Expert Opinion on Drug Delivery

Description

Impact factor 4.87

  • 5-year impact
    5.13
  • Cited half-life
    3.70
  • Immediacy index
    0.50
  • Eigenfactor
    0.01
  • Article influence
    1.23
  • ISSN
    1744-7593

Publications in this journal

  • Richard F Pollock, Anne-Marie Kappelgaard, Lisa Seitz
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    ABSTRACT: Objective: Human growth hormone (hGH) delivery systems differ in the size of the dose increments that can be set by the patient, affecting proximity to the target (i.e., prescribed) dose which can be attained. We investigated differences in dosing increment granularity in NordiFlex®, FlexPro®, NordiPen® (all multiple dose devices) and MiniQuick® (single dose) delivery systems. Methods: A simulation model was developed to project hGH dosing in pediatric patients with growth hormone deficiency, small for gestational age or Turner syndrome, calculating the nearest dose above the target dose administrable by each device in typical EU and US cohorts and projecting the excess dose (hGH wastage) over 1 year of typical use. Results: The device with the smallest dosing increment (FlexPro 5 mg; 0.025 mg dosing increment) was projected to administer doses < 1% above the target across all indications. MiniQuick (0.2 mg dosing increment) was projected to deliver between 5 and 6% above the target dose. None of the sensitivity analyses changed the conclusion that larger dosing increments result in more hGH wastage. Conclusions: In addition to increasing dosing accuracy, finer dosing increments may result in reductions in unnecessary hGH usage, which may in turn result in reductions in the cost of hGH treatment borne by the health-care payer.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: Cancer stem cells (CSCs) play an important role in the development of drug resistance, metastasis and recurrence. Current conventional therapies do not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer cells have entered a new era of treatment, where specific targeting to CSCs may offer superior outcomes to efficient cancer therapies. Areas covered: This review discusses the involvement of CSCs in tumor progression and relevant mechanisms associated with CSCs resistance to conventional chemo- and radio-therapies. It highlights CSCs-targeted strategies that are either under evaluation or could be explored in the near future, with a focus on various nanocarrier-based delivery systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are presented in a cancer-specific way to provide a current perspective on anti-CSCs therapeutics. Expert opinion: The field of CSCs-targeted therapeutics is still emerging with a few small molecules and macromolecules currently proving efficacy in clinical trials. However considering the complexities of CSCs and existing delivery difficulties in conventional anticancer therapies, CSC-specific delivery systems would face tremendous technical and clinical challenges. Nanocarrier-based approaches have demonstrated significant potential in specific drug delivery and targeting; their success in CSCs-targeted drug delivery would not only significantly enhance anticancer treatment but also address current difficulties associated with cancer resistance, metastasis and recurrence. Read More: http://informahealthcare.com/doi/abs/10.1517/17425247.2015.998648
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: Since thiolated polymers – known as thiomers – have entered the pharmaceutical arena in the late 1990s, more and more academic and industrial research groups have started to work with these promising polymeric excipients. Meanwhile, various thiomers are the subject of clinical trials and the first product based on thiolated chitosan will reach the market in 2015. Due to the formation of disulfide bonds with mercaptopyridine substructures, thiol groups of thiomers are on the one hand more reactive and on the other hand are protected toward oxidation. These so-called preactivated thiomers representing the second generation of thiomers are subject of this review.Areas covered: Within this review, preactivated thiomers are classified and their mode of action is described. Furthermore, different synthetic pathways, purification and chemical characterization methods of preactivated thiomers are explained. Their properties including mucoadhesive, permeation-enhancing, efflux pump inhibitory and in situ gelling properties are described. In addition, various formulations based on preactivated thiomers are introduced.Expert opinion: The first-generation thiomers have already shown great potential resulting in various product developments. Preactivated thiomers – representing the second generation of thiomers – offer the additional advantage of even comparatively more reactive sulfhydryl ligands and of stability toward oxidation. According to this, they are promising novel polymeric excipients for various applications.
    Expert Opinion on Drug Delivery 01/2015;
  • Mahdi Karimi, Navid Solati, Mohammad Amiri, Hamed Mirshekari, Elmira Mohamed, Mahdiar Taheri, Mahshid Hashemkhani, Ahad Saeidi, Mehrdad Asghari Estiar, Parnian Kiani, Amir Ghasemi, Seyed Masoud Moosavi Basri, Amir R Aref, Michael R Hamblin
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    ABSTRACT: Introduction: It is 23 years since carbon allotrope known as carbon nanotubes (CNT) was discovered by Iijima, who described them as "rolled graphite sheets inserted into each other". Since then, CNTs have been studied in nanoelectronic devices. However, CNTs also possess the versatility to act as drug- and gene-delivery vehicles. Areas covered: This review covers the synthesis, purification and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor deposition are the principle synthesis methods. Non-covalent functionalization relies on attachment of biomolecules by coating the CNT with surfactants, synthetic polymers and biopolymers. Covalent functionalization often involves the initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3-dipolar cycloaddition or reductive alkylation. The aim is to produce functional groups to attach the active cargo. Expert opinion: In this review, the feasibility of CNT being used as a drug-delivery vehicle is explored. The molecular composition of CNT is extremely hydrophobic and highly aggregation-prone. Therefore, most of the efforts towards drug delivery has centered on chemical functionalization, which is usually divided in two categories; non-covalent and covalent. The biomedical applications of CNT are growing apace, and new drug-delivery technologies play a major role in these efforts.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: Apart from statins, anti-platelet agents and invasive procedures, the anti-atherosclerotic medical weaponry for coronary heart disease (CHD) is scarce and only partially protects CHD patients from major adverse cardiac events. Areas covered: Several novel non-invasive strategies are being developed to widen the therapeutic options. Among them, drug delivery tools were tested in vivo encompassing liposomes, micelles, polymeric, metallic and lipid nanoparticles used as carriers of statins, corticosteroids, a bisphosphonate, a glitazone, anti-cancer agents, a mycotoxin, a calcium channel blocker and a compound of traditional Chinese medicine. All preparations improved parameters related to atherosclerotic lesions induced in rabbits, rats and mice and reduced neointima formation in experiments aiming to prevent post-stenting restenosis. In subjects submitted to percutaneous coronary intervention, nanoparticle formulations of paclitaxel and alendronate showed safety but are still not conclusive regarding in-stent late loss. The experience of our group in atherosclerotic rabbits treated with non-protein lipid nanoparticles associated with anti-cancer drugs such as paclitaxel, etoposide and methotrexate is summarized, and preliminary safety data in CHD patients are anticipated. Expert opinion: Taken together, these studies show that non-invasive drug-delivery systems may become promising tools to rescue CHD patients from the risks of severe and life-threatening lesions that should be more energetically treated.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: Ample research has been done to study the role of oxidative stress due to the generation of excess reactive species in initiation and progression of diabetic complications. A positive result has been indicated hypothesizing that abating this oxidative stress can prove to be an alternate strategy in therapy apart from oral antidiabetic drugs. But these dietary antioxidants are less efficient because of poor solubility, permeability, instability on storage, gastrointestinal degradation and first-pass metabolism.Areas covered: This review gives a brief insight into the molecular mechanism of oxidative stress in development of diabetic complications. Major hurdles limiting the translation of antioxidants to clinical area are also discussed. Various delivery approaches including both conventional and novel drug delivery systems explored so far for combating these challenges in antioxidant delivery are also explored. Mitochondrial targeting of such molecules is also briefly discussed.Expert opinion: A thorough study of clinical efficacy and safety of antioxidants on long-term use judging its clinical applicability is required. The clinical success of antioxidants as a therapeutic strategy involves a combination of effective design of drug delivery carrier that are in turn related to their degradation profile, possibility of cellular uptake at defined site of action and so on and clinical and preclinical trials that will provide a base for the design of dose and administration regimen.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: An important factor responsible for suboptimal treatment in patients with obstructive airway diseases, which is often overlooked, is running out of medication. Addition of a dose counter to a pressurized metered-dose inhaler (pMDI) allows the patient to reliably track number of actuations, identify when the label claim number of actuations has been reached, and when a new inhaler needs to be purchased. Areas covered: This article discusses the conventional methods for tracking doses in pMDIs, rationale of using dose counters, published evidence of studies, including performance and patient satisfaction with the use of pMDIs with dose counter. A section on the FDA guidance on dose counters and on Cipla's dose counters is also included. Expert opinion: It has been several years since the US FDA guidance on integration of dose-counting mechanisms into pMDIs and some time since pMDIs with dose counters have been available (albeit not with all pMDIs); but their importance has not been fully realized. This can be due to factors such as lack of adequate understanding about dose tracking, limited pMDIs being available with integrated dose counters and absence of a clear consolidation of the need, advantages, guidelines, types and characteristics of dose counters in published articles.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: Cell encapsulation technology has improved enormously since it was proposed 50 years ago. The advantages offered over other alternative systems, such as the prevention of repetitive drug administration, have triggered the use of this technology in multiple therapeutic applications. Areas covered: In this article, improvements in cell encapsulation technology and strategies to overcome the drawbacks that prevent its use in the clinic have been summarized and discussed. Different studies and clinical trials that have been performed in several therapeutic applications have also been described. Expert opinion: The authors believe that the future translation of this technology from bench to bedside requires the optimization of diverse aspects: i) biosafety, controlling and monitoring cell viability; ii) biocompatibility, reducing pericapsular fibrotic growth and hypoxia suffered by the graft; iii) control over drug delivery; iv) and the final scale up. On the other hand, an area that deserves more attention is the cryopreservation of encapsulated cells as this will facilitate the arrival of these biosystems to the clinic.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: Thirty percent of top marketed drugs in the USA and 70% of all new drug candidates are lipophilic and exhibit poor water solubility. With such physicochemical properties, the oral bioavailability of these compounds lacks dose proportionality, is very limited and extremely erratic. Different lipid-based formulations have been explored in the past few decades to improve the oral delivery of such compounds. In recent years, the most popular approach is their incorporation into self-emulsifying drug delivery systems (SEDDS), with particular emphasis on self-nano-emulsifying drug delivery systems (SNEDDS). Areas covered: This review offers an updated overview of SNEDDS application from the biopharmaceutical point of view. The focus of this review deals with the potential of SNEDDS utilization to overcome absorption barriers following oral administration of lipophilic drugs. This includes a comprehensive description of the primary mechanisms by which lipids and lipophilic excipients, used to formulate SNEDDS, could affect drug absorption, bioavailability and disposition following oral administration. Expert opinion: The utilization of SNEDDS to augment the oral bioavailability of poorly water-soluble drugs goes beyond improvement in drug’s solubility, as was initially presumed. In fact, SNEDDS have a potential to increase oral bioavailability by multi-concerted mechanisms such as reduced intra-enterocyte metabolism by CYP P450 enzymes, reduced P-glycoprotein (P-gp) efflux activity and hepatic first-pass metabolism bypass via lymphatic absorption. This unique biopharmaceutical point of view, presented in this review, contributes to the understanding of proper drug candidate selection and of the approach in SNEDDS formulation design.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: The pulmonary route is not invasive and can be used to target drugs directly to the lungs, limiting the exposure of secondary organs. It is, thus, an attractive alternative to the intravenous route, for the delivery of mAbs, which display limited transfer from blood into the lungs. Areas covered: This review provides an overview of the pharmacological properties of antibody-based treatments, describes those for respiratory diseases and discusses preclinical/clinical results of aerosolized antibody-based therapeutics. The advantages and limitations of aerosol devices and the formulation for the administration of aerosolized mAbs are also detailed. Expert opinion: Overall, the inhalation of mAbs for therapeutic purposes is both appropriate and feasible. The size and structure of the biotherapeutic molecule are important properties to be taken into account when trying to achieve long-term retention. Mesh nebulizers currently appear to be the most appropriate devices for the safe delivery of large amounts of active mAb into the lungs. mAbs should be formulated so as to prevent their degradation and possible immunogenicity. General guidelines can be given for mAb aerosolization, but the formulation and device combination should be adapted for each therapeutic and clinical application.
    Expert Opinion on Drug Delivery 01/2015;
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    ABSTRACT: Introduction: Delivery of therapeutic insulin via the pulmonary route has been the most investigated non-invasive alternative to the commonly used subcutaneous (SC) route for diabetes management. Despite discontinuation of the first inhalable insulin, Exubera®, due to suboptimal market acceptance, development of orally inhaled insulin delivery systems has been galvanized by the recent approval of Afrezza® and several others awaiting approval. Areas covered: The scope of this review article includes the prospects for and the challenges faced in developing inhaled insulin delivery systems; discussion of orally inhaled therapeutic insulin delivery systems that were discontinued, recently approved or are currently under active investigation; and formulation approaches that have the potential to deliver insulin via the pulmonary route. Expert opinion: The pulmonary route is the most advantageous route for non-invasive insulin delivery. Inhalable insulin therapeutics have the potential to be successful, provided that the formulations can be made with modified release patterns to substitute for both prandial and basal insulin injections, the delivery devices are convenient and easy to use, and the long-term safety of inhaled insulin is documented through extensive studies.
    Expert Opinion on Drug Delivery 12/2014;
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    ABSTRACT: Introduction: The number of pulmonary diseases that are effectively treated by aerosolized medicine continues to grow. Areas covered: These diseases include chronic obstructive pulmonary disease (COPD), lung inflammatory diseases (e.g., asthma) and pulmonary infections. Dry powder inhalers (DPIs) exhibit many unique advantages that have contributed to the incredible growth in the number of DPI pharmaceutical products. To improve the performance, there are a relatively large number of DPI devices available for different inhalable powder formulations. The relationship between formulation and inhaler device features on performance of the drug-device combination product is critical. Aerosol medicine products are drug-device combination products. Device design and compatibility with the formulation are key drug-device combination product aspects in delivering drugs to the lungs as inhaled powders. In addition to discussing pulmonary diseases, this review discusses DPI devices, respirable powder formulation and their interactions in the context of currently marketed DPI products used in the treatment of COPD, asthma and pulmonary infections. Expert opinion: There is a growing line of product options available for patients in choosing inhalers for treatment of respiratory diseases. Looking ahead, combining nanotechnology with optimized DPI formulation and enhancing device design presents a promising future for DPI development.
    Expert Opinion on Drug Delivery 11/2014;
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    ABSTRACT: Introduction: Transdermal drug delivery offers a number of advantages for the patient, not only due to its non-invasive and convenient nature, but also due to factors such as avoidance of first-pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedles (MNs) can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below. Areas covered: MNs have been extensively investigated for drug and vaccine delivery. The different types of MN arrays and their delivery capabilities are discussed in terms of drugs, including biopharmaceutics and vaccines. Patient usage and effects on the skin are also considered. Expert opinion: MN research and development is now at the stage where commercialisation is a viable possibility. There are a number of long-term safety questions relating to patient usage which will need to be addressed moving forward. Regulatory guidance is awaited to direct the scale-up of the manufacturing process alongside provision of clearer patient instruction for safe and effective use of MN devices.
    Expert Opinion on Drug Delivery 07/2014;
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    ABSTRACT: Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application. Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo. Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat. Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 - ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension. Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.
    Expert Opinion on Drug Delivery 06/2014;
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    ABSTRACT: Introduction: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease. Areas covered: The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative dry powder inhaler (DPI), NEXThaler®. The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs. Expert opinion: The data show that the NEXThaler® DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler® DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and supports the broad utility of the NEXThaler® DPI in patients with asthma. Overall, all the effectiveness, efficiency and satisfaction outcomes demonstrate the NEXThaler® DPI is easy to use.
    Expert Opinion on Drug Delivery 06/2014;
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    ABSTRACT: Micromotors and nanomotors are an emerging research field that aims at achieving locomotion on the microscale for a variety of applications such as drug delivery, single cell manipulation, microsensors and lab-on-a-chip devices, just to point out a few. The enthusiastic development of hybrid micromotors harnessing biological power sources for physiologically compatible nano/microdevices has recently brought a lot of attention to the international research community that is looking for a solution for the actuation and locomotion on the microscale. This article describes the potential of sperm-driven micro-bio-robots in the biomedical field such as drug delivery or single cell manipulation. Herein, a specific potential of the sperm-driven micro-bio-robot is described that might have impact on the development of assisted reproductive technologies.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Objective: The aim of this study was to develop and optimize a transdermal gel formulation of valsartan using Box-Behnken design and to evaluate it for pharmacokinetic study. Methods: The independent variables were Carbopol 940 (X 1), PEG 400 (X 2) and ethanol (X 3) while valsartan flux (Y 1), T lag (Y 2) and gel viscosity (Y 3) were the dependent variables. Iso-eucalyptol was added in all gel formulations as permeation enhancer except for control gel. Results: It was observed that the permeation rate of valsartan significantly increased in direct proportion to the ethanol concentration, but significantly decreased in direct proportion to polymer concentration. Lag time and viscosity decreased in reverse proportion to ethanol concentration. The optimized valsartan gel formulation (VGF-OPT) yielded flux of 143.27 ± 7.11 µg/cm(2)/h and 27.55 ± 2.51 µg/cm(2)/h across rat and human cadaver skin, respectively. In vivo pharmacokinetic study of VGF-OPT-transdermal therapeutic system containing iso-eucalyptol showed a significant increase in the bioavailability (2.52 times) compared with oral formulation of valsartan by virtue of better permeation through Wistar rat skin. Conclusion: It was concluded that the developed transdermal gel accentuates the flux of valsartan and could be used as an antihypertensive dosage form for effective transdermal delivery of valsartan.
    Expert Opinion on Drug Delivery 05/2014;