Type 2 diabetes: an exploratory genetic association analysis of selected metabolizing enzymes and transporters and effects on cardiovascular and renal biomarkers.

OBJECTIVES: This study sought to identify potential pharmacogenetic associations of selected enzymes and transporters with type 2 diabetes (T2D). In addition, pharmacogenomic profiles, concentrations of asymmetric dimethylarginine (ADMA) or kidney injury molecule-1 (KIM-1), and several covariates were investigated. METHODS: Whole blood was collected from 63 patients, with 32 individuals with T2D. A pharmacogenomic panel was used to assay genetic profiles, and biomarker ELISAs were run to determine subject concentrations of ADMA and KIM-1. Additive genetic modeling with multiple linear and logistic regressions were performed to discover potential SNPs-outcome associations using PLINK. RESULTS: Ten SNPs were found to be significant (p<0.05) depending on the inclusion or exclusion of covariates. Of these, four were found in association with the presence of T2D, rs2231142, rs1801280, rs1799929, and rs1801265 depending on covariate inclusion or exclusion. Regarding ADMA, one SNP was found to be significant without covariates, rs1048943. Five SNPs were identified in association with KIM-1 and T2D in the presence of covariates, rs12208357, rs34059508, rs1058930, rs1902023, and rs3745274. Biomarker concentrations were not significantly different in the presence of T2D. CONCLUSIONS: This exploratory study found several SNPs related to T2D; further research is required to validate and understand these relationships.

Association between smoking status and homocysteine levels and possible effect modification by cholesterol and oestradiol.

Introduction: This study aimed to examine the association of smoking status with homocysteine levels and to determine whether the association is modified by oestradiol or cholesterol.Methods: Data (N = 4580) were obtained from National Health and Nutrition Examination Survey 2003-2004 with analysis done in 2018 on adults aged ≥20 years. The outcome was homocysteine; smoking status was the exposure variable and categorized as current, former or never smoker. Generalized linear models were used to examine the associations between smoking status and homocysteine levels, while assessing the impact of oestradiol and cholesterol.Results: After adjusting for age, sex, ethnicity, education and income level, homocysteine levels did differ by smoking status ((current smokers versus never smokers: ß: 0.18 CI: 0.00, 0.36), (former smokers: ß: 0.10 CI: -0.09, 0.28)). The addition of oestradiol as an interaction term in adjusted models was associated with a 16.6% increase in homocysteine levels when compared to models without the interaction term. Oestradiol but not cholesterol did moderate the association between smoking status and homocysteine levels.Discussion and conclusions: Homocysteine levels did differ across smoking status after adjusting for confounders. Oestradiol did moderate the relationship between homocysteine and smoking status.

Opioids: A Review of Pharmacokinetics and Pharmacodynamics in Neonates, Infants, and Children.

Pain management in the pediatric population is complex for many reasons. Mild pain is usually managed quite well with oral acetaminophen or ibuprofen. Situations involving more severe pain often require the use of an opioid, which may be administered by many different routes, depending on clinical necessity. Acute and chronic disease states, as well as the constantly changing maturational process, produce unique challenges at every level of pediatrics in dosing and management of all medications, especially with regard to high-risk opioids. Although there has been significant progress in the understanding of opioid pharmacokinetics and pharmacodynamics in neonates, infants, children, and adolescents, somewhat limited data exist from which necessary information, concerning the safe and effective use of these agents, may be drawn. The evidence here provided is intended to be helpful in directing the practitioner to patient-specific reasons for preferring one opioid over another. As our knowledge of opioids and their effects has grown, it has become clear that older medications like codeine and meperidine (pethidine) have very limited use in pediatrics. This review provides pharmacokinetic and pharmacodynamic evidence on the currently available opioids: morphine, fentanyl (and derivatives), codeine, meperidine, oxycodone, hydrocodone, hydromorphone, methadone, buprenorphine, butorphanol, nalbuphine, pentazocin, ketobemidone, tramadol, piritramide, naloxone and naltrexone. Morphine, being the most studied opioid analgesic, is the standard against which all others are compared. Pharmacokinetic parameters of morphine that have been found in neonates, i.e., higher volume of distribution, immature metabolic processes that develop at various rates, elimination that is variable based on age and weight, as well as treated and untreated disease processes, are an example of all opioids in the population discussed in this review. Outside the premature and neonatal population, the use of opioids in infants, children, and adolescents quickly begins to resemble the established values found in adults. As such, the concerns (risks) of these medications become comparable to those seen in adults.

Faculty Applicants' Attempt to Inflate CVs Using Predatory Journals.

Recently, scientific publishing has experienced an expansion of journals and publishers whose primary goal is profit and whose peer review process is virtually non-existent. These "predatory" or "opportunistic" journals pose a threat to the credibility and integrity of legitimate scientific literature, and quality science. Unfortunately, many scientists choose to publish in these journals and/or serve on their editorial boards, either due to ease of rapid publication or naivety. Here, we highlight the extensive use of predatory publications or editorial board involvement by applicants applying for a faculty position in the Pharmaceutical Sciences department at the Bill Gatton College of Pharmacy at East Tennessee State University. We caution search committees at other pharmacy schools to thoroughly examine applicant curricula vitarum (CVs) for predatory publishing.

HIV Integrase Inhibitor Pharmacogenetics: An Exploratory Study.

BACKGROUND AND OBJECTIVES: Integrase strand transfer inhibitors (INSTIs), dolutegravir, elvitegravir, and raltegravir, have become integral in the treatment of HIV, with close monitoring of continued efficacy and tolerability. As side effect occurrence varies among subjects receiving these drugs, we sought to perform an exploratory analysis examining the role of several single-nucleotide polymorphisms (SNPs) on drug concentration changes, selected clinical outcomes, and the occurrence of subject-reported adverse events. METHODS: Adults (aged ≥ 18 years) receiving INSTI-based regimens for treatment of HIV were recruited and genotyped with an iPLEX ADME PGx Pro v1.0 Panel. Multiple linear or logistic regression with covariates [age, sex, BMI, regimen (in the across-regimen group), regimen duration, and baseline variables (for continuous parameters)] was used to detect significant (p < 0.05) association of selected clinical data with genetic variants within the study population. RESULTS: In a sample (n = 88) with a median age of 52.5 years (IQR 45.7-57.2) being predominately Caucasian (88.6%) and male (86.4%), this exploratory study discovered several associations between variables and SNPs, when using INSTIs. Abnormal dream occurrence was statistically different (p = 0.028) between regimens. Additionally, several SNPs were found to be associated with adverse event profiles primarily when all regimens were grouped together. CONCLUSION: The associations found in this study point to a need for further assessment, within the population living with HIV, of factors contributing to unfavorable subject outcomes. These exploratory findings require confirmation in larger studies, which then may investigate pharmacogenetic mechanisms.

The associated risk factors for coronary artery calcium in asymptomatic individuals with and without diabetes in rural Central Appalachia.

AIM: To examine the risk factor of coronary artery calcium (CAC) in individuals with diabetes and those without diabetes in Central Appalachia. METHODS: Study population included 2479 asymptomatic participants who underwent CAC screening between August 2012 and November 2016. CAC score was classified into four categories [0 (no plaque), 1-99 (mild plaque), 100-399 (moderate plaque), and ≥400 (severe plaque)]. Multinomial logistic regression analyses were conducted to test the association between CAC and cardiovascular disease (CVD) risk factors among participants with diabetes, age and gender matched controls, and randomly selected controls. RESULTS: 13.6% of total participants had diabetes. Around 69%, 59.8%, and 57.7% of the participants with diabetes, matched controls, and randomly selected controls had CAC score ≥1, respectively. Participants with diabetes had higher prevalence of all CVD risk factors than controls. Among participants with diabetes, hypertension and physical inactivity increased the odds of CAC = 100-399, while among those without diabetes, hypertension and hypercholesteremia increased the odds of having CAC = 1-99 and CAC ≥ 400. CONCLUSION: Half of study participants had subclinical atherosclerosis (i.e., CAC), and individuals with diabetes had higher CAC scores. This study suggests that individuals with diabetes in Central Appalachia might benefit from screening for CAC.

Abuse-Deterrent Opioid Formulations: A Key Ingredient in the Recipe to Prevent Opioid Disasters?

The US Food and Drug Administration (FDA) is encouraging the innovation of long-acting opioid formulations that are manipulation-resistant. The purpose of this commentary is to assess the benefits and limitations of abuse-deterrent opioid formulations (ADFs) and discuss their role in mitigating the current opioid epidemic. ADFs have been created with chemical properties that make it difficult for people who non-medically use prescription drugs to crush and dissolve opioid tablets, as well as by combining opioids with antagonists such as naloxone or naltrexone, which are released only when the dosage form has been manipulated or the drug is taken by a non-intended route. Despite these and other technologies, consensus regarding the effectiveness of these formulations in preventing non-medical use is lacking given the difficulty in obtaining post-marketing data. Researchers also question if the creation of abuse-deterrent drugs will have a positive effect on those struggling with a severe opioid-use disorder, fearing that current opioid users will simply find a new - perhaps more dangerous - drug of choice. Abuse-deterrent opioids are still opioids, and although they may make manipulation more difficult than non-ADF formulations, they are not "abuse proof." The introduction of ADFs could provide a false sense of security among prescribers and dispensers, and we fear that ADFs may have a minimal impact on non-medical use of prescription opioids. Further epidemiological studies will be required to determine the large-scale impact of abuse-deterrent opioids in preventing opioid use disorder and its downstream consequences.

Analysis of PTPRK polymorphisms in association with risk and age at onset of Alzheimer's disease, cancer risk, and cholesterol.

The human receptor-type protein-tyrosine phosphatase kappa (PTPRK) gene is highly expressed in human brain and was previously associated with an increased risk of neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in PTPRK with the risk and age at onset (AAO) of Alzheimer's disease (AD) in 791 AD patients and 782 controls. Our data analysis showed that five SNPs (top SNP rs4895829 with p = 0.0125) were associated with the risk of AD based on a multiple logistic regression (p < 0.05); while six SNPs (top SNP rs1891150 with p = 8.02 × 10-6) were associated with AAO by using a multiple linear regression analysis. Interestingly, rs2326681 was associated with both the risk and AAO of AD (p = 4.65 × 10-2 and 5.18 × 10-3, respectively). In a replication study, the results from family-based association test - generalized estimating equation (GEE) statistics and Wilcoxon test showed that seven SNPs were associated with the risk of AD (top SNP rs11756545 with p = 1.02 × 10-2) and 12 SNPs were associated with the AAO (top SNP rs11966128 with p = 1.39 × 10-4), respectively. One additional sample showed that four SNPs were associated with risk of cancer (top SNP rs1339197 with p = 4.1 × 10-3), 12 SNPs associated with LDL-cholesterol (top SNP rs4544930 with p = 3.47 × 10-3), and eight SNPs associated with total cholesterol (top SNP rs1012049 with p = 6.09 × 10-3). In addition, the AD associated rs4895829 was associated with the gene expression level in the cerebellum (p = 7.3 × 10-5). The present study is the first study providing evidence of several genetic variants within the PTPRK gene associated with the risk and AAO of AD, risk of cancer, LDL and total cholesterol levels.

Quantification of two isomeric flavones in rat colon tissue using reverse phase high performance liquid chromatography.

BACKGROUND: Antineoplastic activity has been previously shown for two isomeric flavones, 5,7-dihydroxy-3,6,8-trimethoxy flavone (flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy flavone (flavone B), against colon cancer cell lines (Thomas et al. in PLoS ONE 7:e39806, 5). Here, we present modified methods for the extraction and quantification of flavones A and B in rat colon tissue after intravenous dosing via high performance liquid chromatography, from the originally described procedure for extraction and quantification in rat plasma (Whitted et al. in J Chromatogr B Analyt Technol Biomed Life Sci 1001:150-155, 7). RESULTS: Modifications included tissue homogenization (1 g tissue: 2 mL water), filtration of the supernatant with a PVDF membrane, and the use of only one calibration curve to determine the concentration of each flavone in colon tissue. Good separation was achieved and representative equations were linear with r 2  ≥ 0.99 for both flavones. Precision and accuracy for flavone A ranged from 0.88-24.03 and 109-116%. Precision and accuracy for flavone B ranged from 1.62-33.56 and 98-113%. Concentrations of 1639 ± 601 ng/g flavone A and 5975 ± 2480 ng/g of flavone B were detected in rat colon tissue 6 h post dosing. CONCLUSIONS: Modifications to the extraction methods for flavone A and flavone B from rat colon tissue had good separation, precision, and accuracy.

Isavuconazonium sulfate: a triazole prodrug for invasive fungal infections.

OBJECTIVE: To review the place in therapy of isavuconazole, the active metabolite of isavuconazonium sulfate, via a review of the available literature on drug chemistry, spectrum of activity, pharmacokinetic/pharmacodynamic profile and trials assessing clinical efficacy and safety. METHODS: Relevant data, original research articles and reviews, were gathered primarily through the use of a PubMed database search. The search was conducted without date restrictions in order to collect both historical and recent data regarding isavuconazole. KEY FINDINGS: Isavuconazole is a triazole currently approved not only for use in invasive aspergillosis and mucormycosis but also has demonstrable activity against Candida species and other common fungal pathogens. This drug has features which make it more clinically appealing compared to other azoles with similar indications. In specific, isavuconazole does not require a cyclodextrin vehicle due to its water solubility, and at present, does not require therapeutic drug monitoring. Moreover, isavuconazole has displayed improved safety and tolerability compared to voriconazole. Available data from Phase III clinical trials shows isavuconazole to be a possible therapeutic option to currently available therapies for which it is approved; however, clinical conclusions should be reserved until results have been published and more data from clinical use is reported. CONCLUSIONS: Isavuconazole is a new triazole with broad-spectrum antifungal activity including invasive aspergillosis and mucormycosis.

Polymorphisms in PDLIM5 gene are associated with alcohol dependence, type 2 diabetes, and hypertension.

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in alcohol dependence (AD), bipolar disorder, and major depressive disorder; however, no study has identified shared genetic variants within PDLIM5 gene among AD, type 2 diabetes (T2D), and hypertension. This study investigated the association of 72 single nucleotide polymorphism (SNPs) with AD (1066 AD cases and 1278 controls) in the Study of Addiction - Genetics and Environment (SAGE) sample and 47 SNPs with T2D (878 cases and 2686 non-diabetic) and hypertension (825 cases and 2739 non-hypertensive) in the Marshfield sample. Multiple logistic regression models in PLINK software were used to examine the associations of genetic variants with AD, T2D, and hypertension and SNP x alcohol consumption interactions for T2D and hypertension. Twenty-five SNPs were associated with AD in the SAGE sample (p < 0.05); rs1048627 showed the strongest association with AD (p = 5.53 × 10-4). Of the 25 SNPs, 5 SNPs showed associations with both AD in the SAGE sample and T2D in the Marshfield sample (top SNP rs11097432 with p = 0.00107 for T2D and p = 0.0483 for AD) while 6 SNPs showed associations with both AD in the SAGE sample and hypertension in the Marshfield sample (top SNP rs12500426 with p = 0.0119 for hypertension and p = 1.51 × 10-3 for AD). SNP (rs6532496) showed significant interaction with alcohol consumption for hypertension. Our results showed that several genetic variants in PDLIM5 gene influence AD, T2D and hypertension. These findings offer the potential for new insights into the pathogenesis of AD, T2D, and hypertension.

A descriptive investigation of the impact of student research projects arising from elective research courses.

BACKGROUND: Pharmacy academicians have noted the need to develop research skills in student pharmacists. At the Gatton College of Pharmacy, significant focus has been placed on the development of research skills through offering elective research courses. In order to evaluate the impact of participation in the research elective(s), we analyzed college records and surveyed faculty members with regard to the number of poster/podium presentations, published peer-reviewed manuscripts, and funded projects. RESULTS: Student enrollment in the research elective sequence has increased over time and has resulted in 81 poster presentations, 14 podium presentations, and 15 peer-reviewed publications. CONCLUSIONS: Implementation of a research elective sequence and fostering of a research culture amongst the faculty and students has resulted in increased student engagement in research and related scholarly activities.

Histopathology and oxidative stress analysis of concomitant misoprostol and celecoxib administration.

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to non-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 µg/kg misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a vehicle dose of one group and one group received celecoxib in addition to misoprostol. Livers were harvested on day 10. No hepatic abnormalities were observed denoting a lack of influence by either drug. Also no change in mean biomarker levels was detected. The changes in hepatic celecoxib concentration in the misoprostol-receiving group compared to control were not significant. Thus misoprostol does not influence hepatic celecoxib effects in terms of histopathology, oxidative stress, or celecoxib concentration level at the dosage and duration examined.

Development of reversed-phase high performance liquid chromatography methods for quantification of two isomeric flavones and the application of the methods to pharmacokinetic studies in rats.

Isomers 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8 trimethoxy flavone) (flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) (flavone B) have recently demonstrated differential antineoplastic activities against pancreatic cancer in vitro. These studies also indicated that these compounds target highly tumorigenic cells while sparing normal cells. The in vivo antitumor activities of these flavones have not been determined, and detection protocols for these compounds are needed to conduct pre-clinical assays following intravenous dosing. Here, we report methods developed using acetonitrile to extract two flavone isomers and corresponding internal standards, celecoxib and diclofenac, from rat plasma. Separation was achieved using a Shimadzu liquid chromatography system with a C18 column and mobile phase acetonitrile/water (60:40 and 70:30 for flavones A and B, respectively) containing 0.2% acetic acid and 0.05% triethylamine at a flow rate of 0.4mL/min and detection at 245nm. Calibration curves ranging from 250 to 2500ng/mL and 2500 to 100,000ng/mL for both flavones were linear (r(2)≥0.99) with the lower limits of quantification being 250ng/mL. Recovery of concentrations 250, 1000, 2500, 5000, and 100,000ng/mL ranged from 87 to 116% and 84 to 103% (n=3) for flavone A and B, respectively. Stability of both flavones after a freezing/thawing cycle yielded a mean peak ratio ≥0.92 when compared to freshly extracted samples. Intravenous administration of a 20mg/kg dose in rats yielded half-lives of 83.68±56.61 and 107.45±53.31min with clearance values of 12.99±13.78 and 80.79±35.06mL/min/kg for flavones A and B, respectively.

Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development.

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy. We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 and 177 mg/dl, respectively. We assessed neonatal physical development (pinnae unfolding, and eye opening); weight gain from postnatal day (PD) 3-65; and neurobehavioral maturation (pivoting, walking, cliff aversion, surface righting, vertical screen grasp, and rope balance) from PD3 to 17. We used a multiple linear regression model to determine the effects of dose, sex, day of treatment and birth in animals dosed during gastrulation or neurulation, relative to their vehicle controls. We found that ethanol exposure during both time points (GD7 and GD8) resulted in some delays of physical development and significant sensorimotor delays of pivoting, walking, and thick rope balance, as well as additional significant delays in cliff aversion and surface righting after GD8 treatment. We also found that treatment with the low ethanol dose more frequently affected neurobehavioral development of the surviving pups than treatment with the moderate ethanol dose, possibly due to a loss of severely affected offspring. Finally, mice born prematurely were delayed in their physical and sensorimotor development. Importantly, we showed that brief exposure to low dose ethanol, if administered during vulnerable periods of neuroanatomical development, results in significant neurobehavioral delays in neonatal mice. We thus expand concerns about alcohol consumption during the 3rd and 4th weeks of human pregnancy to include occasional light to moderate drinking.

Effects of formulation design on niacin therapeutics: mechanism of action, metabolism, and drug delivery.

Niacin is a highly effective, lipid regulating drug associated with a number of metabolically induced side effects such as prostaglandin (PG) mediated flushing and hepatic toxicity. In an attempt to reduce the development of these adverse effects, scientists have investigated differing methods of niacin delivery designed to control drug release and alter metabolism. However, despite successful formulation of various orally based capsule and tablet delivery systems, patient adherence to niacin therapy is still compromised by adverse events such as PG-induced flushing. While the primary advantage of orally dosed formulations is ease of use, alternative delivery options such as transdermal delivery or polymeric micro/nanoparticle encapsulation for oral administration have shown promise in niacin reformulation. However, the effectiveness of these alternative delivery options in reducing inimical effects of niacin and maintaining drug efficacy is still largely unknown and requires more in-depth investigation. In this paper, we present an overview of niacin applications, its metabolic pathways, and current drug delivery formulations. Focus is placed on oral immediate, sustained, and extended release niacin delivery as well as combined statin and/or prostaglandin antagonist niacin formulation. We also examine and discuss current findings involving transdermal niacin formulations and polymeric micro/nanoparticle encapsulated niacin delivery.

Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV) and 20 mg celecoxib without emulsifier (25.00±0.18 mV). Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively) and without (92.97±0.51 nm and 95.93±0.27%, respectively) emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01). Therefore, our results suggest the use of emulsifier free 5 mg celecoxib drug formulations containing 0.25% w/v didodecyldimethylammonium bromide for production of polymeric NPs that demonstrate enhanced zeta potential, small particle size, and high entrapment efficiency.

Nanoparticles in drug delivery: mechanism of action, formulation and clinical application towards reduction in drug-associated nephrotoxicity.

INTRODUCTION: Over the past few decades, nanoparticles (NPs) have gained immeasurable interest in the field of drug delivery. Various NP formulations have been disseminated in drug development in an attempt to increase efficacy, safety and tolerability of incorporated drugs. In this context, NP formulations that increase solubility, control release, and/or affect the in vivo disposition of drugs, were developed to improve the pharmacokinetic and pharmacodynamic properties of encapsulated drugs. AREAS COVERED: In this article, important properties related to NP function such as particle size, surface charge and shape are disseminated. Also, the current understanding of how NP characteristics affect particle uptake and targeted delivery is elucidated. Selected NP systems currently used in delivery of drugs in biological systems and their production methods are discussed as well. Emphasis is placed on current NP formulations that are shown to reduce drug-induced adverse renal complications. EXPERT OPINION: Formulation designs utilizing NP-encapsulated drugs offer alternative pharmacotherapy options with improved safety profiles for current and emerging drugs. NPs have been shown to increase the therapeutic index of several entrapped drugs mostly by decreasing drug localization and side effects on organs. Recent studies on NP-encapsulated chemotherapeutic and antibiotic medications show enhanced therapeutic outcomes by altering drug degradation, increasing systemic circulation and/or enhancing cell specific targeting. They may also reduce the distribution of encapsulated drugs into the kidneys and attenuate drug-associated adverse renal complications. The usefulness of NP formulation in reducing the nephrotoxicity of nonsteroidal anti-inflammatory drugs is an under explored territory that deserves more attention.