In recent years, a great deal of interest has been focused on the development of novel atomic force microscopy (AFM)-based methods. From first being an unstable method, AFM has emerged as the perfect tool for the study of phenomena at the nanoscale, which includes quantitative single molecule studies. Numerous novel AFM methods play a crucial role in the invention of novel drugs, their delivery systems, based on either polymers or inorganic/metallic matrices, and in the examination of disease-related tissue changes. Such contemporary progressive studies are a perfect example of interdisciplinary research, which results in exemplary findings and discoveries. This review focuses especially on the literature published in the last decade; however the most important earlier discoveries are also included.
COBISS.SI-ID: 19422230
Nanofibers represent an attractive novel drug delivery system for prolonged release. However, sustained release of hydrophilic drugs, like ciprofloxacin hydrochloride (CIP), from polymeric nanofibers is not an easy task. The present study investigates the effect of different hydrophobic polymers (PCL and PMMA) alone in monolithic nanofibers, or with hydrophilic polymers (PVA, PEO, and chitosan) in blended nanofibers aiming to achieve sustained CIP release. CIP release from PCL nanofibers was 46% and from PMMA just 1.5% over 40 day period. Thus, PMMA holds great promise for modification of CIP release from blended nanofibers. PMMA blends with 10% PEO, PVA or chitosan were used to electrospin nanofibers from solution in the mixture of acetic and formic acid. These nanofibers exhibited different drug-release profiles: PEO containing nanofiber mats demonstrated high burst effect, chitosan containing mats revealed very slow gradual release, and PVA containing mats yielded smaller burst effect with favorable sustained release. We have also shown that gradual sustain release of antibiotic like CIP can be additionally tuned over 18 days with various blend ratios of PMMA with PVA or chitosan reaching almost 100%. Mathematical model in agreement with the experimental observation revealed that the sustained CIP release from the blended nanofiber corresponded to the two-stage desorption process.
COBISS.SI-ID: 3989361
This study aimed to develop a population pharmacokinetic model for quantitative evaluation of the influence of genetic variants in metabolic enzymes and transporters on lamotrigine pharmacokinetics while taking into account the influence of various clinical, biochemical and demographic factors. We included 100 patients with epilepsy on stable dosing with lamotrigine as mono or adjunctive therapy. Lamotrigine and lamotrigine N-2-glucuronide concentrations were determined in up to two plasma samples per patient. Patients were genotyped for UGT1A4, UGT2B7, ABCB1, and SLC22A1. Population pharmacokinetic analysis was performed by nonlinear mixed effects modelling. Prior knowledge from previous pharmacokinetic studies was incorporated to stabilize the modelling process. A parent-metabolite model was developed to get a more detailed view on the covariate effects on lamotrigine metabolism. With a base model absorption rate (interindividual variability) was estimated at 1.96%h-1 (72.8%), oral clearance at 2.32%L/h (41.4%) and distribution volume at 77.6%L (30.2%). Lamotrigine clearance was associated with genetic factors, patient's weight, renal function, smoking and co-treatment with enzyme inducing or inhibiting drugs. In patients with UGT2B7 -161TT genotype clearance was lower compared to GT and GG genotypes. Clearance was particularly high in patients with UGT2B7 372 GG genotype (compared to AA genotype it was 117%; 95% CI: 44.8-247% higher). Variability in lamotrigine pharmacokinetics is large and quantification of its sources may lead to more precise individual treatment. Genotyping for UGT2B7 may be useful in various clinical settings.
COBISS.SI-ID: 4065137
Background: Incidence of drug-drug interactions (DDIs) increases with complexity of treatment and comorbidities, as in heart failure (HF). This randomized, double-blind study evaluated the intervention of the pharmacist onprevalence of clinically relevant DDIs (NCT01855165). Methods: Patients admitted with HF were screened for clinically relevant DDIs, and randomized to control or intervention. All attending physicians received standard advice about pharmacological therapy; those in the intervention group also received alerts about clinically relevant DDIs. Primary endpoint was DDI at discharge and secondary were re-hospitalization or death during follow-up. Results: Of 213 patients, 51 (mean age, 79Ž6 years;male, 47%) showed 66 clinically relevant DDIs and were randomized. For intervention (n=26) versus control (n =25), the number of patients with and the number of DDIs were significantly lower at discharge: 8 vs. 18 and 10 vs. 31; p=0.003 and 0.0049, respectively. Over a 6 month follow-up period, 11 control and 9 intervention patients were re-hospitalized or died (p N 0.2 for all). No significant differences were seen between control and intervention for patients with eGFR b60 mL/min/1.73 m2 (78%) for re-hospitalization or death (10 vs. 7; p = 0.74). Conclusions: Pharmacist intervention significantly reduces the number of patients with clinically relevant DDIs, but not clinical endpoints 6 months from discharge.
COBISS.SI-ID: 3979889
Background: Guidelines on suggested pharmacological treatments for heart failure (HF) are not optimally implemented in clinical practice and whether pharmacotherapy adjustment actually happens in daily practice is largely unknown. We aimed to investigate pharmacotherapy modifications during hospitalization. Methods: This was a prospective observational survey where all admissions were screened for HF; 210 patients were included. The guideline adherence index (GAI) and modified GAI (mGAI, if )- 50% of target dose) were used to grade the pharmacotherapy. Results: Among 198 patients discharged alive (mean age 77 years, 51% male), 49% had preserved left ventricular ejection fraction (PLVEF) and 30% had left ventricular systolic dysfunction (LVSD); the echocardiography report was unavailable for 21%. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists were prescribed to 78%, 58% and 20% of patients on admission and 72%, 65% and 23% at discharge, respectively. Overall, 14% of patients met GAI-3, but at discharge only 7% met mGAI-3. One of the key drugs was stopped or down-titrated in 27%. During follow-up, 21% of patients died (25% with LVSD). Patients with LVSD discharged with at least one HF drug had a lower risk of death than patients with none (HR = 0.142, 95% CI = 0.029-0.683, p = 0.015). Patients with PLVEF had better prognosis than LVSD patients when no HF drugs were prescribed at discharge (HR = 0.075, 95% CI = 0.009-0.627, p = 0.017). Conclusions: The pharmacotherapy of HF patients did not improve significantly during hospitalization, remaining suboptimal. Treatment with key drugs was terminatedor reduced in a significant proportion of patients, mostly without specific written justification.
COBISS.SI-ID: 4011889