Biodegradable injectable in situ forming drug delivery systems.

The ability to inject a drug incorporated into a polymer to a localized site and have the polymer form a semi-solid drug depot has a number of advantages. Among these advantages is ease of application and localized, prolonged drug delivery. For these reasons a large number of in situ setting polymeric delivery systems have been developed and investigated for use in delivering a wide variety of drugs. In this article we introduce the various strategies that have been used to prepare in situ setting systems, and outline their advantages and disadvantages as localized drug delivery systems.

[1]  Localized intravascular protein delivery from photopolymerized hydrogels , 1995 .

[2]  H. Burt,et al.  Development of a Polymeric Surgical Paste Formulation for Taxol , 1996, Pharmaceutical Research.

[3]  Alexander V. Kabanov,et al.  Effects of Pluronic Block Copolymers on Drug Absorption in Caco-2 Cell Monolayers , 1998, Pharmaceutical Research.

[4]  Jeffrey A. Hubbell,et al.  Hydrogel systems for barriers and local drug delivery in the control of wound healing , 1996 .

[5]  R. Levy,et al.  Controlled release implant dosage forms for cardiac arrhythmias: Review and perspectives. , 1996, Drug delivery.

[6]  N. Udupa,et al.  Biodegradable Injectable Implant Systems for Long Term Drug Delivery Using Poly (Lactic‐co‐glycolic) Acid Copolymers , 1996, The Journal of pharmacy and pharmacology.

[7]  A. Bonetti,et al.  An extended-release formulation of methotrexate for subcutaneous administration , 2004, Cancer Chemotherapy and Pharmacology.

[8]  P. Messersmith,et al.  Thermally Triggered Gelation of Alginate for Controlled Release , 1998 .

[9]  T. Allen,et al.  Subcutaneous administration of liposomes: a comparison with the intravenous and intraperitoneal routes of injection. , 1993, Biochimica et biophysica acta.

[10]  R H Williams,et al.  Poloxamer 407-mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection to rats. , 1992, Journal of parenteral science and technology : a publication of the Parenteral Drug Association.

[11]  D. Wood Biodegradable drug delivery systems , 1980 .

[12]  M. Radomsky,et al.  Sustained-Release Injectable Products , 2000 .

[13]  Ron,et al.  Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. , 1998, Advanced drug delivery reviews.

[14]  D. Maysinger,et al.  Copolymer drug carriers : conjugates, micelles and microspheres , 1999 .

[15]  C. G. Pitt Poly-ε-caprolactone and its copolymers , 1990 .

[16]  Y. Bae,et al.  In situ gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions and degradation thereof. , 2000, Journal of biomedical materials research.

[17]  J. Rosenquist,et al.  Morphological changes in bone following intramedullary implantation of methyl methacrylate. Effects of medullary occlusion: a morphometrical study. , 1983, Acta orthopaedica Scandinavica.

[18]  T. Nakamura,et al.  Evaluation of a novel alginate gel dressing: cytotoxicity to fibroblasts in vitro and foreign-body reaction in pig skin in vivo. , 1998, Journal of biomedical materials research.

[19]  T. Burke,et al.  Stabilization of 10-Hydroxycamptothecin in Poly(lactide-co-glycolide) Microsphere Delivery Vehicles , 1997, Pharmaceutical Research.

[20]  Thomas O'Hara,et al.  A REVIEW OF METHODS USED TO COMPARE DISSOLUTION PROFILE DATA , 1998 .

[21]  J. Eliassaf Aqueous solutions of poly(N-isopropylacrylamide) , 1978 .

[22]  S. Engström,et al.  Phase behaviour of the lidocaine-monoolein-water system , 1992 .

[23]  I. E. Ruyter,et al.  Composites for use in posterior teeth: composition and conversion. , 1987, Journal of biomedical materials research.

[24]  Teruo Okano,et al.  Soluble Self-Assembled Block Copolymers for Drug Delivery , 1999, Pharmaceutical Research.

[25]  R. Gurny,et al.  Bioerodible polymers for ocular drug delivery. , 1998, Critical reviews in therapeutic drug carrier systems.

[26]  H. G. Schild Poly(N-isopropylacrylamide): experiment, theory and application , 1992 .

[27]  R. Bhardwaj,et al.  Controlled‐release delivery system for the α‐MSH analog Melanotan‐I using poloxamer 407 , 1996 .

[28]  K. Anseth,et al.  A review of photocrosslinked polyanhydrides: in situ forming degradable networks. , 2000, Biomaterials.

[29]  J. Cleland,et al.  Stable Formulations of Recombinant Human Growth Hormone and Interferon-γ for Microencapsulation in Biodegradable Mircospheres , 1996, Pharmaceutical Research.

[30]  Shao-Tang Sun,et al.  Phase transitions in ionic gels , 1980 .

[31]  P. Tarkkila,et al.  Controlled Release Gel of Ibuprofen and Lidocaine in Epidural Use—Analgesia and Systemic Absorption in Pigs , 1998, Pharmaceutical Research.

[32]  J. Hughes,et al.  In Situ Gel Formulations for Gene Delivery: Release and Myotoxicity Studies , 2000, Pharmaceutical development and technology.

[33]  Russell J. Stewart,et al.  Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains , 1999, Nature.

[34]  Phase Behavior of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymers in Water , 1995 .

[35]  R. Langer,et al.  Enzymatically activated microencapsulated liposomes can provide pulsatile drug release , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  P. Alexandridis Amphiphilic copolymers and their applications , 1996 .

[37]  K. Himmelstein,et al.  An in situ gelling system for parenteral delivery , 1996 .

[38]  P. Anderson,et al.  Depot characteristics and biodistribution of interleukin-2 liposomes: importance of route of administration. , 1992, Journal of immunotherapy : official journal of the Society for Biological Therapy.

[39]  J. Harms,et al.  [Experimental studies on heat development in bone during polymerization of bone cement. Intraoperative measurement of temperature in normal blood circulation and in bloodlessness]. , 1974, Archiv fur orthopadische und Unfall-Chirurgie.

[40]  J. Löfroth,et al.  Cubic Phases as Delivery Systems for Peptide Drugs , 1991 .

[41]  T. Okano,et al.  Thermo-sensitive polymers as on-off switches for drug release , 1987 .

[42]  John K. Jackson,et al.  Development of amphiphilic diblock copolymers as micellar carriers of taxol , 1996 .

[43]  R Langer,et al.  New methods of drug delivery. , 1990, Science.

[44]  Christine Allen,et al.  Nano-engineering block copolymer aggregates for drug delivery , 1999 .

[45]  Alexander T. Florence,et al.  Physicochemical Principles of Pharmacy , 1988 .

[46]  B Mattiasson,et al.  Thermoreactive water-soluble polymers, nonionic surfactants, and hydrogels as reagents in biotechnology. , 1993, Enzyme and microbial technology.

[47]  J. Pezzuto,et al.  A Mixed Micellar Formulation Suitable for the Parenteral Administration of Taxol , 1994, Pharmaceutical Research.

[48]  A. Bennett,et al.  Physico-chemical characterization of a polymeric injectable implant delivery system , 1995 .

[49]  Howard G. Schild,et al.  Microcalorimetric detection of lower critical solution temperatures in aqueous polymer solutions , 1990 .

[50]  A. Florence,et al.  The formulation and stability of multiple emulsions , 1982 .

[51]  T. Johnston,et al.  Mechanism of poloxamer 407-induced hypertriglyceridemia in the rat. , 1993, Biochemical pharmacology.

[52]  Ronald A. Siegel,et al.  pH-Dependent Equilibrium Swelling Properties of Hydrophobic Polyelectrolyte Copolymer Gels , 1988 .

[53]  D. V. Von Hoff,et al.  A polymer-based drug delivery system for the antineoplastic agent bis(maltolato)oxovanadium in mice. , 1997, British Journal of Cancer.

[54]  P. Burger,et al.  Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma. , 1994, Cancer research.

[55]  R. Dunn,et al.  In Situ Gelling Systems , 2000 .

[56]  A. Lansdown,et al.  An evaluation of the local reaction and biodegradation of calcium sodium alginate (Kaltostat) following subcutaneous implantation in the rat. , 1994, Journal of the Royal College of Surgeons of Edinburgh.

[57]  J. Blanchard,et al.  Evaluation of pluronic F127-based sustained-release ocular delivery systems for pilocarpine using the albino rabbit eye model. , 1998, Journal of pharmaceutical sciences.

[58]  L. Hollister Site-specific drug delivery to CNS: Old and new , 1989, Neurobiology of Aging.

[59]  K. Audus,et al.  Comparison of the effects of potential parenteral vehicles for poorly water soluble anticancer drugs (organic cosolvents and cyclodextrin solutions) on cultured endothelial cells (HUV-EC). , 1998, Journal of pharmaceutical sciences.

[60]  R C Fu,et al.  The biocompatibility of parenteral vehicles--in vitro/in vivo screening comparison and the effect of excipients on hemolysis. , 1987, Journal of parenteral science and technology : a publication of the Parenteral Drug Association.

[61]  R. Agarwal,et al.  Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. , 2000, Carcinogenesis.

[62]  Y. Bae,et al.  Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[63]  F. Agnely,et al.  Controlled release of vancomycin from poloxamer 407 gels. , 1999, International journal of pharmaceutics.

[64]  T. A. Hatton,et al.  Poly(ethylene oxide)-poly(propylene oxide )-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling , 1995 .

[65]  M. Crowther,et al.  The evaluation of glycofurol as a vehicle for use in toxicity studies , 1997 .

[66]  N. Peppas Hydrogels in Medicine and Pharmacy , 1987 .

[67]  E. Lobel,et al.  A novel in situ-forming ophthalmic drug delivery system from alginates undergoing gelation in the eye , 1997 .

[68]  W. Millard,et al.  Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systems. , 2001, International journal of pharmaceutics.

[69]  Wim E. Hennink,et al.  Novel Self-assembled Hydrogels by Stereocomplex Formation in Aqueous Solution of Enantiomeric Lactic Acid Oligomers Grafted To Dextran , 2000 .

[70]  J. Rodriguez,et al.  Biocompatibility of a biodegradable in situ forming implant system in rhesus monkeys. , 1999, Journal of biomedical materials research.

[71]  J. Kost,et al.  Characterization of a polymeric PLGA-injectable implant delivery system for the controlled release of proteins. , 2000, Journal of biomedical materials research.

[72]  Sung Wan Kim,et al.  Biodegradable block copolymers as injectable drug-delivery systems , 1997, Nature.

[73]  Y. Bae,et al.  New biodegradable polymers for injectable drug delivery systems. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[74]  S. Shalaby,et al.  Tailored polymeric materials for controlled delivery systems , 1998 .

[75]  D. Attwood,et al.  Antitumor effect of pluronic F-127 gel containing mitomycin C on sarcoma-180 ascites tumor in mice. , 1992, Chemical & pharmaceutical bulletin.

[76]  J. A. Hubbell,et al.  Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention. , 1994, Journal of biomedical materials research.

[77]  D. Wirtz,et al.  Reversible hydrogels from self-assembling artificial proteins. , 1998, Science.

[78]  W. Hunter,et al.  Release of taxol from poly(ϵ-caprolactone) pastes: effect of water-soluble additives , 1997 .

[79]  D. Attwood,et al.  Xyloglucan gels as sustained release vehicles for the intraperitoneal administration of mitomycin C , 1998 .

[80]  A. Mikos,et al.  Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate. , 2000, Biomaterials.

[81]  Kreuter,et al.  Preparation, characterization and cytotoxicity of methylmethacrylate copolymer nanoparticles with a permanent positive surface charge. , 1997, International journal of pharmaceutics.

[82]  P. Knowles,et al.  Cooperativity of the phase transition in single- and multibilayer lipid vesicles. , 1977, Biochimica et biophysica acta.

[83]  K. Reddy,et al.  Controlled-Release, Pegylation, Liposomal Formulations: New Mechanisms in the Delivery of Injectable Drugs , 2000, The Annals of pharmacotherapy.

[84]  N. Udupa,et al.  Enhanced Antitumour Efficacy of Methotrexate Poly(lactic-co-glycolic) Acid Injectable Gel Implants in Mice Bearing Sarcoma-180 , 1997 .

[85]  A. J. Spiegel,et al.  USE OF NONAQUEOUS SOLVENTS IN PARENTERAL PRODUCTS. , 1963, Journal of pharmaceutical sciences.

[86]  Robert G Laughlin,et al.  The Aqueous Phase Behavior of Surfactants , 1994 .

[87]  R. Gurny,et al.  A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application. , 2000, Journal of biomedical materials research.

[88]  J. Irache,et al.  Poly(ε-caprolacton) nanospheres as an alternative way to reduce amphotericin B toxicity , 1997 .

[89]  M. Irie Stimuli-responsive poly(N-isopropylacrylamide). Photo- and chemical-induced phase transitions , 1993 .

[90]  R. Bodmeier,et al.  Effect of dissolution media and additives on the drug release from cubic phase delivery systems , 1997 .

[91]  R. Langer,et al.  Biodegradable polymers as drug delivery systems , 1990 .

[92]  K. Jacobson,et al.  Phase transitions in phospholipid vesicles. Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol. , 1973, Biochimica et biophysica acta.

[93]  J. Heller Polymers for controlled parenteral delivery of peptides and proteins , 1993 .

[94]  K. Peck,et al.  Development of an in situ forming biodegradable poly-lactide-coglycolide system for the controlled release of proteins , 1995 .

[95]  J. Hubbell,et al.  Inhibition of thrombosis and intimal thickening by in situ photopolymerization of thin hydrogel barriers. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[96]  Kevin E. Healy,et al.  Synthesis and characterization of injectable poly(N-isopropylacrylamide)-based hydrogels that support tissue formation in vitro , 1999 .

[97]  A. Kabanov,et al.  Hypersensitization of multidrug resistant human ovarian carcinoma cells by pluronic P85 block copolymer. , 1996, Bioconjugate chemistry.

[98]  P. Painter,et al.  Fundamentals of Polymer Science , 2019 .

[99]  J. Yliruusi,et al.  Controlled release and dura mater permeability of lidocaine and ibuprofen from injectable poloxamer-based gels. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[100]  L. C. Collins-Gold,et al.  Parenteral emulsions for drug delivery , 1990 .

[101]  J. Kost,et al.  Delivery of Soluble Tumor Necrosis Factor Receptor from In-Situ Forming PLGA Implants: In-Vivo , 2000, Pharmaceutical Research.

[102]  A. Mikos,et al.  Development of Poly(Propylene Fumarate-co-Ethylene Glycol) as an Injectable Carrier for Endothelial Cells , 1999, Cell transplantation.

[103]  R. Tarantino,et al.  A biodegradable injectable implant for delivering micro and macromolecules using poly (lactic-co-glycolic) acid (PLGA) copolymers , 1993 .

[104]  G. Storm,et al.  Administration of liposomal agents and the phagocytic function of the mononuclear phagocyte system , 1998 .

[105]  A. Mikos,et al.  In vitro degradation of a poly(propylene fumarate)/β-tricalcium phosphate composite orthopaedic scaffold , 1997 .

[106]  K. Anseth,et al.  Photopolymerization of multilaminated poly(HEMA) hydrogels for controlled release. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[107]  M. G. Fleming,et al.  Photopolymerization of composite resin using the argon laser. , 1999, Journal.

[108]  Raymond C Rowe,et al.  Handbook of Pharmaceutical Excipients , 1994 .

[109]  Smadar Cohen,et al.  Characterization of PLGA microspheres for the controlled delivery of IL-1α for tumor immunotherapy , 1997 .

[110]  Allan S. Hoffman,et al.  Applications of thermally reversible polymers and hydrogels in therapeutics and diagnostics , 1987 .

[111]  Amarnath Sharma,et al.  Liposomes in drug delivery: Progress and limitations , 1997 .

[112]  T. Johnston,et al.  KINETICS OF SOL-TO-GEL TRANSITION FOR POLOXAMER POLYOLS , 1991 .

[113]  J. Leroux,et al.  Novel injectable neutral solutions of chitosan form biodegradable gels in situ. , 2000, Biomaterials.

[114]  Christopher J. Froelich,et al.  Sustained Delivery of Interleukin-2 from a Poloxamer 407 Gel Matrix Following Intraperitoneal Injection in Mice , 1992, Pharmaceutical Research.

[115]  A. Shukla,et al.  Controlled Release of Contraceptive Steroids from Biodegradable and Injectable Gel Formulations: In Vivo Evaluation , 1995, Pharmaceutical Research.

[116]  A. Kabanov,et al.  Interactions of pluronic block copolymers with brain microvessel endothelial cells: evidence of two potential pathways for drug absorption. , 1997, Bioconjugate chemistry.

[117]  S. Moghimi Opsono-recognition of liposomes by tissue macrophages , 1998 .

[118]  L. D. Taylor,et al.  Preparation of films exhibiting a balanced temperature dependence to permeation by aqueous solutions—a study of lower consolute behavior , 1975 .

[119]  W. Hunter,et al.  Development of biodegradable polymeric paste formulations for taxol: An in vitro and in vivo study , 1996 .

[120]  A. Alam,et al.  Tephrosia purpurea Ameliorates Benzoyl Peroxide-induced Cutaneous Toxicity in Mice: Diminution of Oxidative Stress , 1999 .

[121]  W. Hunter,et al.  The suppression of human prostate tumor growth in mice by the intratumoral injection of a slow-release polymeric paste formulation of paclitaxel. , 2000, Cancer research.

[122]  E. Kalso,et al.  Controlled Release of Lidocaine from Injectable Gels and Efficacy in Rat Sciatic Nerve Block , 1995, Pharmaceutical Research.

[123]  P. Messersmith,et al.  Triggered release of calcium from lipid vesicles: a bioinspired strategy for rapid gelation of polysaccharide and protein hydrogels. , 2001, Biomaterials.

[124]  R. A. Jain,et al.  Controlled release of drugs from injectable in situ formed biodegradable PLGA microspheres: effect of various formulation variables. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[125]  Toyoichi Tanaka,et al.  Volume‐phase transitions of ionized N‐isopropylacrylamide gels , 1987 .

[126]  R L Binder,et al.  Comparison of the skin tumor-promoting potential of different organic peroxides in SENCAR mice. , 1998, Toxicology and applied pharmacology.

[127]  S. Hirotsu Coexistence of phases and the nature of first-order phase transition in poly-N-isopropylacrylamide gels , 1993 .

[128]  D. Pettit,et al.  Biodegradable polymers for protein and peptide drug delivery. , 1995, Bioconjugate chemistry.

[129]  W. Soskolne Subgingival delivery of therapeutic agents in the treatment of periodontal diseases. , 1997, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[130]  A. Mikos,et al.  Injectable biodegradable materials for orthopedic tissue engineering. , 2000, Biomaterials.

[131]  Brian J. Tighe,et al.  Polymers for biodegradable medical devices. 1. The potential of polyesters as controlled macromolecular release systems , 1986 .