Novel Polymeric Bioerodable Microparticles for Prolonged‐Release Intrathecal Delivery of Analgesic Agents for Relief of Intractable Cancer‐Related Pain. Issue 7 (19th May 2015)

• Record Type: Journal Article
• Authors: Han, Felicity Y.; Thurecht, Kristofer J.; Lam, Ai‐Leen; Whittaker, Andrew K.; Smith, Maree T.
• Is Part Of: Journal of pharmaceutical sciences. Volume 104:Issue 7(2015:Jul.)
• Page Start: 2334
• Page End: 2344
• Publication Date: 2015-05-19
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24497
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Intractable cancer‐related pain complicated by a neuropathic component due to nerve impingement is poorly alleviated even by escalating doses of a strong opioid analgesic. To address this unmet medical need, we developed sustained‐release, bioerodable, hydromorphone (potent strong opioid)‐ and ketamine (analgesic adjuvant)‐loaded microparticles for intrathecal (i.t.) coadministration. Drug‐loaded poly(lactic‐co‐glycolic acid) (PLGA) microparticles were prepared using a water‐in‐oil‐in‐water method with evaporation. Encapsulation efficiency of hydromorphone and ketamine in PLGA (50:50) microparticles was 26% and 56%, respectively. Microparticles had the desired size range (20–60 μm) and <italic>in vitro</italic> release was prolonged at ≥28 days. Microparticles were stable for ≥6 months when stored refrigerated protected from light in a desiccator. Desirably, i.t. injected fluorescent dye‐labeled PLGA microparticles in rats remained in the lumbar region for ≥7 days. In a rat model of neuropathic pain, i.t. coinjection of hydromorphone‐ and ketamine‐loaded microparticles (each 1 mg) produced analgesia for 8 h only. Possible explanations include inadequate release of ketamine and/or hydromorphone into the spinal fluid, and/or insufficient ketamine loading to prevent development of analgesic tolerance to the released hydromorphone. As sub‐analgesic doses of i.t. ketamine at 24–48 h intervals restored analgesia on each occasion, insufficient ketamine loading appears problematic. We will investigate these issues in future work. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2334–2344, 2015</p> </abstract>