Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology.
The therapeutic effectiveness of drugs is often limited by the inability to sustain therapeutic levels at the target site. Encapsulation of drugs in multivesicular lipid-based particles for sustained release is a novel approach to improving the pharmacokinetics of drug therapy. This paper reviews the preclinical and clinical literature on the applications and potential therapeutic benefits of DepoFoam technology, a novel sustained-release, injectable drug delivery system. DepoFoam formulations of drugs, including anticancer agents (cytarabine, methotrexate, bleomycin, recombinant interferon alfa, 5-fluorouridine-5'-monophosphate, and others), anti-infective agents (dideoxycytidine, 2'-norcyclic guanosine monophosphate, cidofovir, tobramycin, gentamicin, amikacin), analgesics (morphine, bupivacaine), and macromolecules (insulin, interleukin-2), delivered intrathecally, subcutaneously, intraperitoneally, or intralesionally, provide sustained therapeutic levels of drug at the intended target site and reduce systemic exposure and toxicity. Pharmacokinetic studies have demonstrated that DepoFoam particle encapsulation effectively extends the half-life of drugs, thus prolonging the duration of therapeutic drug concentrations in local tissues or in body spaces into which the encapsulated drug is injected. In the case of cell-cycle phase-specific chemotherapeutic agents, such formulations can improve efficacy and therapeutic ratio. DepoFoam is a promising drug delivery system for sustained release of hydrophilic injectable drugs that has a wide range of potential applications in oncology, infectious disease, analgesia, and other therapeutic areas.
Howell
S B
SB
Department of Medicine and the Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
D000701:Analgesics, Opioid / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage*; D009020:Morphine / Q000008:administration & dosage
D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D000964:Antimetabolites, Antineoplastic; D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D003561:Cytarabine; D009020:Morphine; D008727:Methotrexate