New formulations of bupivacaine for the treatment of postoperative pain: liposomal bupivacaine and SABER-Bupivacaine

Introduction: Although generally considered both safe and effective, local anesthetics are often used in conjunction with opioids postoperatively in part because of the limited duration of drug action of local anesthetics. Much interest exists in extending the duration of local anesthetics’ effects, which may reduce the requirement for opioid pain medications that are frequently associated with side effects, including nausea and vomiting, pruritus and respiratory depression.

Areas covered: This article introduces liposomal bupivacaine and SABER®-Bupivacaine, two new formulations of bupivacaine that increase the duration of analgesia postoperatively through two novel slow-release technologies. The pharmacodynamics, pharmacokinetics, efficacy and safety of both preparations of bupivacaine are reviewed. An electronic database search conducted using the Cochrane Central Register of Controlled Trials and MEDLINE/PubMed with the following search terms: ‘bupivacaine,’ ‘liposomal bupivacaine’, ‘liposome bupivacaine’, ‘Exparel’, ‘SABER-Bupivacaine’, ‘SABER Bupivacaine’, and ‘SABER’ yielded 90 articles (no language or date of publication restrictions were imposed).

Expert opinion: Clinical trials involving liposomal bupivacaine and SABER-Bupivacaine indicate that both safely prolong analgesia, while decreasing opioid requirements when compared with placebo. However, additional clinical studies are necessary to better determine the efficacy and cost-effectiveness of these long-acting local anesthetic formulations.     

Micro and nanosystems for delivering local anesthetics

Introduction: One of the most common strategies for pain control during and after surgical procedures is the use of local anesthetics. Prolonged analgesia can be safely achieved with drug delivery systems suitably chosen for each local anesthetic agent.

Areas covered: This review considers drug delivery formulations of local anesthetics designed to prolong the anesthetic effect and decrease toxicity. The topics comprise the main drug delivery carrier systems (liposomes, biopolymers, and cyclodextrins) for infiltrative administration of local anesthetics. A chronological review of the literature is presented, including details of formulations as well as the advantages and pitfalls of each carrier system. The review also highlights pharmacokinetic data on such formulations, and gives an overview of the clinical studies published so far concerning pain control in medicine and dentistry.

Expert opinion: The design of novel drug delivery systems for local anesthetics must focus on how to achieve higher uploads of the anesthetic into the carrier, and how to sustain its release. This comprehensive review should be useful to provide the reader with the current state-of-art regarding drug delivery formulations for local anesthetics and their possible clinical applications.     

Public Perspectives of Using Social Media Data to Improve Adverse Drug Reaction Reporting: A Mixed-Methods Study

Introduction

Information on suspected adverse drug reactions (ADRs) voluntarily submitted by patients can be a valuable source of information for improving drug safety; however, public awareness of reporting mechanisms remains low. Whilst methods to automatically detect ADR mentions from social media posts using text mining techniques have been proposed to improve reporting rates, it is unclear how acceptable these would be to social media users.

Objective

The objective of this study was to explore public opinion about using automated methods to detect and report mentions of ADRs on social media to enhance pharmacovigilance efforts.

Methods

Users of the online health discussion forum HealthUnlocked participated in an online survey (N = 1359) about experiences with ADRs, knowledge of pharmacovigilance methods, and opinions about using automated data mining methods to detect and report ADRs. To further explore responses, five qualitative focus groups were conducted with 20 social media users with long-term health conditions.

Results

Participant responses indicated a low awareness of pharmacovigilance methods and ADR reporting. They showed a strong willingness to share health-related social media data about ADRs with researchers and regulators, but were cautious about automated text mining methods of detecting and reporting ADRs.

Conclusions

Social media users value public-facing pharmacovigilance schemes, even if they do not understand the current framework of pharmacovigilance within the UK. Ongoing engagement with users is essential to understand views, share knowledge and respect users’ privacy expectations to optimise future ADR reporting from online health communities.

     

Strategies for delivering local anesthetics to the skin: focus on liposomes,solid lipid nanoparticles,hydrogels and patches

Introduction: Dermal and transdermal drug delivery systems offer the possibility to control the release of the drug for an extended period of time. In particular, skin-delivery of local anesthetics (LA) is one of the most important strategies to increase the local drug concentration and to reduce systemic adverse reactions.

Areas covered: During the development phase of new formulations for skin-delivery of LA one should consider a set of desirable features such providing suitable adhesion, easy application/removal and also to be biocompatible, biodegradable and non-toxic. This review emphasizes the main strategies for skin-delivery of LA considering those features in relation to the composition of the delivery systems described. The topics highlight the relationships between physico-chemical studies and pharmaceutical applications for liposomes and solid lipid nanoparticles as well as the formulation and clinical applications for hydrogels and patches.

Expert opinion: The development of LA skin-delivery systems using hydrogels and different permeation enhancers, liposomes or lipid nanoparticles (as isolated carrier systems or as their dispersion in a gel-base) and patches have been explored as alternatives to commercial formulations, modifying the release rate of LA, increasing bioadhesive properties and reducing toxicity, resulting in an improved therapeutic efficacy. This review should provide to the reader a special emphasis on four delivery-systems, comprising the group of liposomes and lipid nanoparticles, hydrogels and patches technologies looking forward their application for skin anesthesia.     

Statin drug interactions and related adverse reactions

Introduction: Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, their possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment.

Areas covered: This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions and related adverse reactions.

Expert opinion: Avoiding drug–drug interactions and consequent adverse drug reactions is essential in order to optimize compliance, and thus improve the treatment of patients at high cardiovascular risk. The different pharmacokinetic profiles among statins should be carefully considered, in order to understand the possible spectrum of drug interactions. The growing trend toward earlier statin treatment for the prevention of cardiovascular disease means that physicians must anticipate future polypharmacy when their patients require additional medications for comorbid conditions.     

Selective TNF-α inhibitor-induced injection site reactions

Introduction: During the last decade, many new biological immune modulators entered the market as new therapeutic principles. TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenic mechanisms of various immune-mediated or inflammatory diseases. TNF-α blockers have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs.

Areas covered: Although generally well tolerated and safe, potential adverse events may be associated with TNF-α inhibitor treatment. The authors will briefly review the potential adverse drug reactions and the immunological mechanisms of injection site reactions (ISRs) in patients treated with etanercept and adalimumab.

Expert opinion: Patients treated with TNF-α inhibitors can develop ISR around the sites of injections. ‘Type IV delayed type reaction' or ‘recall ISRs'. Eosinophilic cellulitis or ‘Wells syndrome', ‘Type III' and ‘Type I' reactions are reported. Long-term studies are necessary to determine the durability of response and the real risk of ISRs with golimumab and certolizumab pegol. Further studies are also necessary to evaluate the immunogenicity of these drugs.     

Skin tolerability of transdermal patches

Introduction: Transdermal patch systems are an effective method of administering active ingredients through the skin, with considerable advantages over other drug delivery routes, for example, maintenance of constant plasma drug levels and avoidance of first-pass metabolism. However, repeated epicutaneous application may be associated with local skin reactions.

Areas covered: This review addresses current issues regarding the effective/safe use of transdermal patch systems, and provides a critical analysis of the addition of ‘skin-caring’ ingredients to patch systems. Effective use of transdermal systems includes choosing an appropriate body area for application, maintaining regular skin care regimens before application and not replacing a patch in the same area (rotation) within 7 days. Another strategy, developed in an attempt to improve the tolerability of transdermal systems, is the addition of assumed ‘skin-caring’ ingredients (e.g., Aloe Vera) to patch systems. However, at present there is neither proof nor clinical evidence of any benefit. On the contrary, plant-derived ingredients might be associated with allergenic potential.

Expert opinion: Transdermal systems are generally well tolerated; physicians must adequately inform patients of the most effective ways to use these formulations for maximum therapeutic benefit, while minimising local adverse events. Skin-caring agents, including Aloe Vera, cannot be recommended until well-controlled clinical trials with standardised extracts are available.     

UK addiction research 1994–2001: A profile of studies published in Addiction Abstracts

Introduction: In 2002 the National Treatment Agency for Substance Misuse commissioned a consultation exercise to help identify future research priorities. An overview of UK research published in the journal Addiction Abstracts contributed to this.

Method: Using a Microsoft Access database, two reviewers systematically profiled all 840 UK abstracts published between 1994 and 2001. The database included 72 fields for each abstract and a coding framework of predefined options.

Results: Fifty-seven percent (n?=?482) of the 840 abstracts reported studies involving licit substances, of which 65% discussed alcohol and 30% covered tobacco/nicotine. Sixty-three percent (n?=?530) covered illicit substances, a high proportion of which described non-specific drug use such as ‘general drug use’ (32%) or ‘injecting’ (16%), rather than individual substances. Heroin was the most common substance specified (8%). Few of the 840 abstracts focused upon subjects with predefined demographic characteristics: 8% detailed single gender studies; 2% reported an ethnic focus. Subgroup surveys were the most frequent research method adopted (32%); 15% described literature reviews, and 7% were ‘laboratory experimental’. Two percent of studies were identified as randomized controlled trials.

Conclusion: Our research presents a useful profile of published UK research and provides a focus for reflection and debate on future priorities.     

The clinical significance of the size of low-density-lipoproteins and the modulation of subclasses by fibrates

ABSTRACT

Background: Beyond total low-density-lipoproteins (LDL) levels, increasing evidence suggests that the ‘quality’ of LDL exerts a great influence on the cardiovascular risk. Several studies have also shown that the therapeutic modulation of LDL size is of benefit in reducing the risk of cardiovascular events. Hypolipidaemic treatment is able to alter LDL subclass distribution but strong variations have been noticed among different agents. Fibrates have a major impact on triglyceride metabolism and in modulating LDL size and subclasses, but variations exist among the different molecules.

Methodology: A literature search (by Medline and Scopus) was performed using the following headings: ‘small dense LDL’, ‘LDL size’, ‘LDL subfractions’, ‘LDL subclasses’, ‘LDL distribution’ and ‘fenofibrate’, ‘bezafibrate’, ‘ciprofibrate’ and ‘gemfibrozil’ up to 20 January 2007. The authors also manually reviewed the references of selected articles for any pertinent material.

Results: Analysis of all published studies revealed that treatment with fenofibrate, ciprofibrate, bezafibrate and gemfibrozil is usually beneficial, and fenofibrate may be more efficacious than the other molecules. This is supported by using all the available techniques in subjects with a very wide range of lipid alterations.

Conclusion: Among the different agents, fenofibrate has been found to be particularly effective in modulating LDL size and subclasses in patients at higher cardiovascular risk, such as those with type 2 diabetes or the metabolic syndrome.     

On the clinical evidence leading to tetrazepam withdrawal

Introduction: In July 2013, the European Medicines Agency suspended the marketing authorizations of tetrazepam across the European Union. Herein, we examine the various kinds of adverse drug reactions (ADRs) reported to be associated with tetrazepam.

Areas covered: We undertook a two-sided systematic approach. First, we conducted a search in Medline for all studies that have published about tetrazepam ADRs in peer-reviewed journals. Second, we collected tetrazepam ADRs from pharmacovigilance system databases. Our study reveals discrepancies in the information provided by these two different sources, both in the number of cases reported as well as in the kind of reported ADRs. Whereas cutaneous alterations are the only ADRs reported in peer-reviewed journals, pharmacovigilance system databases include others (hepatobiliary, neurological and psychiatric).

Expert opinion: We noted the lack of randomized controlled clinical trials evaluating tetrazepam efficiency and safety. We failed to find a turning point in the amount of ADRs reported following tetrazepam withdrawal to underpin the validity of the withdrawal. We stress the importance of a better communication of knowledge in scientific literature, pharmacovigilance agencies, and from doctors to prevent marketed usage of drugs with well-established side effects during long periods.     

Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

ABSTRACT

Objective: To evaluate the safety and tolerability of prolonged-release nicotinic acid (Niaspan) added to statin therapy in patients at increased cardiovascular risk.

Methods: This was a 6-month, prospective, observa­tional, multicentre, open-label evaluation of prolonged-release nicotinic acid (maximum dose 2000?mg/day) in statin-treated patients with cardiovascular disease and/or type 2 diabetes. The primary endpoint was the safety and tolerability of prolonged-release nicotinic acid, with special regard to treatment-related adverse drug reactions (ADRs). Secondary endpoints were changes in lipids and 10-year cardiovascular risk (Prospective Cardiovascular Münster (PROCAM) score).

Results: The study population included 1053 patients: 50% had hypertension, diabetes and/or metabolic syndrome (National Cholesterol Education Program/Adult Treatment Panel III criteria) and 80% had cardiovascular disease. Flushing (mostly mild or moderate) occurred in 430 patients (40.8%). Other ADRs occurred in 125 patients (12.5%), most commonly pruritus (2.7%), gastro­intestinal symptoms (3.8%) and nervous system-related complaints (3.8%). Serious ADRs were uncommon (0.6%). All patients recovered completely from these ADRs after treatment discontinuation. In total, 11.1% of the patients discontinued study medication for flushing and 8.4% for other ADRs. There was no evidence of hepatotoxicity or myopathy. New-onset hyperglycaemia was negligible. Overall tolerability of prolonged-release nicotinic acid treatment (n = 734 patients at closeout) was ‘very good’ in 130 (17.7%), ‘good’ in 262 (35.7%), and ‘acceptable’ in 144 (19.6%) patients. High-density lipoprotein (HDL) cholesterol increased by 23%, triglycerides decreased by 15% and LDL-C decreased by 4%.

Conclusions: Prolonged-release nicotinic acid was safe and generally well tolerated and effective in combination with statin therapy in patients at high risk of cardio­vascular events, with a side-effect profile consistent with previous clinical experience.     

Non-sedating antihistamines in the treatment of chronic idiopathic urticaria using patient-reported outcomes

ABSTRACT

Background: Chronic idiopathic urticaria (CIU) greatly impairs quality of life (QoL). Thus, patient-reported outcome (PRO) measures, using validated scoring instruments, are probably the most accurate tools available for assessing the efficacy of medications that treat CIU, such as second-generation antihistamines.

Research methods: A structured search of the MEDLINE database was conducted to identify English-language papers published between 1 January 1991 and 30 September 2007 on the treatment of CIU with the second-generation antihistamines cetirizine, desloratadine, fexofenadine, and levocetirizine, and their effects on patient-reported QoL. We used the following search terms alone or in combination: ‘chronic idiopathic urticaria’; ‘pruritus’; ‘wheals’; ‘hives’; ‘second-generation antihistamines’; ‘cetirizine’; ‘desloratadine’; ‘fexofenadine’; ‘levocetirizine’; and ‘quality of life’.

Scope: We evaluated the effects of second-generation antihistamines on the QoL of subjects with CIU using desloratadine as a treatment model. Desloratadine was selected because it is the most frequently assessed non-sedating second-generation antihistamine in QoL studies in patients with CIU.

Findings: Desloratadine 5?mg QD improved QoL in numerous PRO studies. Treatment with desloratadine significantly (p?<?0.05) lowered (better) scores in three studies (n?=?364) that used validated dermatology-specific scoring instruments. Three 6-week double-blind, placebo-controlled trials (n?=?553) found that desloratadine significantly (p?<?0.05) improved patient-reported pruritus, sleep disruption, and interference with daily activities. Desloratadine was associated with a low incidence of adverse events and an overall tolerability profile similar to placebo.

Limitations: Limitations in this review include divergence in search practices that may lead to omission of relevant research, unintentional error in data transfer, inconsistency in quality of selected papers, and potential publication bias against papers that report results from small studies.

Conclusions: The favorable impact of second-generation antihistamines on the QoL of patients with CIU was demonstrated using desloratadine, the most frequently investigated drug in this field, as a treatment model.     

基于上市许可持有人的药品不良反应主动监测模式的构建与评估研究

目的：探讨药品上市许可持有人（Marketing Authorization Holder,MAH）的药品不良反应主动监测创新模式的构建及其效果评估,为落实MAH药物警戒主体责任提供实证参考。方法：首先针对MAH药物警戒的现存挑战,基于中国医院药物警戒系统（Chinese Hospital Pharmacovigilance System,CHPS）设计MAH针对药品不良反应的主动监测模式,包括不良反应的监测、识别、评估及控制;再以注射用卡瑞利珠单抗为例分析主动监测效果。结果与结论：从MAH视角,构建基于CHPS整合循证证据和真实世界数据开展ADR主动监测的创新模式,包括运行模式、数据挖掘及模型构建。该主动监测模式被成功应用到以卡瑞利珠单抗为例的临床实践中,取到良好的效果。该研究成果不仅能帮助MAH开展药品监测工作,落实药品全生命周期主体责任,还能丰富药物警戒的内涵,为促进药物警戒发展和合理用药提供具有可操作性的实证参考。     

Statins in patients with chronic kidney disease: why,who and when?

Importance of the field: Patients with end-stage renal disease are at high risk of developing cardiovascular disease, which is characterized by early onset and rapid progression of atherosclerosis. Some analyses of large clinical trials have revealed that statins might reduce all-cause mortality and cardiovascular (CV) events in patients with chronic kidney disease (CKD). Preliminary studies have also suggested that they can reduce contrast-induced nephropathy (CIN) and the rate of loss of kidney function. However, the results concerning the efficacy and safety of statin therapy in patients with CKD, especially in those on renal replacement therapy, are still controversial.

Areas covered in this review: This review contains data on the atherosclerotic risk in patients with CKD; the role of statins in the reduction of CV risk in patients with CKD; the role of CIN; the effects of statins on retarding the progression of CKD; and the efficacy of statin therapy in CKD, dialysis and renal-transplant patients. We searched using the electronic databases [MEDLINE (1966 – June 2010), EMBASE and SCOPUS (1965 – June 2010), DARE (1966 – June 2010)]. Additionally, abstracts from national and international cardiovascular meetings were studied. Where necessary, the relevant authors of these studies were contacted to obtain further data. The main data search terms were: ‘statin/statins’, ‘dialysis’, ‘dyslipidemia’, ‘hemodialysis’, ‘kidney disease’, ‘microalbuminuria’, ‘clinical trials’, and ‘renal impairment’.

What the reader will gain: Readers will be acquainted with results of clinical trials, including the most recent ones (e.g., PLANETE I and II), and will be able to draw their own conclusions concerning the use of statins in CKD patients on the basis of the results of the studies presented and to compare them with the authors' suggestions presented in this review.

Take home message: Although the results of trials are conflicting, it is suggested that the benefits of statin use outweigh the drawbacks in patients with early-stage CKD, when the benefits can be effectively predicted. However, available large randomized clinical trials suggest a lack of efficacy in patients on renal replacement therapy.     

Assessing the Impact on Health of Pharmacovigilance Activities: Example of Four Safety Signals

Introduction

The impact of pharmacovigilance activities on public health remains under-investigated, and measuring the impact on health of pharmacovigilance activities for a specific safety signal is challenging.

Objective

To gain more insight into the methodological challenges and the data required, we assessed the impact of pharmacovigilance on public health for four identified product-specific safety signals using publicly available data in the Netherlands. The assessment was on the impact of the intertwined and complementary steps of the pharmacovigilance pathways.

Methods

The impact of pharmacovigilance on public health was assessed using the assessment support tool and ‘open data’ from the Netherlands for four different types of pharmacovigilance safety signals: (1) off-label use of cyproterone acetate/ethinyloestradiol (CPA/EE) and thrombotic risk after pharmacovigilance measures after 2014; (2) pergolide and the risk of cardiac valvulopathy after pharmacovigilance activities in 2003; (3) proton pump inhibitors and the risk of hypomagnesaemia after pharmacovigilance activities in 2011; (4) rosiglitazone withdrawal from the market because of cardiovascular effects in 2010.

Results

For the signals on CPA/EE and pergolide, a crude estimation of the impact could be made with varying degrees of assumptions based on the risk described in the literature and utilisation data.

Conclusion

This article highlights the methodological challenges and the data required to assess the impact of product-specific safety signals. A structured assessment support tool can be used as a guide for the necessary data elements and steps needed for the measurement or estimation of impact of pharmacovigilance activities on public health, provided that the appropriate data are available.

     

Pitolisant for treating patients with narcolepsy

ABSTRACT

Introduction: Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. Pitolisant is a first-in-class drug acting on histamine 3 receptors and indicated for the treatment of narcolepsy. This article aims to review pitolisant.

Areas covered: In this paper the chemical properties, mechanism of action, pharmacokinetics, clinical efficacy and safety of pitolisant was introduced, and the development course of drugs for treating narcolepsy is also briefly described. We performed a systematic review of the literature using PubMed and the following keywords were used: ‘pitolisant’ and ‘narcolepsy’, ‘cataplexy’ and ‘excessive daytime sleepiness’ and ‘histamine 3 receptor’.

Expert opinion: Pitolisant is a histamine 3 receptor antagonist/inverse agonist. It can activate histamine release in the brain and enhances wakefulness. Clinical studies showed that pitolisant significantly decreased excessive daytime sleepiness and cataplexy rate versus placebo. Pitolisant was well tolerated, common adverse reactions were headache, insomnia, nausea, and anxiety.     

Drug interactions with new oral anticoagulants in elderly patients

Introduction: This review attempts to summarise what is known about Drug-drug interactions (DDIs) of the new oral anticoagulants (NOACs) in elderly patients. The literature was searched for: ‘CYP3A4’, ‘CYP2C9’, ‘P-glycoprotein’, ‘acetylsalicylic-acid’, ‘non-steroidal anti-inflammatory’, ‘clopidogrel’, ‘ticagrelor’, ‘prasugrel’ and ‘dabigatran’, ‘rivaroxaban’, ‘edoxaban’, or ‘apixaban’. ‘Elderly’ was defined as ≥75 years.

Areas covered: Publications about DDIs of NOACs were found for 35% of 140 potentially interacting drugs. Reports about DDIs of cardiovascular drugs, were most frequent, followed by anti-infective and nervous system drugs. Reports about elderly were found for only 47 patients. DDIs were reported most frequently in association with dabigatran. Dabigatran is the only NOAC interacting with proton-pump-inhibitors.

Expert commentary: Dabigatran was the first NOAC approved, so it is not possible to determine whether the higher number of reports about DDIs with dabigatran compared with other NOACs is due to a higher rate of DDIs or to the length of time during which this drug has been in use. Most of the data is derived from subgroup-analyses of trials, sponsored by NOAC manufacturers, consequently there is a lack of independent data. Because of the scarcity of data, the clinical relevance of DDIs of NOACs is uncertain at present, especially in elderly patients.     

Impact of United States Food and Drug Administration's boxed warnings on adverse drug reactions reporting rates and risk mitigation for multiple myeloma drugs

Purpose: To determine the relationship between boxed warnings issuance by the US Food and Drug Administration (FDA) and the proportional reporting rates of the associated adverse drug reactions (ADRs) to the FDA's Adverse Event Reporting System (FAERS) for multiple myeloma (MM) drugs.

Methods: We compiled a list of all FDA approved MM drugs and identified their associated ADR boxed warnings, through FDA's website and physician desk reference. Drugs that were issued boxed warnings after their market launch were included in the analysis, i.e., melphalan, thalidomide, vincristine, carmustine and doxorubicin. For each drug/ADR boxed warning combination, we retrieved all reported cases from the FAERS and calculated their Empiric Bayes Geometric Means (EBGMs), in pre- and post-boxed warning periods. Chi-square tests were performed to compare serious adverse drug events before and after boxed warnings for all drug/ADR combinations.

Results: A total of 10 drug/ADR boxed warning combinations were identified, of which EBGM signals increased for six combinations after a boxed warning was issued. Reports of serious adverse drug events also increased significantly (p < 0.05).

Conclusion: Boxed warnings were associated with increased FAERS reporting, indicating increased awareness of ADRs for MM drugs. Proactive pharmacovigilance programs, such as the FDA's Mini-Sentinel Project, may improve timeliness of detection of rare ADRs.     

‘Smart’ nanoparticles as drug delivery systems for applications in tumor therapy

Introduction: In the therapy of clinical diseases such as cancer, it is important to deliver drugs directly to tumor sites in order to maximize local drug concentration and reduce side effects. This objective may be realized by using ‘smart’ nanoparticles (NPs) as drug delivery systems, because they enable dramatic conformational changes in response to specific physical/chemical stimuli from the diseased cells for targeted and controlled drug release.

Areas covered: In this review, we first briefly summarize the characteristics of ‘smart’ NPs as drug delivery systems in medical therapy, and then discuss their targeting transport, transmembrane and endosomal escape behaviors. Lastly, we focus on the applications of ‘smart’ NPs as drug delivery systems for tumor therapy.

Expert opinion: Biodegradable ‘smart’ NPs have the potential to achieve maximum efficacy and drug availability at the desired sites, and reduce the harmful side effects for healthy tissues in tumor therapy. It is necessary to select appropriate NPs and modify their characteristics according to treatment strategies of tumor therapy.