Current Drug Metabolism - Volume 19, Issue 2, 2018

Background: Hyperthermia has been proposed as a promising treatment modality for its advantageous profiles such as mini/non-invasiveness, good tolerability and cost-effectiveness. Quick development of nanotechnology in recent years has greatly broadened the application area of hyperthermia and endowed it with attractive new functions. This review aims to present an overview of different nanostructures mediated hyperthermia in terms of external stimuli source. Methods: We performed to review for the development and current status of nanostructure-mediated hyperthermia, by searching MEDLINE, EMBASE, and Cochrane Library database for identification of relevant articles. Results: In the present study, the systemic results of hyperthermia mediated by nanostructures were researched, and five different kinds of external sources were found and listed in this review. The brief mechanism and commonly explored nanostructures were introduced and then combined therapies of nanostructure-mediated hyperthermia stimulated by different external sources were investigated. Finally, challenges with current nanostructures mediated hyperthermia were discussed in order to give advice to the future development of nanostructure-mediated hyperthermia. Conclusions: Despite all the achievements the new technology of nanostructure-mediated hyperthermia have made in pre-clinical animal experiments, there are still much to be pursued in the further development to be biocompatible, effective and precise.

Background: Nano-oncology and interventional oncology are both rapidly emerging fields in cancer therapies. Synergistic combination of the both fields offers drastic improvements in performance and efficacy of cancer killing agents. Objective: This review is to overview the studies focusing on these two crossing fields and to give an overlook of their future development. Interventional techniques such as selective arterial catheterization, irreversible electroporation (IRE) and radiofrequency ablation (RFA) dramatically enhanced cancer targetability and anticancer efficacy of nanoparticles (NPs). Furthermore, synergistic effects were observed when using different interventional techniques together on NPs directed cancer treatments. On the other hand, NPs improved thermal ablation as well by fundamentally improving heating efficiency, facilitating heat triggered local drug delivery, and increasing cancer control in marginal peri-ablated zones and distant regions. Conclusion: Crossing applications of the both techniques such as percutaneous delivery of near infrared (NIR) into deep tumors by needle insertion and conformal thermal ablation are highly anticipated.

Background: Nanoparticle-based drug delivery systems hold great promise for the treatment of major diseases. However, their slow translation from bench to the clinic posts a concern. It is mainly attributed to the lack of suitable in vitro platforms for rapid and accurate screening of nanomedicine. Recent developments in microfluidic technologies have provided the possibility to reproduce the biomimetic blood vessel microenvironments outside the body, thus offering a convenient means to characterize the in vivo dynamics and biological responses of nanoparticles during circulation. Objective: In this review, we discuss the challenges facing the field of nanoparticle drug delivery and highlight the urgent need for construction of blood-vessel-on-a-chip platforms for testing nanomedicine. We subsequently illustrate advances in fabricating various well-controlled blood-vessel-on-a-chip platforms, covering a few examples that have used such models for evaluating nanoparticle behaviors. We then summarize with conclusions and perspectives. Conclusion: We anticipate that, further development of these blood-vessel-on-a-chip platforms with improved biomimetic parameters, tissue specificity, and personalization, will enable their wide applications in drug screening including nanomedicine.

Background: With the rapid development of nanoparticles in drug delivery system, a lot of interest in the genotoxicity evaluation of nanocarriers has emerged currently. Here our emphasis was placed on the summary of studies on standard genotoxicity assays. Methods: We performed a PubMed/MEDLINE search for all publications in the English language related to assessment of genotoxicity of nanocarriers. A total of 45 publications were included. In these studies, the in vitro and in vivo Comet assay, in vitro and in vivo micronucleus assay, in vitro and in vivo Chromosomal Aberration (CA) assay, Ames test, phosphorylated histone H2Ax (γ-H2Ax) foci formation detection, 8-hydroxy-2'-deoxyguanosine (8-OHdG) assay, Sister Chromatid Exchange (SCE) assay, and mammalian cell mutation assay were all included. Results: We figured out that the results of these assays were apparently inconsistent. More positive results of detecting genotoxicity of nanocarriers were generated via in vitro assays than in vivo assays. Besides, less in vitro positive outcomes turned out in detection of gene mutation than chromosome and DNA damage. Most of the mutagenicity tests for nanocarriers were negative. Conclusion: To sum up, these inconsistent results on genotoxicity of nanocarriers indicate that there are great challenges regarding risk assessment and an urgent need to establishing a battery of standard measurements in the future.

Background: With the development of nanomaterials, nanoparticle-based therapeutics have found increasing application in various fields, including clinical and basic medicine. Real-time monitoring of nanoparticle-based therapeutics is considered critical to both pharmacology and pharmacokinetics. Methods: In this review, we discuss the different methods of real-time monitoring of nanoparticle-based therapeutics comprising different types of nanoparticle carriers, such as metal nanoparticles, inorganic nonmetallic nanoparticles, biodegradable polymer nanoparticles, and biological nanoparticles. Results: In the light of examples and analyses, we conclude that the methods of analysis of the four types of nanoparticle carriers are commonly used methods and mostly not necessary. Under most circumstances, real-time monitoring differs according to nanoparticle type, drugs, diseases, and surroundings. Conclusion: With technology development and advanced researches, there have been increasing measures to track the real-time changes in nanoparticles, and this has led to great progress in pharmacology and therapeutics. However, future studies are warranted to determine the accuracy, applicability, and practicability of different technologies.

Background: In recent years, there has been an unprecedented expansion in the field of nanomedicine with the development of new nanoparticles for the diagnosis and treatment of cancer. It is also known that the use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of ordinarily used compounds in cancer diagnosis and treatment. Objective: Advances in the surface regulating of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future impact involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat or diagnose various kinds of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials than also can combine with thermal treatment. Conclusion: This review examined some mesoporous silica nanoparticles and related nanomaterials and discussed the advantages of using nanocarriers in cancer therapy.

Objective: We aimed at summarizing current evidence about mechanisms for potentially harmful effects of Proton Pump Inhibitors (PPIs). Methods: A Pubmed search was performed, and 207 studies concerning the relationship between use of PPIs and cardiovascular diseases, kidney impairment, nutritional disorders, fractures, infections, functional decline, and mortality were selected and reviewed. Results: PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain. Clinical and epidemiologic evidence is not consistent in regard to some negative outcomes during PPI treatment. Data from randomized clinical trials seem to deny most of them, but they are usually designed to investigate efficacy of drugs in ideal conditions and are not powered enough to detect adverse events. Besides being at special risk of experiencing negative outcomes during long-term treatment with PPIs, older and complex patients treated with polypharmacy regimens are persistently excluded from randomized clinical trials. Thus, large observational studies involving real-world patients should be considered as an important informative source about potential risks related to PPIs. Conclusions: Current evidence suggests that use of PPIs may be associated with negative outcomes by eliciting several different pathophysiologic mechanisms. While short-term PPIs could be considered effective and safe in adult patients with acid-related disorders, their long-term and often inappropriate use in patients carrying vulnerability to adverse events and/or high risk of drug-interactions should be avoided.

Background: In Physiologically Based Pharmacokinetic (PBPK) models, the most important input parameter is tissue-to-plasma partition coefficient (Kp). Over the years, several empirical methods have been developed to predict Kp in animals. Objectives: The objective of this study was to propose two allometric methods to predict Kp from experimentally determined in vivo volume of distribution at steady state (Vss). Method: In one method, Vss was allometrically predicted (using a fixed exponent 1.0 or 0.8) in a given tissue of the rat and then Kp was predicted for that tissue. In another method, an allometric plot (Kp versus Vss) was developed to predict Kp in a tissue of the rat. In total, Kp values were predicted for 46 drugs and 338 tissues. The predicted Kp values by the proposed two methods were compared with the experimentally determined Kp values as well as empirically predicted Kp values by other investigators. Results: Comparison of the predicted Kp values by the two proposed methods with experimentally determined Kp values indicated that 67-72% of the predicted Kp values were within two-fold prediction error. The predictive power or accuracy of method 1 (when taken all tissues and all classes of drugs into account) was 19%, 35%, 14%, 35%, 14%, and 13% better than the methods proposed by Arundel, Berezhkovskiy, Jansson et al., Poulin et al., Poulin- Theil, and Rodgers et al. respectively. Conclusion: The proposed two allometric methods are slightly more accurate than other empirical methods in their predictive performance for the prediction of tissue Kp values for acidic, weak bases and neutral drugs.