Abstract
Precise delivery of therapeutics to the target structures is essential for treatment efficiency and safety. Drug administration via conventional routes requires overcoming multiple transport barriers to achieve and maintain the local drug concentration and commonly results in unwanted off-target effects. Patients’ compliance with the treatment schedule remains another challenge. Implantable drug delivery systems (IDDSs) provide a way to solve these problems. IDDSs are bioengineering devices surgically placed inside the patient’s tissues to avoid first-pass metabolism and reduce the systemic toxicity of the drug by eluting the therapeutic payload in the vicinity of the target tissues. IDDSs present an impressive example of successful translation of the research and engineering findings to the patient’s bedside. It is envisaged that the IDDS technologies will grow exponentially in the coming years. However, to pave the way for this progress, it is essential to learn lessons from the past and present of IDDSs clinical applications. The efficiency and safety of the drug-eluting implants depend on the interactions between the device and the hosting tissues. In this review, we address this need and analyze the clinical landscape of the FDA-approved IDDSs applications in the context of the foreign body reaction, a key aspect of implant–tissue integration.
Highlights
A prospective study evaluated the phenotypes of immune cells surrounding the implants and clearly demonstrated that the numbers of CD8+ and CD68+ cells were significantly higher in this tissue than in control resected tissues without the Implantable drug delivery systems (IDDSs)
IDDSs represent a very attractive therapeutic strategy that bypasses the limitations of the conventional drug administration routes
The avalanche of clinical trials for the new IDDSs is anticipated to occur in the near future
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. While there is no established classification of IDDS, a few categories such as biodegradable and non-biodegradable devices, passive (inserts and stents) and dynamic (pumps) implants, electromechanical and reservoir-based systems, polymer-, or hydrogel-based ones, as well as location-specific implants such as ocular, subcutaneous, intracranial, etc., have been specified This list, includes the clinically approved devices, and those in various preclinical stages and in clinical trials. The peri-implant granulation tissue formed by capillary loops and fibroblasts starts to differentiate from the bone marrow progenitors, blood vessel pericytes, and endothelial cells or migrate from surrounding tissues, resulting in the gradual maturation of the granulations and their transformation in more and more dense connective tissue This stage is characterized by the active synthesis of ECM structural proteins, such as fibrillar collagens and associated glycoproteins. The exclusion criteria involved registered devices providing bolus drug release (e.g., infuse bone graft), as well as tablets, capsules, vaginal rings, intrauterine systems, skin patches, insulin pump inserts, vaccines, retard and depot forms of drugs, as well as various non-surgically placeable long-lasting drug delivery systems
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