Development of intestinal colonic drug delivery systems for diverticular disease: A QbD approach.

This study aimed to advance the development of intestinal colon-coated sustained-release matrix tablets of metronidazole for diverticulitis treatment, employing the Quality by Design (QbD) methodology. Comprehensive Risk analysis and Risk evaluation were conducted to assess the potential risks associated with Critical Material Attributes (CMA) and Critical Process Parameters (CPP). Ishikawa diagram, color-coded risk classification and the Risk Priority Number (RPN) were used as tools for risk evaluation.

Dosing Evaluation of Ceftazidime-Avibactam in Intensive Care Unit Patients Based on Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling and Simulation.

is the most common microorganism involved in many ICU-acquired infections. A correct dosage regimen is pivotal to avoiding resistance development, worse outcomes and higher mortality rates. The aim of this study was to perform a pharmacokinetic-pharmacodynamic (PK/PD) evaluation of recommended dosing regimens of ceftazidime-avibactam (CAZ-AVI) in ICU patients with different degrees of renal function for a specific strain of .

Model-Informed Precision Dosing (MIPD).

Model-informed precision dosing (MIPD) is an advanced quantitative approach focusing on individualized dosage optimization, integrating complex mathematical and statistical models of drugs and disease combined with individual demographic and clinical patient characteristics [...

Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK.

Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria.

Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution.

Computational modelling has gained attention for evaluating nanoparticle-based drug delivery systems. Physiologically based pharmacokinetic (PBPK) modelling provides a mechanistic approach for evaluating drug biodistribution. The aim of this work is to develop a specific PBPK model to simulate stavudine biodistribution after the administration of a 40 nm gold nanoparticle-based drug delivery system in rats.

Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin.

This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for the evaluated amikacin dosing guidelines together with a significant impact of albumin concentrations on efficacy and safety.

Recent advances in functionalized nanomaterials for the diagnosis and treatment of bacterial infections.

The growing problem of resistant infections due to antibiotic misuse is a worldwide concern that poses a grave threat to healthcare systems. Thus, it is necessary to discover new strategies to combat infectious diseases. In this review, we provide a selective overview of recent advances in the use of nanocomposites as alternatives to antibiotics in antimicrobial treatments.

Cell-Based Drug Delivery Platforms.

Within the framework of nanomedicine, drug delivery has experienced rapid progress in recent years [...

Advances in Exosomes-Based Drug Delivery Systems.

Exosomes, a subgroup of extracellular vesicles, are important mediators of long-distance intercellular communication and are involved in a diverse range of biological processes such as the transport of lipids, proteins, and nucleic acids. Researchers, seeing the problems caused by the toxic effects and clearance of synthetic nanoparticles, consider exosomes as an interesting alternative to such nanoparticles in the specific and controlled transport of drugs. In recent years, there have been remarkable advances in the use of exosomes in cancer therapeutics or for treating neurological diseases, among other applications.

Recent advances in colon drug delivery systems.

As a result of its ability to target certain drugs and/or peptides to the colonic region for the treatment of several diseases while avoiding systemic absorption and potential side effects, colon drug delivery has become a field of research of growing interest. Developing new pharmaceutical formulations capable of reaching the colon requires a broad knowledge of natural and synthetic/semisynthetic polymers. Chitosan, polyethylene-oxide, hydroxypropyl methylcellulose, pectin, natural gums, alginates and polymethacrylates have shown promise when applied in the development of colon drug delivery systems, which range from classic formulation strategies such as tablets and capsules to more sophisticated approaches like nanosystems and integrated osmotic-like formulations.

Amikacin initial dosage in patients with hypoalbuminaemia: an interactive tool based on a population pharmacokinetic approach.

Objectives: To characterize amikacin population pharmacokinetics in patients with hypoalbuminaemia and to develop a model-based interactive application for amikacin initial dosage.

Methods: A population pharmacokinetic model was developed using a non-linear mixed-effects modelling approach (NONMEM) with amikacin concentration-time data collected from clinical practice (75% hypoalbuminaemic patients). Goodness-of-fit plots, minimum objective function value, prediction-corrected visual predictive check, bootstrapping, precision and bias of parameter estimates were used for model evaluation.

Targeting of Hepatic Macrophages by Therapeutic Nanoparticles.

Hepatic macrophage populations include different types of cells with plastic properties that can differentiate into diverse phenotypes to modulate their properties in response to different stimuli. They often regulate the activity of other cells and play an important role in many hepatic diseases. In response to those pathological situations, they are activated, releasing cytokines and chemokines; they may attract circulating monocytes and exert functions that can aggravate the symptoms or drive reparation processes.

Enteric coating of oral solid dosage forms as a tool to improve drug bioavailability.

Enteric coating is a common procedure in the development of oral pharmaceutical dosage forms. The main advantage of enteric coating is that it protects the drug from acidic pH and enzymatic degradation in the stomach while protecting it from the undesirable effects of some drugs. There is certain controversy regarding the real influence of enteric coating on the bioavailability of many drugs.

Evaluation of renal function equations to predict amikacin clearance.

: To evaluate the predictive performance of eight renal function equations to describe amikacin elimination in a large standard population with a wide range of age. : Retrospective study of adult hospitalized patients treated with amikacin and monitored in the clinical pharmacokinetics laboratory of a pharmacy service. Renal function was calculated as Cockcroft-Gault with total, adjusted and ideal body weight, MDRD-4, CKD-EPI, rLM, BIS1, and FAS.

Nanoparticles for Signaling in Biodiagnosis and Treatment of Infectious Diseases.

Advances in nanoparticle-based systems constitute a promising research area with important implications for the treatment of bacterial infections, especially against multidrug resistant strains and bacterial biofilms. Nanosystems may be useful for the diagnosis and treatment of viral and fungal infections. Commercial diagnostic tests based on nanosystems are currently available.

Pharmacokinetics and dosing requirements of digoxin in pregnant women treated for fetal supraventricular tachycardia.

Background: The objective of this study was to characterize the pharmacokinetics (PK) of digoxin in pregnant women and its potential implications for drug dosing.

Methods: Serum digoxin concentrations (SDCs) obtained in pregnant women treated for fetal supraventricular tachycardia (SVT) was retrospectively collected. PK analysis was comparatively performed using a two-stage approach (PKS™) and a Population PK approach (NONMEM™).

Gold Nanocarriers for Macrophage-Targeted Therapy of Human Immunodeficiency Virus.

The human immunodeficiency virus (HIV) continues to be a global pandemic and there is an urgent need for innovative treatment. Immune cells represent a major target of virus infection, but are also therapeutic targets. Currently, no antiretroviral therapy targets macrophages, which function as portal of entry and as major long-term deposit of HIV.

Drug-loaded erythrocytes: on the road toward marketing approval.

Erythrocyte drug encapsulation is one of the most promising therapeutic alternative approaches for the administration of toxic or rapidly cleared drugs. Drug-loaded erythrocytes can operate through one of the three main mechanisms of action: extension of circulation half-life (bioreactor), slow drug release, or specific organ targeting. Although the clinical development of erythrocyte carriers is confronted with regulatory and development process challenges, industrial development is expanding.

Current applications of nanoparticles in infectious diseases.

For decades infections have been treated easily with drugs. However, in the 21st century, they may become lethal again owing to the development of antimicrobial resistance. Pathogens can become resistant by means of different mechanisms, such as increasing the time they spend in the intracellular environment, where drugs are unable to reach therapeutic levels.

Approaches for dosage individualisation in critically ill patients.

Introduction: Pharmacokinetic variability in critically ill patients is the result of the overlapping of multiple pathophysiological and clinical factors. Unpredictable exposure from standard dosage regimens may influence the outcome of treatment. Therefore, strategies for dosage individualisation are recommended in this setting.

Evaluating amikacin dosage regimens in intensive care unit patients: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objectives of this study were to conduct a comparative pharmacokinetic/pharmacodynamic (PK/PD) evaluation using Monte Carlo simulation of conventional versus high-dose extended-interval dosage (HDED) regimens of amikacin (AMK) in intensive care unit (ICU) patients for an Acinetobacter baumannii infection model. The simulation was performed in five populations (a control population and four subpopulations of ICU patients). Using a specific AMK PK/PD model and Monte Carlo simulation, the following were generated: simulated AMK steady-state plasma level curves; PK/PD efficacy indexes [time during which the serum drug concentration remains above the minimum inhibitory concentration (MIC) for a dosing period (%T>MIC) and ratio of peak serum concentration to MIC (Cmax/MIC)]; evolution of bacterial growth curves; and adaptive resistance to treatment.

Cell-based drug-delivery platforms.

Cell systems have recently emerged as biological drug carriers, as an interesting alternative to other systems such as micro- and nano-particles. Different cells, such as carrier erythrocytes, bacterial ghosts and genetically engineered stem and dendritic cells have been used. They provide sustained release and specific delivery of drugs, enzymatic systems and genetic material to certain organs and tissues.

International seminar on the red blood cells as vehicles for drugs.

The first human transfusion was performed by the pioneer Dr Jean-Baptiste Denis in France in 1667 and now, three centuries later, around 50 millions blood units are transfused every year, saving millions of lives. Today, there is a new application for red blood cells (RBCs) in cellular therapy: the effective use of erythrocytes as vehicles for chemical or biological drugs. Using this approach, the therapeutic index of RBC-entrapped molecules can be significantly improved with increased efficacy and reduced side effects.

Critical factors in the release of drugs from sustained release hydrophilic matrices.

Hydrophilic matrix systems are one of the most interesting drug delivery systems, and they are currently some of the most widely used to control the release rate of drugs. There are too much factors involved in drug release from hydrophilic matrix systems. The most important factors to be taken into account when developing a formulation based on hydrophilic matrices are the percentage, solubility and drug particle size; the type of polymer, the percentage incorporated, its degree of viscosity and the polymer particle size.

Optimization of release kinetics from sustained-release formulations using model-independent pharmacokinetic simulation.

In the present work, a single model-independent approach was developed to optimize the release kinetics of drugs from sustained-release formulations, using stavudine (d4T) as a model drug. This approach is based on the pharmacokinetic simulation of drug plasma levels through a semiparametric approach of the input function and on convolution with an empirical polyexponential unit impulse response function. Input functions were evaluated using different zero-order and first-order release constants.