnaire prioritized treatment convenience, symptom control for improved quality of life, and preventing potential MG crises in their current treatment. New treatment expectations included increased effectiveness, less frequent dosing, faster onset, and fewer side effects. Participants were also receptive to wearable medication delivery systems placed on the body and valued direct involvement in treatment decisions. Patients and care partners are often negatively impacted by MG symptoms and value convenient and fast-acting treatments that control symptoms with minimal side effects. Considering patient preferences may help optimize treatment decisions and improve patients' overall well-being and satisfaction in their care.

Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

Exploring the experience of multiple sclerosis patients in Turkey: Insights from a national survey

Objective: To evaluate sociodemographic profile, clinical characteristics, disability and treatment status of multiple sclerosis (MS) patients in Turkey with respect to patient perspectives and expectations. Methods: A total of 2,176 MS patients participated in this cross-sectional questionnaire survey including items on sociodemographic, disease and treatment characteristics, daily life and perspectives and expectations. Results: Mean (SD) patient age was 36.4(9.4) years and 76.3% of patients were females. The numbness/weakness in the extremities (57.3%) was the most common presenting symptom. Overall, 56.8% reported treatment switch (due to attacks in 47.3%), while 22.2% reported physical disability and 39.7% reported work-related problems. Males had higher rate of MS-related physical disability (33.0% vs. 19.0%, p&lt;0.001) than females. Use of an assistive device was a more common in patients with longer disease duration (≥15 years; 39.0%) and in those under IV treatment (64.0%). Nearly half of patients reported significant concerns related to uncertainty of the future and impaired quality of life as well as lack of hope for future improvement. The majority of patients reported that they would prefer less frequent SC injection dosing and 43.3% reported preference for monthly high- efficacy SC injection. Conclusion: This nationwide questionnaire-based study in Turkish MS patients revealed the altered disability status with respect to sociodemographic profile, and altered treatment expectations specific to the route of administration, in addition to significant concerns regarding the uncertainty of the future, impaired quality of life and lack of hope for future improvement in nearly half of patients.

51604 Methotrexate Test Dose Use and Frequency of Laboratory Abnormalities in Patients Initiating Treatment

51604 Methotrexate Test Dose Use and Frequency of Laboratory Abnormalities in Patients Initiating Treatment

Pharmacokinetic Evaluation of a Topical Extended-release Analgesic in Mice.

Mice often undergo painful procedures and surgeries as part of biomedical research protocols. Buprenorphine, a partial μ-opioid receptor agonist and κ receptor antagonist, is commonly used to alleviate the pain associated with such procedures. Due to its pharmacokinetic profile, buprenorphine requires frequent dosing, resulting in handling stress that can impact animal welfare and study data. A long-acting transdermal buprenorphine formulation (LA-bup) was recently approved for use in cats to provide up to 4 d of postoperative analgesia. In this study, we characterized the pharmacokinetics of a single topical dosing of LA-bup in male and female CD-1 mice administered a 0.36-mg or 18-μL topical dose at select time points. Plasma buprenorphine concentrations were evaluated at 0.25, 0.5, 1, 1.5, 2, 4, 8, 24, 48, and 72 h (n = 3 mice/time point) and remained above the purported therapeutic threshold (1 ng/mL) from 1 to 24 h postadministration. Repeated daily dosing at 24 and 48 h demonstrated plasma levels above 1 ng/mL for up to 72 h with minimal accumulation or changes in maximal concentrations over time. Inadvertent transfer of the topical drug to nondosed mice in the same cage was evaluated by measuring plasma buprenorphine concentrations in nondosed mice cohoused with a single-dosed mouse. Male mice did not demonstrate transfer of drug via grooming or interactions, yet 2 out of 26 nondosed female mice had detectable buprenorphine plasma levels indicating a relatively low incidence of cross-ingestion in cohoused female mice. This study demonstrates that LA-bup is a promising analgesic in mice that could be used for tailored analgesia strategies, depending on the surgical model or duration of analgesic therapy.

Predictors of medication regimen complexity and its impact on hemoglobin a1c in type 2 diabetes patients: a retrospective analysis in ambulatory care in Makkah City.

Type 2 diabetes mellitus (T2DM) is a widespread chronic disease that poses a significant management challenge due to the complexity of the associated medication regimens, which can have a considerable impact on patient outcomes. Explore the complexity level of diabetes medications among patients with T2DM and to identify the predictors of medication regimen complexity (MRC) and its correlation with hemoglobin A1C (HbA1c) levels. Retrospective, cross-sectional study. An ambulatory care setting of a tertiary hospital in Makkah City, Saudi Arabia. Patients with T2DM referred to the diabetic clinic were identified and assessed for eligibility. The data were collected from patient electronic medical records between October 2022 and September 2023. The MRC Index was used to evaluate the complexity of the patients' medication regimens. MRC index scores and HbA1c levels. 353 records of patients with T2DM. The analysis revealed that 61.8% (n=218) of patients had high MRC, with the dosing frequency contributing significantly to their MRC (mean=3.9, SD=1.9). Having polypharmacy and longstanding T2DM were predictors of high MRC (odds ratios=4.9 and 2.6, respectively; P≤.01). Additionally, there was an inverse association between the patients' diabetes-specific MRC index scores and their glycemic control (odds ratios=0.2, P<.001). The study findings highlight the importance of considering MRC in managing T2DM. Simplifying medication regimens and optimizing medication management strategies can improve patient outcomes. Further research is needed to explore interventions to reduce MRC and enhance diabetes management in this population. Retrospective study design measuring the MRC at a diabetes-specific level.

Formulation, Design, Optimization, and Characterization of Novel Long-acting Injectable Dosage Form of Anti-psychotic Drug

Background: The current research aimed to create and analyze a new long-acting Brexpiprazole (BRX) injectable for successful anti-psychotic drug therapy in order to decrease dosage frequency and increase patient compliance. Systems for drug transport to particular body sites or regulating release rates with accuracy are known as drug delivery systems (DDS). By affixing the drug to a carrier particle like liposomes, nanoparticles, microspheres, etc., which modifies the drug's absorption and release properties, using carrier technology, drugs may be delivered in an intelligent manner. Methods: Utilizing Resomer RG 502 H and RESOMER® RG 752 H extended-release Polymer, Using a quasi-emulsion solvent diffusion, microspheres were made, and emulsification and solvent evaporation process. Results: The produced microspheres were assessed for stability tests, in vitro drug release, flow characteristics, and drug entrapment efficiency. FTIR experiments were used to establish how well the drug excipients worked together. The acarbose microspheres that were created had an 89.9 to 96.1 percent drug entrapment efficiency. The impact of factors like polymer content on medication release was studied. The Stability study of the formulation was carried out under different conditions, and data were established. Comparative pharmacokinetic studies between marketed oral formulation and Brexpirazole microsphere test formulations in Wistar/SD Rats were carried out and concluded. Conclusion: Brexpiprazole (BRX) novel long-acting injectable formulation, could be used effectively for the treatment of mentally challenged anti-psychotic patients worldwide.

Chitosan nanoparticles as drug carrier of gentamicin - density functional theory and molecular dynamics simulation studies

To the best of our knowledge, the detailed evaluation of the interaction of gentamicin with chitosan nanoparticles in the absence and presence of Sodium bis(2-ethylhexyl) sulfosuccinate (AOT) surfactant followed by the evaluation of structural, dynamical, and thermodynamic properties was carried out for the first time which helped to understand the relative drug retention and release time in the model drug delivery system. Gentamicin being an unstable drug molecule demonstrated low efficacy against brucellosis as well as considerable toxicity, thus requiring frequent dosing in different forms including a single dose and combination with other antibiotics; however, no satisfactory result was observed. Chitosan is biodegradable and biocompatible which could help overcome drug delivery issues enabling the drug to reach the target site. Our study is based on the investigation of the chitosan-drug systems without and with the surfactant for the evaluation of the structural, dynamical, and transport properties using a combined approach consisting of density functional theory (DFT) calculations and molecular dynamics (MD) simulations. The DFT results showed that increasing the size of the chain consisting of D-glucosamine facilitated its interaction with the drug molecule thus signifying the role of polymer for the drug accommodation. Furthermore, MD simulation results exhibited the interaction of chitosan nanoparticles with the drug molecules via H-bonding and hydrophobic contacts which were enhanced after the addition of the surfactant. The dynamics and thermodynamic data corroborated the structural properties of the drug-nanoparticle interaction which confirmed the perturbation of the simulation system after the addition of the surfactant. The investigation of another two simulation systems based on the polymer constituents, D-glucosamine pointed towards the significance of the polymerization which eventually resulted in nanoparticles thus providing a platform for drug adsorption. The gentamicin-chitosan nanoparticles were further characterized via transport properties in terms of drug diffusion coefficients which served to consider its use in the context of target drug delivery to treat brucellosis.

Dental and anesthesiology problems in nicotine dependents (literature review)

Nowadays, smoking is one of the significant factors for the development of inflammatory periodontal diseases. The effect of nicotine on the microcirculation is manifested in the deterioration of the trophic level of the gums and a decrease in their resistance to infection. Atrophy of acinar parts of small salivary glands develops and other morphological changes characteristic of progressive sialadenitis occur. A change in the microflora of the oral cavity was found depending on the duration of smoking. Epithelial dysplasia, which covers the entire thickness of the epithelium, but does not affect the connective tissue, is called carcinoma. Worldwide, more than 300 million people use smokeless tobacco. Malignant changes at the site of precancerous diseases occur after a couple of years of using the product. In smokers, nicotine blocks H-cholinergic receptors and reduces sensitivity to local anesthetics. Nicotine promotes the production of the CYP2E1 enzyme, which is responsible for the metabolism of halogen anesthetics: halothane, enflurane, diethyl ether, trichlorethylene, chloroform, isoflurane and methoxyflurane. Chronic smokers show reduced pain tolerance. Before morphine loading, the assessment of pain threshold in nicotine-dependent individuals was significantly lower than in non-smokers. Smokers require higher doses of opiates and benzodiazepines than nonsmokers. Smoking reduces the potency of aminosteroid muscle relaxants, the required doses of vecuronium and rocuronium in smokers were 25 % higher than in patients leading a healthy lifestyle. Smokers also need more frequent doses to maintain neuromuscular block. Quitting smoking 4–6 weeks (ideally 8 weeks) before general anesthesia reduces the frequency of peri- and postoperative complications.