An industry update: the latest developments in therapeutic delivery covering May 2020.

The present industry update covers the period 1-31 May 2020, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature.

An industry update: the latest developments in therapeutic delivery.

The present industry update covers the period 1-30 June 2017, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature. The combination of drug and devices such as improved, safer injectables (see various market reports, companies Adamis and Baxter), patches (Microdermis) and (nano)carriers are moving increasingly from the R&D stage into clinical trials and toward the market. This addresses increased safety and effectiveness requirements, limiting physico-chemical properties of active ingredients, cost-effectiveness and patient comfort through ease of use. Further attention in the market is on local delivery methods (such as intraocular by Icon Bioscience, Glaukos) and the sheer infinite possibilities of nanotechnology such as LDL nanocarriers, microneedles and hydrogel cubes. Another 21st century key technology area is mobile applications (Vital Art and Science) and connected devices (SmartPill, Pop Test Devices) which are increasingly finding their way into the drug delivery field to enable, for example, closed loop monitoring of drug dosing in trials and of patients with their care providers. Not surprisingly companies are increasingly utilizing convergence to combine their diverse capabilities (Vetter Pharma/Microdermis, TXCell/Lentigen Technology).

An industry update: the latest developments in therapeutic delivery.

The present industry update covers the period 1-31 January 2017, with information sourced from company press releases, regulatory and patent agencies as well as the scientific literature. With a new year come new resolutions, annual operation plans but also reports and outlooks for the years(s) to come. A number of the latter have been published in January forecasting various spaces in drug delivery (Market and Research). Also a number of financing deals were closed being fresh into the year such as Ossianix and Ocular Therapeutix and contract manufacturers will show their offerings at the 2017 MD&M West Medtech event (Lubrizol, Trelleborg). The US FDA released some new (draft) guidelines for combination products to regulate standards and disputes in this increasingly important field. Recent advances in artificial pancreas technology demonstrates that while the age of nanotechnology and gene therapy (Bluebird Bio) has arrived, implantable, closed-loop delivery systems (Medtronic) are just to pass successfully the clinic and come in reach of patients.

PET-CT imaging with [(18)F]-gefitinib to measure Abcb1a/1b (P-gp) and Abcg2 (Bcrp1) mediated drug-drug interactions at the murine blood-brain barrier.

INTRODUCTION: The efflux transporters P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) are expressed at the blood-brain barrier (BBB), and can limit the access of a wide range of drugs to the brain. In this study we developed a PET-CT imaging method for non-invasive, quantitative analysis of the effect of ABCB1 and ABCG2 on brain penetration of the anti-cancer drug gefitinib, and demonstrated the applicability of this method for identification and quantification of potential modulators of ABCB1 and ABCB2 using the dual inhibitor elacridar. METHODS: In vitro cellular accumulation studies with [(14)C]-gefitinib were conducted in LLC-PK1, MDCKII, and the corresponding ABCB1/Abcb1a and ABCG2/Abcg2 overexpressing cell lines. Subsequently, in vivo brain penetration of [(18)F]-gefitinib was quantified by PET-CT imaging studies in wild-type, Abcg2(-/-), Abcb1a/1b(-/-), and Abcb1a/1b;Abcg2(-/-) mice. RESULTS: In vitro studies showed that [(14)C]-gefitinib is a substrate of the human ABCB1 and ABCG2 transporters. After i.v. administration of [(18)F]-gefitinib (1mg/kg), PET-CT imaging showed 2.3-fold increased brain levels of [(18)F]-gefitinib in Abcb1a/1b;Abcg2(-/-) mice, compared to wild-type. Levels in single knockout animals were not different from wild-type, showing that Abcb1a/1b and Abcg2 together limit access of [(18)F]-gefitinib to the brain. Furthermore, enhanced brain accumulation of [(18)F]-gefitinib after administration of the ABCB1 and ABCG2 inhibitor elacridar (10 mg/kg) could be quantified with PET-CT imaging. CONCLUSIONS: PET-CT imaging with [(18)F]-gefitinib is a powerful tool to non-invasively assess potential ABCB1- and ABCG2-mediated drug-drug interactions (DDIs) in vivo. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This minimally-invasive, [(18)F]-based PET-CT imaging method shows the interplay of ABCB1 and ABCG2 at the BBB in vivo. The method may be applied in the future to assess ABCB1 and ABCG2 activity at the BBB in humans, and for personalized treatment with drugs that are substrates of ABCB1 and/or ABCG2.

Industry Update: the latest developments in therapeutic delivery.

The present Industry Update covers the period 1-28 February 2014, with information sourced from company press releases, regulatory and patent agencies, as well as the scientific literature. February is traditionally the month of annual reports - looking back and looking forward, hence a number of market reports on past, present and future developments in drug delivery were released. An increased trend in deal making for targeted drug delivery, as in 2013, will continue to drive partnerships in 2014. In 2013, the number of drug delivery deals inked in the healthcare industry stood at close to 400 and added up to US$2.3 billion. Closer collaboration or acquisition of drug delivery specialists by 'big pharma' are observed, such as Lupin and Nanomi, Teva and NuPathe, and Novo Nordisk and Zosano Pharma. Alternatively, one can see exclusive intellectual property or distribution rights deals such as MNG Pharma with Samyang Biopharmaceutical or Songry with a USA-based university. A few regulatory delays due to rejection (IntelGenx and Durect) joined the usually reported approvals, and iontophoresis was favorably re-evaluated in a recent US FDA hearing. A number of publications have proven that the sophistication and miniaturization of drug-delivery devices (inner-ear delivery) and particles (triggered supraparamagnetic and 'sticky' particles) is moving further at an ever faster pace.

Initial experience of MR/PET in a clinical cancer center.

Magentic Resonance/positron emission tomography (PET) has been introduced recently for imaging of clinical patients. This hybrid imaging technology combines the inherent strengths of MRI with its high soft-tissue contrast and biological sequences with the inherent strengths of PET, enabling imaging of metabolism with a high sensitivity. In this article, we describe the initial experience of MR/PET in a clinical cancer center along with a review of the literature. For establishing MR/PET in a clinical setting, technical challenges, such as attenuation correction and organizational challenges, such as workflow and reimbursement, have to be overcome. The most promising initial results of MR/PET have been achieved in anatomical areas where high soft-tissue and contrast resolution is of benefit. Head and neck cancer and pelvic imaging are potential applications of this hybrid imaging technology. In the pediatric population, MR/PET can decrease the lifetime radiation dose. MR/PET protocols tailored to different types of malignancies need to be developed. After the initial exploration phase, large multicenter trials are warranted to determine clinical indications for this exciting hybrid imaging technology and thereby opening new horizons in molecular imaging.

Industry Update: the latest developments in therapeutic delivery.

The present industry update covers the period 2-28 February 2013, with information sourced from company press releases, regulatory and patent agencies, as well as from scientific literature. With the US presidential inauguration in January, the inevitable 'fiscal cliff' and with the healthcare reform taking shape, there are many challenges ahead for the world's largest healthcare market. Healthcare providers are preparing for the 'accountable care organizations' paradigm shift and it has been reported that the pharmaceutical industry is low in public perception; only 'for-profit' health insurers rank lower according to a survey recently published. Although in 2012 one could still observe a decline in the overall number of drug delivery partnering deals announced, there has been a slight recovery, thus, meaning a repeat of the lows of 2011 have not been witnessed. The experts expect a reversed trend in 2013 as larger companies seek to refill pipelines with new candidates and drug-delivery solutions. There is a lot of emphasis on altered oral delivery profiles to provide patient compliance. This is indicated by the recent licensing deals, such as that between Radius Health Inc. and 3M, TissueGen and Biomedical Structures, and new financing rounds of companies, such as SKL, Catalent and BioActiva. Injectable technology, including needle-free delivery, continues to be prevalent in deals, such as those between Clearside and Kala until compelling alternatives to the delivery of biologicals are available. Alternative routes of administration, such as nasal, buccal (Kala), sublingual (Stallergenes) see growing interest; however, bioavailability and reproducible dosing will continue to be a challenge in the foreseeable future.

Automated synthesis of [18F]gefitinib on a modular system.

In recent years, [(18)F]gefitinib PET has successfully been employed for a number of applications ranging from oncology to in vivo studies of drug transporter proteins. We here report a reliable, automated procedure for routine synthesis of this radiotracer on an Eckert and Ziegler modular system. The 3-step radiosynthesis followed by preparative HPLC-purification provided [(18)F]gefitinib in 17.2±3.3% (n=22) overall decay-corrected radiochemical yield with radiochemical purity >99% in a total synthesis time of about 2.5h.

Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T.

Iopamidol (Isovue®-Bracco Diagnostic Inc.) is a clinically approved X-Ray contrast agent used in the last 30 years for a wide variety of diagnostic applications with a very good clinical acceptance. Iopamidol contains two types of amide functionalities that can be exploited for the generation of chemical exchange saturation transfer effect. The exchange rate of the two amide proton pools is markedly pH-dependent. Thus, a ratiometric method for pH assessment has been set-up based on the comparison of the saturation transfer effects induced by selective irradiation of the two resonances. This ratiometric approach allows to rule out the concentration effect of the contrast agent and provides accurate pH measurements in the 5.5-7.4 range. Upon injection of Iopamidol into healthy mice, it has been possible to acquire pH maps of kidney regions. Furthermore, it has been also shown that the proposed method is able to report about pH-changes induced in control mice fed with acidified or basified water for a period of a week before image acquisition.

See, reach, treat: ultrasound-triggered image-guided drug delivery.

The integration of therapeutic interventions with diagnostic imaging has been recognized as one of the next technological developments that will have a major impact on medical treatments. Therapeutic applications using ultrasound, for example thermal ablation, hyperthermia or ultrasound-induced drug delivery, are examples for image-guided interventions that are currently being investigated. While thermal ablation using magnetic resonance-guided high-intensity focused ultrasound is entering the clinic, ultrasound-mediated drug delivery is still in a research phase, but holds promise to enable new applications in localized treatments. The use of ultrasound for the delivery of drugs has been demonstrated, particularly in the field of cardiology and oncology for a variety of therapeutics ranging from small-molecule drugs to biologics and nucleic acids exploiting temperature- or pressure-mediated delivery schemes.

Ultrasound triggered image-guided drug delivery.

The integration of therapeutic interventions with diagnostic imaging has been recognized as one of the next technological developments that will have a major impact on medical treatments. Important advances in this field are based on a combination of progress in guiding and monitoring ultrasound energy, novel drug classes becoming available, the development of smart delivery vehicles, and more in depth understanding of the mechanisms of the cellular and molecular basis of diseases. Recent research demonstrates that both pressure sensitive and temperature sensitive delivery systems hold promise for local treatment. The use of ultrasound for the delivery of drugs has been demonstrated in particular the field of cardiology and oncology for a variety of therapeutics ranging from small drug molecules to biologics and nucleic acids.