← Back to Search
Pharmacology Of Drugs Formulated With DepoFoam™
M. Angst, D. Drover
Published 2006 · Medicine
Download PDFAnalyze on Scholarcy
Lamellar liposome technology has been used for several decades to produce sustained-release drug formulations for parenteral administration. Multivesicular liposomes are structurally distinct from lamellar liposomes and consist of an aggregation of hundreds of water-filled polyhedral compartments separated by bi-layered lipid septa. The unique architecture of multivesicular liposomes allows encapsulating drug with greater efficiency, provides robust structural stability and ensures reliable, steady and prolonged drug release.The favourable characteristics of multivesicular liposomes have resulted in many drug formulations exploiting this technology, which is proprietary and referred to as DepoFoam™. Currently, two formulations using multivesicular liposome technology are approved by the US FDA for clinical use, and many more formulations are at an experimental developmental stage. The first clinically available formulation contains the antineoplastic agent cytarabine (DepoCyt™) for its intrathecal injection in the treatment of malignant lymphomatous meningitis. Intrathecal injection of DepoCyt™ reliably results in the sustained release of cytarabine and produces cytotoxic concentrations in cerebrospinal fluid (CSF) that are maintained for at least 2 weeks. Early efficacy data suggest that DepoCyt™ is fairly well tolerated, and its use allows reduced dosing frequency from twice a week to once every other week and may improve the outcome compared with frequent intrathecal injections of unencapsulated cytarabine. The second available formulation contains morphine (DepoDur™) for its single epidural injection in the treatment of postoperative pain. While animal studies confirm that epidural injection of DepoDur™ results in the sustained release of morphine into CSF, the CSF pharmacokinetics have not been determined in humans. Clinical studies suggest that the use of DepoDur™ decreases the amount of systemically administered analgesics needed for adequate postoperative pain control. It may also provide superior pain control during the first 1–2 postoperative days compared with epidural administration of unencapsulated morphine or intravenous administration of an opioid. However, at this timepoint the overall clinical utility of DepoDur™ has yet to be defined and some safety concerns remain because of the unknown CSF pharmacokinetics of DepoDur™ in humans.The versatility of multivesicular liposome technology is reflected by the many agents including small inorganic and organic molecules and macromolecules including proteins that have successfully been encapsulated. Data concerning many experimental formulations containing antineoplastic, antibacterial and antiviral agents underscore the sustained, steady and reliable release of these compounds from multivesicular liposomes after injection by the intrathecal, subcutaneous, intramuscular, intraperitoneal and intraocular routes. Contingent on the specific formulation and manufacturing process, agents were released over a period of hours to weeks as reflected by a 2- to 400-fold increase in elimination half life. Published data further suggest that the encapsulation process preserves bioactivity of agents as delicate as proteins and supports the view that examined multivesicular liposomes were non-toxic at studied doses. The task ahead will be to examine whether the beneficial structural and pharmacokinetic properties of multivesicular liposome formulations will translate into improved clinical outcomes, either because of decreased drug toxicity or increased drug efficacy.
This paper references
Preparation of multivesicular liposomes.
S. Kim (1983)
Clinical Pharmacology of Encapsulated Sustained-Release Cytarabine
D. J. Murry (2000)
Safety Assessment of Encapsulated Morphine Delivered Epidurally in a Sustained-Release Multivesicular Liposome Preparation in Dogs
T. Yaksh (2000)
Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam.
S. Kim (1993)
Pain as a factor complicating recovery and discharge after ambulatory surgery.
D. J. Pavlin (2002)
Extended CSF cytarabine exposure following intrathecal administration of DTC 101.
S. Kim (1993)
Postoperative Pain Relief by Epidural Morphine
N. Rawal (1981)
Epidural analgesia for postoperative pain.
Jeffrey M. Richman (2005)
Modulation of the sustained delivery of myelopoietin (Leridistim) encapsulated in multivesicular liposomes (DepoFoam).
M. V. Langston (2003)
Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology.
Howell Sb (2001)
Sustained-release methotrexate for intracavitary chemotherapy.
E. Chatelut (1994)
Postoperative analgesia reduces mortality and morbidity after esophagectomy.
S. L. Tsui (1997)
Antinociception and side effects of liposome-encapsulated alfentanil after spinal delivery in rats.
M. Wallace (1994)
Sustained release of cisplatin from multivesicular liposomes: potentiation of antitumor efficacy against S180 murine carcinoma.
C. Xiao (2004)
Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes.
S. Kim (1990)
Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes.
K. Assil (1991)
Efficacy of postoperative epidural analgesia: a meta-analysis.
Brian M. Block (2003)
Pharmacokinetics of DepoFoam gentamicin delivery system and effect on soft tissue infection.
L. S. Grayson (1993)
Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis.
M. Glantz (1999)
Lipid-based slow-release formulation of amikacin sulfate reduces foreign body-associated infections in mice.
A. A. Roehrborn (1995)
An extended-release formulation of methotrexate for subcutaneous administration
A. Bonetti (2004)
Incidence and characteristics of failures in obstetric neuraxial analgesia and anesthesia: a retrospective analysis of 19,259 deliveries.
P. Pan (2004)
Quality improvement guidelines for the treatment of acute pain and cancer pain. American Pain Society Quality of Care Committee.
M. Max (1995)
Multivesicular liposomes for oral delivery of recombinant human epidermal growth factor
H. Li (2005)
Local treatment of prosthetic vascular graft infection with multivesicular liposome-encapsulated amikacin.
J. Huh (1998)
Acute Pain Management: Operative or Medical Procedures and Trauma
S. L. Follin (1997)
Pain intensity and postoperative pulmonary complications among the elderly after abdominal surgery.
R. A. Shea (2002)
The Effect of 1-β-d-Arabinofuranosylcytosine on Growth, Viability, and DNA Synthesis of Mouse L-cells
F. Graham (1970)
Pharmacokinetics Following Intraventricular Administration of Chemotherapy in Patients with Neoplastic Meningitis
G. Fleischhack (2005)
Leptomeningeal metastases: current concepts and management guidelines.
S. Chowdhary (2005)
Pharmacokinetics and efficacy of epidurally delivered sustained-release encapsulated morphine in dogs.
T. Yaksh (1999)
Regional Anesthesia in the Anticoagulated Patient: Defining the Risks (The Second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation)
T. Horlocker (2003)
Multivesicular liposome formulation for the sustained delivery of breviscapine.
Haijun Zhong (2005)
Comparison of the Efficacy of Epidural Morphine Given by Intermittent Injection or Continuous Infusion for the Management of Postoperative Pain
R. Rauck (1993)
Tobramycin liposomes. Single subconjunctival therapy of pseudomonal keratitis.
K. Assil (1991)
Single-Dose Extended-Release Epidural Morphine for Pain Following Hip Arthroplasty
E. Viscusi (2006)
Fibrin-Enmeshed Tobramycin Liposomes: Single Application Topical Therapy of Pseudomonas Keratitis
J. Frucht-Perry (1992)
Pain management after major orthopaedic surgery: current strategies and new concepts.
R. Sinatra (2002)
Thoracic epidural analgesia in coronary artery bypass graft surgery: seven years' experience.
M. Pastor (2003)
Sustained-delivery of an apolipoproteinE-peptidomimetic using multivesicular liposomes lowers serum cholesterol levels
M. Ramprasad (2002)
Multivesicular liposomes containing 1-beta-D-arabinofuranosylcytosine for slow-release intrathecal therapy.
S. Kim (1987)
Postoperative pain management.
S. Jain (1997)
Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: results from a prospective, randomized trial.
L. S. Grayson (1995)
Single-Dose, Sustained-Release Epidural Morphine in the Management of Postoperative Pain After Elective Cesarean Delivery: Results of a Multicenter Randomized Controlled Study
B. Carvalho (2005)
Forty-eight Hours of Postoperative Pain Relief after Total Hip Arthroplasty with a Novel, Extended-Release Epidural Morphine Formulation
E. Viscusi (2005)
Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101). A phase I study.
M. Chamberlain (1993)
Multivesicular liposomes containing cytarabine entrapped in the presence of hydrochloric acid for intracavitary chemotherapy.
S. Kim (1987)
An Open Label Trial of Sustained-release Cytarabine (DepoCyt™) for the Intrathecal Treatment of Solid Tumor Neoplastic Meningitis
K. Jaeckle (2004)
Postoperative Pain Experience: Results from a National Survey Suggest Postoperative Pain Continues to Be Undermanaged
J. Apfelbaum (2003)
Multivesicular liposome (DepoFoam) technology for the sustained delivery of insulin-like growth factor-I (IGF-I).
N. V. Katre (1998)
A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors.
M. Glantz (1999)
Sustained‐release Morphine for Epidural Analgesia in Rats
T. Kim (1996)
A Comparison of Depodur™, a Novel, Single-Dose Extended-Release Epidural Morphine, with Standard Epidural Morphine for Pain Relief After Lower Abdominal Surgery
D. Gambling (2005)
Cytosine arabinoside cerebrospinal fluid kinetics
S. Zimm (1984)
Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases.
M. Chamberlain (1995)
Modulation of the peritoneal clearance of liposomal cytosine arabinoside by blank liposomes
S. Kim (2004)
Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis.
L. Bomgaars (2004)
The risk of infection associated with epidural analgesia.
K. Brooks (1995)
Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium
S. Jain (2008)
RETINAL TOXICITY OF THE ANTIMETABOLITE 5‐FLUOROURIDINE 5'-MONOPHOSPHATE ADMINISTERED INTRAVITREALLY USING MULTIVESICULAR LIPOSOMES
R. Gariano (1994)
Chronic Pain as an Outcome of Surgery: A Review of Predictive Factors
F. Perkins (2000)
Multivesicular liposome formulations for the sustained delivery of interferon α-2b
J. Qiu (2005)
Clinical pharmacology of intrathecal methotrexate. I. Pharmacokinetics in nontoxic patients after lumbar injection.
Bleyer Wa (1977)
Epidural morphine for analgesia after Caesarean section: a report of 4880 patients
John G. Fuller (1990)
Assessment of pain experiences after elective surgery.
I. Svensson (2000)
Leptomeningeal metastases: Comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias
J. G. Kaplan (2012)
Extended-release formulation of morphine for subcutaneous administration
T. Kim (2004)
Distribution of Phospholipids and Triglycerides in Multivesicular Lipid Particles
Jeff F. Ellena (1999)
Evaluation of a single-dose, extended-release epidural morphine formulation for pain after knee arthroplasty.
C. Hartrick (2006)
Sustained release of the antimetabolite 5-fluorouridine-5'-monophosphate by multivesicular liposomes.
K. Assil (1988)
Pharmacokinetics of an extended-release human interferon alpha-2b formulation
A. Bonetti (2004)
The sustained granulopoietic effect of progenipoietin encapsulated in multivesicular liposomes.
M. Ramprasad (2003)
A meta-analysis of the relative efficacy and toxicity of single daily dosing versus multiple daily dosing of aminoglycosides.
M. Z. Ali (1997)
Multivesicular liposomes containing cytarabine for slow-release Sc administration.
S. Kim (1987)
A slow-release methotrexate formulation for intrathecal chemotherapy
E. Chatelut (2004)
Fate of the predominant phospholipid component of DepoFoam drug delivery matrix after intrathecal administration of sustained-release encapsulated cytarabine in rats.
F. R. Kohn (1998)
Quality‐of‐life–adjusted survival comparison of sustained‐release cytosine arabinoside versus intrathecal methotrexate for treatment of solid tumor neoplastic meningitis
B. Cole (2003)
Pain relief and safety after major surgery A prospective study of epidural and intravenous analgesia in 2696 patients
P. Flisberg (2003)
A lipid based depot (DepoFoam technology) for sustained release drug delivery.
S. Mantripragada (2002)
Extended-interval aminoglycoside administration for children: a meta-analysis.
D. Contopoulos-Ioannidis (2004)
Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine
K. Jaeckle (2001)
Touch‐evoked Agitation Produced by Spinally Administered Phospholipid Emulsion and Liposomes in Rats: Structure‐Activity Relation
A. M. Yáñez (1995)
Single or multiple daily doses of aminoglycosides: a meta- analysis
M. Barza (1996)
Multivesicular liposomes containing bleomycin for subcutaneous administration
Romi Roy (2004)
Topology of multivesicular liposomes, a model biliquid foam
M. Spector (1996)
Antinociception and side effects of L- and D-dipalmitoylphosphatidyl choline liposome-encapsulated alfentanil after spinal delivery in rats.
J. Isackson (1995)
This paper is referenced by
The Safety of EXPAREL ® (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs
B. Richard (2012)
Innovations and opportunities to improve conventional (deoxy)nucleoside and fluoropyrimidine analogs in cancer.
A. D. Adema (2009)
In recent years , some researchers focused on searching more appropriate biomaterials to combine with PLGA to solve the above problems
Liandong Hu (2012)
Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy
Yu-Lin Su (2015)
Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems.
J. C. Kraft (2014)
Liposomal Cytarabine as Cancer Therapy: From Chemistry to Medicine
B. Salehi (2019)
Clinical Translation of Nanomedicine.
Y. Min (2015)
Degree of Unsaturation and Backbone Orientation of Amphiphilic Macromolecules Influence Local Lipid Properties in Large Unilamellar Vesicles.
Alysha Moretti (2017)
Maßgeschneiderte Nanopartikel für den Wirkstofftransport in der Krebstherapie
Tianmeng Sun (2014)
Management of accidental spinal administration of extended-release epidural morphine.
J. C. Gerancher (2008)
Inhalable liposomes of low molecular weight heparin for the treatment of venous thromboembolism.
Shuhua Bai (2010)
Pharmacokinetics of multivesicular liposomal encapsulated cytarabine when administered subcutaneously in dogs.
Irene B Vazquez Fuster (2020)
Long-Acting Local Anesthetics for Analgesia Following Thoracic Surgery
Wendell H. WilliamsIII (2019)
Pain Control and Functional Milestones in Total Knee Arthroplasty: Liposomal Bupivacaine versus Femoral Nerve Block
S. Yu (2017)
Recent advances on thermosensitive and pH-sensitive liposomes employed in controlled release.
Marjan Abri Aghdam (2019)
Respiratory Depression after Neuraxial Opioids in the Obstetric Setting
B. Carvalho (2009)
Nanotherapeutics in the EU: an overview on current state and future directions
A. Hafner (2014)
Networking of Smart Drugs: A Chem-Bioinformatic Approach to Cancer Treatment
K. Kesari (2018)
Analytical Utility of Liposomes: From Past to Present
Katie A Edwards (2016)
Light-patterning of synthetic tissues with single droplet resolution
M. J. Booth (2017)
Nicardipine Loaded Solid Phospholipid Extrudates for the Prevention of Cerebral Vasospasms: In Vitro Characterization
Christin Zlomke (2020)
The safety of liposome bupivacaine following various routes of administration in animals
G. Joshi (2015)
Abstracts and Highlight Papers of the 33rd Annual European Society of Regional Anaesthesia & Pain Therapy (ESRA) Congress 2014: Invited Speaker Highlight Papers
Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration
Jing Zou (2017)
Continuous epidural infusion of morphine versus single epidural injection of extended-release morphine for postoperative pain control after arthroplasty: a retrospective analysis
Stephanie Vanterpool (2010)
Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come
Phatsapong Yingchoncharoen (2016)
Emerging roles of liposomal bupivacaine in anesthesia practice
Obaid S Malik (2017)
Science and technology of the emerging nanomedicines in cancer therapy: A primer for physicians and pharmacists
G. Pillai (2013)
Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison
B. Richard (2011)
Analysis of individual patient data from clinical trials: epidural morphine for postoperative pain.
R. N. Mhuircheartaigh (2009)
The Effects of Body Mass Index on Pain Control With Liposomal Bupivacaine in Hip and Knee Arthroplasty.
Abigail L. Campbell (2018)
Release Pattern of Liposomal Bupivacaine in Artificial Cerebrospinal Fluid.
Ayşe Ünal Düzlü (2016)See more