At nanoscale, man-made materials may show unique properties that differ from bulk and dissolved counterparts. The unique properties of engineered nanomaterials not only impart critical advantages but also confer toxicity because of their unwanted interactions with different biological compartments and cellular processes. In this review, we discuss various entry routes of nanomaterials in the human body, their applications in daily life, and the mechanisms underlying their toxicity. We further explore the passage of nanomaterials into air, water, and soil ecosystems, resulting in diverse environmental impacts. Briefly, we probe the available strategies for risk assessment and risk management to assist in reducing the occupational risks of potentially hazardous engineered nanomaterials including the control banding (CB) approach. Moreover, we substantiate the need for uniform guidelines for systematic analysis of nanomaterial toxicity, in silico toxicological investigations, and obligation to ensure the safe disposal of nanowaste to reduce or eliminate untoward environmental and health impacts. At the end, we scrutinize global regulatory trends, hurdles, and efforts to develop better regulatory sciences in the field of nanomedicines.

In vitro drug release testing is an important quality control tool for formulation development. However, the literature has evidence that poly-lactide-co-glycolide (PLGA)-based formulations show a slower in vitro drug release than a real in vivo drug release. Much longer in vitro drug release profiles may not be reflective of real in vivo performances and may significantly affect the timeline for a formulation development. The objective of this study was to develop a surfactant mediated accelerated in vitro drug release method for the PLGA nanoparticles (NPs) of a novel chemotherapeutic agent AC1LPSZG, a model drug with a poor solubility. The Sotax USP apparatus 4 was used to test in vitro drug release in a phosphate buffer with a pH value of 6.8. The sink conditions were improved using surfactants in the order of sodium lauryl sulfate (SLS) < Tween 80 < cetyltrimethylammonium bromide (CTAB). The dissolution efficiency (DE) and area under the dissolution curve (AUC) were increased three-fold when increasing the CTAB concentration in the phosphate buffer (pH 6.8). Similar Weibull release kinetics and good linear correlations (R²~0.99) indicated a good correlation between the real-time in vitro release profile in the phosphate buffer (pH 6.8) and accelerated release profiles in the optimized medium. This newly developed accelerated and discriminatory in vitro test can be used as a quality control tool to identify critical formulation and process parameters to ensure a batch-to-batch uniformity. It may also serve as a surrogate for bioequivalence studies if a predictive in vitro in vivo correlation (IVIVC) is obtained. The results of this study are limited to AC1LPSZG NPs, but a similar consideration can be extended to other PLGA-based NPs of drugs with similar properties and solubility profiles.

Preparation and Physicochemical Characterization of Tizanidine Hydrochloride Nanoparticles

Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC–MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3 min per sample. A linear dose–response for quantification was observed over the range of 10–5000 ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87–102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6 h after collection and stored at −80 °C until analysis within 30 days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.

The clinical success of investigational pharmaceuticals remains doubtful due to an unacceptable level of attrition during clinical drug development and declining clinical approval rates. Countless molecules are being withdrawn during drug discovery and clinical trial phases due to poor pharmacokinetics (ADME), lack of safety and efficacy, commercial interests, market competition, and patent protection expiry. Consequently, the novel drug pipelines are running dry. Because huge capital is involved in different clinical trial phases, the task of bringing a new drug or drug formulation to the market is a very costly venture. Running a clinical trial is a complex, expensive, and time-intensive project. It is often tedious and troublesome to change a study design after its inception; thus, it is necessary to design the study for easy and comprehensive data analysis and interpretation. Cohort, cross-sectional, and case-control studies, collectively touted as observational studies, provide an option for solving clinical problems when a randomized controlled trial (RCT) is not feasible due to time, money, or ethical restraints. This review article presents three prime observational research methodologies using relevant examples, common causes of spurious results, and ways to trivialize their impacts, including the most popular indices for measuring clinical relevance of the treatment effects. The article also explores attrition issues and issues related to the improvement of clinical approval success, with an emphasis on possible applications of drug delivery technologies to salvage drug molecules.