Development of next-generation macromolecular drugs based on the EPR effect: challenges and pitfalls.

Abstract:

INTRODUCTION:A major problem with conventional antitumor therapeutics is nonselective delivery of cytotoxic drugs to normal vital organs and tissues but little delivery to tumor tissues. AREAS COVERED:Here, the authors describe the tumor selective delivery of antitumor drugs by taking advantage of nano-sized drugs and the means to augment it further. Based on the enhanced permeability and retention (EPR) effect, the mechanism for more efficient universal tumor delivery using macromolecular drugs to cover wider tumor types than single molecular target is discussed. Unique properties of solid tumor vasculature in the tumor tissue are discussed, especially leakiness of the blood vessels and factors involved and impaired clearance of macromolecular drugs from the tumor interstitium via the lymphatic system. The criteria for such macromolecular drugs or nanomedicines for effective accumulation at tumor sites is commented on as well as the importance of long plasma retention time of such drugs and a need to release active principles from nanoparticles at target sites. Methods to augment the EPR effect and tumor delivery (2 - 3 times) and its application to photodynamic therapy are also discussed. EXPERT OPINION:Tumor selective delivery of antitumor drugs based on the EPR effect can be accomplished and augmented by modulating the tumor environment. This methodology is favorable not only for tumor therapy but also for tumor imaging.

journal_name

Expert Opin Drug Deliv

authors

Nakamura H,Fang J,Maeda H

doi

10.1517/17425247.2014.955011

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

53-64

issue

1

eissn

1742-5247

issn

1744-7593

journal_volume

12

pub_type

杂志文章,评审
  • Pulmonary delivery of anti-inflammatory agents.

    abstract:INTRODUCTION:Respiratory infections and diseases are accompanied by or exhibit inflammation. Recent advances in nanoparticle engineering technology, together with the increased knowledge of inflammatory pathophysiology, have ignited interest in the pulmonary delivery of anti-inflammatory agents (AIAs) to achieve local ...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2015.993968

    authors: Ali ME,McConville JT,Lamprecht A

    更新日期:2015-06-01 00:00:00

  • Drug delivery to macrophages: a review of nano-therapeutics targeted approach for inflammatory disorders and cancer.

    abstract:INTRODUCTION:Macrophages are involved in the normal defense of the body; however, the varying phenotypes of macrophages and imbalance in their ratio lead to the impairment of immune response initiating the production of inflammation. As the role of macrophages in immunological disorders and their surface receptors modu...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1080/17425247.2020.1783237

    authors: Mukhtar M,Ali H,Ahmed N,Munir R,Talib S,Khan AS,Ambrus R

    更新日期:2020-09-01 00:00:00

  • Epidermal delivery of protein and DNA vaccines.

    abstract::Targeting vaccines to the skin epidermis results in the activation of an immune inductive site that is rich in antigen-presenting cells. The superficial location of the skin makes it accessible to vaccine delivery. However, it is difficult to access the epidermis using needle and syringe delivery, and vaccine antigens...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2.2.227

    authors: Dean HJ

    更新日期:2005-03-01 00:00:00

  • New biomaterials for the sustained release of nitric oxide: past, present and future.

    abstract::Nitric oxide (NO), the 1992 'Molecule of the Year', is the focus of immense medical and scientific exploration. Interest in NO has grown exponentially since the initial and relatively recent discovery that NO is the long sought after endothelial relaxing factor. There is intense research that is continuing to expose t...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425240903196743

    authors: Friedman A,Friedman J

    更新日期:2009-10-01 00:00:00

  • Use of nanoscale delivery systems to maintain synergistic drug ratios in vivo.

    abstract:IMPORTANCE OF THE FIELD:Drug combinations have been the standard of care in the treatment of cancer for > 50 years. Typically, combination chemotherapy uses agents with non-overlapping toxicities which are escalated to their maximum tolerated dose. However, emerging evidence indicates that this approach may not be prov...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2010.538678

    authors: Dicko A,Mayer LD,Tardi PG

    更新日期:2010-12-01 00:00:00

  • The interaction of nanoparticles with plasma proteins and the consequent influence on nanoparticles behavior.

    abstract:INTRODUCTION:Plasma protein binding with nanoparticles (NPs) occurs immediately upon their introduction into a physiological environment and is affected by the characteristics of NPs, including their composition, size, shape and surface properties. According to their specific functions, adsorbed proteins can be divided...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2014.877442

    authors: Gao H,He Q

    更新日期:2014-03-01 00:00:00

  • Chitosan-based gastroretentive floating drug delivery technology: an updated review.

    abstract:INTRODUCTION:Gastroretentive floating drug delivery systems have emerged as efficient approaches for enhancing the bioavailability and controlled delivery of various therapeutic agents. Significant advancements exploiting chitosan have been made worldwide, in order to investigate these systems according to patient requ...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2012.673581

    authors: Pahwa R,Saini N,Kumar V,Kohli K

    更新日期:2012-05-01 00:00:00

  • Delivery of therapeutic RNA-cleaving oligodeoxyribonucleotides (deoxyribozymes): from cell culture studies to clinical trials.

    abstract:INTRODUCTION:Development of efficient in vivo delivery systems remains a major challenge en route to clinical application of antisense technology, including RNA-cleaving molecules such as deoxyribozymes (DNAzymes). The mechanisms of oligonucleotide uptake and trafficking are clearly dependent on cell type and the type ...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1080/17425247.2017.1266326

    authors: Fokina AA,Chelobanov BP,Fujii M,Stetsenko DA

    更新日期:2017-09-01 00:00:00

  • Advances in ocular drug delivery: emphasis on the posterior segment.

    abstract:INTRODUCTION:Recent advances in pharmacological therapies to treat ocular diseases such as glaucoma, age-related macular degeneration, diabetic macular edema and retinal vascular occlusions have greatly improved the prognosis for these diseases. Due to these advances in pharmacological therapy, there is a great deal of...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2014.935338

    authors: Kang-Mieler JJ,Osswald CR,Mieler WF

    更新日期:2014-10-01 00:00:00

  • New targeting strategies in drug therapy of inflammatory bowel disease: mechanistic approaches and opportunities.

    abstract:INTRODUCTION:Inflammatory bowel disease (IBD) is an exceptional scenario with regard to drug targeting, as oral administration has the potential to deliver the drug directly to the site(s) of action. Consequently, retention of the drug within the intestinal lumen and tissue, rather than systemic absorption, is frequent...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2013.800480

    authors: Wolk O,Epstein S,Ioffe-Dahan V,Ben-Shabat S,Dahan A

    更新日期:2013-09-01 00:00:00

  • Drug nanosuspensions: a ZIP tool between traditional and innovative pharmaceutical formulations.

    abstract:INTRODUCTION:A nanosuspension or nanocrystal suspension is a versatile formulation combining conventional and innovative features. It comprises 100% pure drug nanoparticles with sizes in the nano-scale range, generally stabilized by surfactants or polymers. Nanosuspensions are usually obtained in liquid media with bott...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2015.1043886

    authors: Leone F,Cavalli R

    更新日期:2015-01-01 00:00:00

  • Controlled release using mesoporous materials containing gate-like scaffoldings.

    abstract::The use of gated mesoporous silica solids as suitable systems for controlled-release protocols is reviewed. These materials are based on mesoporous silica supports that can be prepared with tailor-made pores of around 2 - 10 nm and that show a very large specific surface area (up to 1200 m(2)/g), thus having a large l...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425240902895980

    authors: Aznar E,Martínez-Máñez R,Sancenón F

    更新日期:2009-06-01 00:00:00

  • Physicochemical and physiological considerations for efficient nose-to-brain targeting.

    abstract:INTRODUCTION:Nasal drug delivery that exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain is being widely explored by pharmaceutical companies, for the delivery of challenging drugs. Low-molecular-weight and lipophilic drugs are effectively absorbed by the intranasal route for efficaci...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2012.636801

    authors: Bahadur S,Pathak K

    更新日期:2012-01-01 00:00:00

  • An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I.

    abstract:INTRODUCTION:Currently, hot melt extrusion (HME) is a promising technology in the pharmaceutical industry, as evidenced by its application to manufacture various FDA-approved commercial products in the market. HME is extensively researched for enhancing the solubility and bioavailability of poor water-soluble drugs, ta...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1080/17425247.2019.1609448

    authors: Kallakunta VR,Sarabu S,Bandari S,Tiwari R,Patil H,Repka MA

    更新日期:2019-05-01 00:00:00

  • Intranasal corticosteroids: the development of a drug delivery device for fluticasone furoate as a potential step toward improved compliance.

    abstract::Devices for the aqueous delivery of intranasal corticosteroids to patients with allergic rhinitis have been available since 1984, so there is a need for new devices to be developed to provide ease of use, efficacy and safety. A novel drug delivery system has been developed for fluticasone furoate (FF; GlaxoSmithKline)...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.4.6.689

    authors: Berger WE,Godfrey JW,Slater AL

    更新日期:2007-11-01 00:00:00

  • The biological routes of gene delivery mediated by lipid-based non-viral vectors.

    abstract::Cationic lipid/DNA complexes (lipoplexes) represent an attractive alternative to viral vectors for cell transfection in vitro and in vivo but still suffer from relatively low efficiency. Comprehension of the interactions between vectors and DNA as well as cellular pathways and mechanisms in DNA entry into cells and ul...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425240903287153

    authors: Duan Y,Zhang S,Wang B,Yang B,Zhi D

    更新日期:2009-12-01 00:00:00

  • Microbubble-mediated ultrasound drug-delivery and therapeutic monitoring.

    abstract:INTRODUCTION:Recent developments in ultrasound imaging and ultrasound contrast agents (UCAs) improved diagnostic confidence in echography and set into motion their combined use as a tool for drug delivery and therapeutic monitoring. Non-invasive, precise and targeted delivery of drug molecules to pathological tissues b...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1080/17425247.2017.1266328

    authors: Sennoga CA,Kanbar E,Auboire L,Dujardin PA,Fouan D,Escoffre JM,Bouakaz A

    更新日期:2017-09-01 00:00:00

  • Skin permeation behavior of elastic liposomes: role of formulation ingredients.

    abstract:INTRODUCTION:With the incorporation of edge activators into the lipid bilayer structure, elasticity properties are given to liposomes. Regardless of the debate over the precise permeation mechanism of elastic liposomes, these vesicles have been proven to enhance drug permeation into or through skin in most cases. AREA...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2013.779252

    authors: Chen J,Lu WL,Gu W,Lu SS,Chen ZP,Cai BC

    更新日期:2013-06-01 00:00:00

  • The microfabricated electrokinetic pump: a potential promising drug delivery technique.

    abstract::Directly delivering liquid using direct current power was a dream for 40 years. Now, the electrokinetic pump can accomplish it. This review reports recent developments in microfabricated electrokinetic pump technologies and their applications, and also discusses the electrophoresis pump and elctroosmotic pump, as well...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.4.2.119

    authors: Chen L,Choo J,Yan B

    更新日期:2007-03-01 00:00:00

  • A pen device for injection of recombinant human growth hormone: a European usability engineering study.

    abstract:OBJECTIVE:The Aluetta™ reusable pen device and instructions for use (IFU) for growth hormone (r-hGH; Saizen®, Merck KGaA, Darmstadt, Germany) administration were tested for Human-Factors Usability, to ensure it could be used safely and effectively by the intended users in the intended use environment. RESEARCH DESIGN ...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章

    doi:10.1080/17425247.2020.1774549

    authors: Cachemaille A,Warren SE,Moss S

    更新日期:2020-07-01 00:00:00

  • Bisphosphonate-modified biomaterials for drug delivery and bone tissue engineering.

    abstract:INTRODUCTION:Bisphosphonates (BPs) were introduced 45 years ago as anti-osteoporotic drugs and during the last decade have been utilized as bone-targeting groups in systemic treatment of bone diseases. Very recently, strategies of chemical immobilization of BPs in hydrogels and nanocomposites for bone tissue engineerin...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2015.1021679

    authors: Ossipov DA

    更新日期:2015-01-01 00:00:00

  • Preclinical models for pulmonary drug delivery.

    abstract:BACKGROUND:The lung comprises an interesting route of administration not only for topical drugs but also for systemically acting drugs. Over the last years, several models have been developed in order to study the efficacy and safety of pulmonary drug delivery. OBJECTIVE:This review describes relevant drug delivery mo...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425240903241788

    authors: Fernandes CA,Vanbever R

    更新日期:2009-11-01 00:00:00

  • An innovative corticosteroid/long-acting β2-agonist breath-triggered inhaler: facilitating lung delivery of fluticasone propionate/formoterol fumarate for the treatment of asthma.

    abstract::Introduction: Incorrect inhaler technique is one reason why the efficacies of inhaled asthma treatments in clinical trials and effectiveness in the real world differ. Inhaler technique is critical for drug delivery to the lungs; incorrect technique negatively impacts asthma control and long-term outcomes. Breath-trigg...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1080/17425247.2019.1689957

    authors: Usmani O,Roche N,Marshall J,Danagher H,Price D

    更新日期:2019-12-01 00:00:00

  • A meta-opinion: cannabinoids delivered to oral mucosa by a spray for systemic absorption are rather ingested into gastro-intestinal tract: the influences of fed / fasting states.

    abstract::Introduction: Sativex® spray is clinically utilized to deliver delta9-tetrahydrocannabinol and cannabidiol to oral mucosa for systemic absorption. We challenge the consensus that the mechanism of absorption following the oro-mucosal application occurs via the buccal tissue. Areas covered: Correctness of the consensus ...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1080/17425247.2019.1653852

    authors: Itin C,Domb AJ,Hoffman A

    更新日期:2019-10-01 00:00:00

  • Delivery methods for drugs used in the treatment of overactive bladder.

    abstract:INTRODUCTION:Overactive bladder affects a significant portion of the population and results in prescribing of numerous medications for its treatment. Traditional drug delivery systems used in therapy are associated with multiple commonly reported side effects. Adherence rates with use of these medications are low. It i...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2016.1130033

    authors: Scott K,Dmochowski RR,Padmanabhan P

    更新日期:2016-01-01 00:00:00

  • Microarrays and microneedle arrays for delivery of peptides, proteins, vaccines and other applications.

    abstract:INTRODUCTION:Peptide and protein microarray and microneedle array technology provides direct information on protein function and potential drug targets in drug discovery and delivery. Because of this unique ability, these arrays are well suited for protein profiling, drug target identification/validation and studies of...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2013.797405

    authors: Chandrasekhar S,Iyer LK,Panchal JP,Topp EM,Cannon JB,Ranade VV

    更新日期:2013-08-01 00:00:00

  • Harnessing CD47 mimicry to inhibit phagocytic clearance and enhance anti-tumor efficacy of nanoliposomal doxorubicin.

    abstract:BACKGROUND:We hypothesized if phagocytosis of liposomes by macrophages could be mitigated through incorporation of a CD47 mimicry peptide (Self peptide: SP) on the surface of liposomes. METHODS:Thin film hydration method followed by extrusion was used to prepare nanoliposomes, and Dox encapsulation in liposomes was do...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章

    doi:10.1080/17425247.2020.1772749

    authors: Gheibi Hayat SM,Jaafari MR,Hatamipour M,Jamialahmadi T,Sahebkar A

    更新日期:2020-07-01 00:00:00

  • Liposomes for targeted delivery of antithrombotic drugs.

    abstract:BACKGROUND:Targeted delivery of antithrombotic (thrombolytic) drugs is expected to increase their efficacy and decrease side effects, especially in the case of thrombolytic enzymes. Liposomes, phospholipid nanosized bubbles with a bilayered membrane structure, have drawn a lot of interest as pharmaceutical carriers for...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425240802497457

    authors: Elbayoumi TA,Torchilin VP

    更新日期:2008-11-01 00:00:00

  • Properties, characteristics and applications of microbubbles for sonothrombolysis.

    abstract:INTRODUCTION:Ultrasound enhancement of thrombolysis (sonothrombolysis) is further potentiated by administration of acoustically active microbubbles, which may be developed into powerful adjuvant therapies for thrombolytic treatment of occlusive conditions such as ischaemic stroke. AREAS COVERED:The role of microbubble...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章,评审

    doi:10.1517/17425247.2014.868434

    authors: de Saint Victor M,Crake C,Coussios CC,Stride E

    更新日期:2014-02-01 00:00:00

  • Combined strategy for suppressing breast carcinoma MCF-7 cell lines by loading simvastatin on alpha lipoic acid nanoparticles.

    abstract:BACKGROUND:Augmentation of simvastatin (SMV) cytotoxicity in breast carcinoma cell lines MCF-7, by: improvement of cellular uptake and loading on alpha lipoic acid (ALA). METHODS:In this study, SMV was loaded on ALA nanoparticles and characterized for surface morphology, SMV entrapment efficiency percent (%EE), zeta p...

    journal_title:Expert opinion on drug delivery

    pub_type: 杂志文章

    doi:10.1080/17425247.2016.1236788

    authors: Fahmy UA,Aljaeid BM

    更新日期:2016-12-01 00:00:00