Ketamine-polymer based drug delivery system for prolonged analgesia: recent advances, challenges and future prospects

ABSTRACT

Introduction: With a sharp increase in NSAIDs and opioid use for chronic pain conditions associated with traumatic injuries and diseases, there has been an escalated risk of life-threatening side effects (cardiac and respiratory malfunction), inadvertent overdose, and even death. Their short duration of action and toxicity induces the need to develop extended-release analgesic drug formulations based on safe drugs like ketamine.

Areas covered: This review presents progressive breakthroughs in pain control strategies for augmenting patient’s comfort and minimizing unnecessary adverse effects associated with NSAIDs and opioids. Advantages of using ketamine, a dissociative anesthetic and potent analgesic over opioids have been elaborated here for the development of advanced sustained-release analgesic drug formulations based on ketamine and polymers (hydrogels, microparticles, and nanoparticles) as mainstream systems. These systems can be very promising in the resource-constrained healthcare set-up where frequent drug dosing at short time intervals is extremely challenging. PubMed, Embase, Google Scholar electronic databases, and clinical websites were used for conducting extensive research.

Expert opinion: Controlled drug release analgesic systems can significantly reduce the burden of repeated drug dosing and opioid drug dependency, maximizing the function of analgesic drugs for clinical translation, and improving the quality of life of those living with pain.

KEYWORDS:

• Ketamine
• sustained drug release
• pain management
• anesthetic
• polymeric hydrogels
• nanoparticles

Article highlights

• New approach of ketamine conjugation to polymeric drug carriers is a comparatively safer and effective method for pain control in comparison to opioids and NSAIDs use.

• Ketamine incorporated polymeric hydrogels/microparticles/nanoparticles/transdermal patches result in higher drug loading together with tunable sustained drug release profile.

• Drug release can vary from few hours to several days by varying drug/polymer type and ratio, hydrophilicity/hydrophobicity of polymer, the functionality of polymeric moieties, and co-polymer stereochemistry.

• Extended drug release using ketamine-polymer conjugates provides prolonged analgesia with a minimized frequency of drug dosing and improved patient’s compliance.

• Rapid and long-lasting pain relief achieved using ketamine-polymer conjugates may lead to reduced psychological burden of pain in patients suffering from post-traumatic stress disorder.

• This combinatorial approach may act like a non-opioid analgesic therapy and has the potential to probably replace or augment the effect of existing treatment options.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.