Evolution of implantable and insertable drug delivery systems

Kleiner, Lothar W.; Wright, Jeremy C.; Wang, Yunbing

doi:10.1016/j.jconrel.2014.02.006

Cited by 150 publications

(108 citation statements)

References 51 publications

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“…New drug delivery technologies, such as removable solid or semi-solid implants, may alleviate many of these problems by providing options that are readily removable. 36 …”

Section: Discussionmentioning

confidence: 99%

Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges

Swindells

Siccardi

Barrett

et al. 2018

int j tuberc lung dis

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SUMMARY Long-acting/extended release drug formulations have proved very successful in diverse areas of medicine including contraception, psychiatry, and most recently, HIV disease. While challenging, application of this technology to TB treatment could have substantial impact. The length of treatment required for all forms of TB put existing regimens at risk for failure because of early discontinuations and treatment default. Long-acting injections, for example administered monthly, could improve patient adherence and treatment outcomes. We review the state of the science for potential long-acting formulations of existing TB drugs, and propose a Target Product Profile for new formulations to treat latent TB infection. The physicochemical properties of some TB drugs make them unsuitable for long-acting formulation, but there are promising candidates that have been identified through modeling and simulation, and other novel agents and formulations in preclinical testing. An efficacious long-acting treatment for latent TB infection, particularly for those co-infected with HIV, and if coupled with a biomarker to target those at highest risk for disease progression, would be an important tool to accelerate progress towards TB elimination.

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“…New drug delivery technologies, such as removable solid or semi-solid implants, may alleviate many of these problems by providing options that are readily removable. 36 …”

Section: Discussionmentioning

confidence: 99%

Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges

Swindells

Siccardi

Barrett

et al. 2018

int j tuberc lung dis

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“…[ 17 ] This technology has been used for oral and transdermal delivery systems, as well as for ocular, vascular, and oncology implants. [ 11,16,18,19 ] Diffusion-based drug delivery systems are created from either non-biodegradable solids such as polyvinyl alcohol (PVA), ethylene-vinyl acetate (EVA), and polysulfone capillary fi ber (PCF), or from biodegradable materials such as polylactic acid (PLA), polyglycolide acid (PGA), polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and polyanhydride. [ 20 ] For each specifi c application, the properties of the materials, as well as the intended drug, should be carefully considered.…”

Section: Diffusion-basedmentioning

confidence: 99%

MEMS: Enabled Drug Delivery Systems

Cobo

Sheybani

Meng

2015

Adv Healthcare Materials

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Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.

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“…Drug delivery systems are engineered technologies for loading and releasing a drug in a predetermined manner to maintain the drug level for a defined time period or targeting a specific site in the body (López-Periago, Argemí et al 2009). Compared with conventional oral or intravascular/intramuscular administration of drug, these so-called "smart" or "intelligent" systems are designed to control drug release kinetics, enhance drug solubility, prolong bioactivity, improve drug efficacy, decrease the high dose administration and overcome toxic side effects (Kleiner, Wright et al 2014). In addition, these systems can improve patient compliance due to less frequent drug administration and the avoidance of systemic circulation of drugs (Wolinsky, Colson et al 2012).…”

Section: Introduction Of Implantable Drug Delivery Systemsmentioning

confidence: 99%

“…Research into implantable drug delivery systems originated in the 1960s, when silicones were used by Folkman to control drug release and prolong systemic drug administration based on the diffusion of small molecules Long 1964, Folkman, Long et al 1966). In 1990, the approval of the device Norplant® by the FDA accelerated the developing implantable drug delivery systems (Kleiner, Wright et al 2014). The increase in the number of commercialized products shows the great potential of implanted drug delivery systems.…”

Section: Introduction Of Implantable Drug Delivery Systemsmentioning

confidence: 99%

“…It is difficult for many experimental systems to enter the clinic. Some of the major problems that need to be overcome include stability, reproducibility, toxicity, and lack of biocompatibility (Kleiner, Wright et al 2014). Nevertheless, several implantable drug delivery systems have been commercial available including non-degradable and biodegradable systems.…”

Section: Introduction Of Implantable Drug Delivery Systemsmentioning

confidence: 99%

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Delivery of therapeutic peptides from thermoplastic polyurethane films

Zhang¹

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Thermoplastic polyurethanes (TPUs) are widely used in biomedical applications due to their excellent mechanical properties and biocompatibility. Their roles as matrices to incorporate therapeutics have been investigated in different areas. With the advance of peptides as therapeutics, there is critical need for investigating delivery of peptides using drug delivery systems. However, there is little work on understanding the release of peptides from TPUs. The aim of this study is to understand how therapeutic peptides might be incorporated and released from TPUs.Initially, we compared the effect of supercritical carbon dioxide treatment and solvent casting on the loading and release of model drugs from polyurethane films. We found that scCO2 treatment may cause a shift of hard segment to the surface of film, but this treatment did not significantly affect physical properties of TPUs. This rearrangement of hard segment caused by scCO2 may affect drug release. We then examined the loading and release of 3 model drugs using scCO2 and compared with solvent casting. ScCO2 was able to load all these 3 model drugs consistently and homogeneously into the films, and the release of these 3 drugs was qualitatively similar by scCO2 or solvent casting.However, the amount of drug accumulated in the films by scCO2 was much less than the total amount of drug in the reaction vessel. This could be a practical limitation for therapeutics such as peptides that are expensive to synthesise. In addition, we found the composition of hard and soft segments may contribute greatly to the efflux of drugs.On the basis of these results, we next investigated the in vitro efflux of peptides from polyurethane films by solvent casting. Interestingly, we found there was a correlation between cumulative release and molecular weight of the peptides. Because one of the causes of implant failure is localised inflammation, we were specifically interested in the delivery of C5aR antagonists from TPU films. First, we found that cyclic peptides may be more stable under harsh casting conditions (elevated temperatures, organic solvents) compared to the linear peptides. Mild conditions are required to retain the bioactivity of peptides. Interestingly, similar to the efflux results of model drugs, the release profiles of peptides were also dependent on the composition of hard and soft segments of TPUs. We also found serum proteins in the medium could facilitate the release of peptides. In addition, in vitro bioactivity of the released peptides was examined by measuring intercellular Ca 2+ concentration mobilization in a cell model of C5a receptor signaling. The ii results demonstrate that released peptides retained their bioactivity. To better control the efflux of peptides, we examined blending of different TPUs. We found that the initial rate and extent of drug released from Tecoflex 80A was significant suppressed by increasing the amount of ElastEon 5325 in the blend. These results offer a simple approach for controlling drug release from TPUs.Furt...

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Evolution of implantable and insertable drug delivery systems

Cited by 150 publications

References 51 publications

Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges

Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges

MEMS: Enabled Drug Delivery Systems

Delivery of therapeutic peptides from thermoplastic polyurethane films

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