title: Development and applications of injectable poly(ortho esters) for pain control and periodontal treatment.
abstract: Poly(ortho esters) with a low glass transition temperature are semi-solid materials so that therapeutic agents can be incorporated at room temperature, without the use of solvents, by a simple mixing procedure. When molecular weights are limited to < 5 kDa, such materials are directly injectable using a needle size no larger than 22 gauge. Somewhat hydrophilic polymers can be produced by using the diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane and triethylene glycol (TEG), while hydrophobic materials can be produced by using the diketene acetal and 1,10-decanediol. Molecular weight can be reproducibly controlled by using an excess of the diol, or by use of an alcohol that acts as a chain-stopper. Erosion rates can be controlled by varying the amount of latent acid incorporated into the polymer backbone. Toxicology studies using the TEG polymer have been completed and have shown that the polymer is non-toxic. Toxicology studies using the decanediol polymer are underway. Development studies using the TEG polymer aimed at providing a sustained delivery of an analgesic agent to control post-surgical pain are under development and human clinical trials using the decanediol polymer for the treatment of periodontitis are also underway.
authors.affiliation: Faculty of Medicine, Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University of Jerusalem, Israel. jheller@appharma.com
authors.forename: J
authors.initials: J
authors.lastname: Helle
authors.forename: J
authors.initials: J
authors.lastname: Barr
authors.forename: S Y
authors.initials: SY
authors.lastname: Ng
authors.forename: H R
authors.initials: HR
authors.lastname: Shen
authors.forename: K
authors.initials: K
authors.lastname: Schwach-Abdellaoui
authors.forename: R
authors.initials: R
authors.lastname: Gurny
authors.forename: N
authors.initials: N
authors.lastname: Vivien-Castioni
authors.forename: P J
authors.initials: PJ
authors.lastname: Loup
authors.forename: P
authors.initials: P
authors.lastname: Baehni
authors.forename: A
authors.initials: A
authors.lastname: Mombelli
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry*; D002045:Bupivacaine / Q000008:administration & dosage*; D004285:Dogs; D004337:Drug Carriers; D005233:Fatty Alcohols / Q000494:pharmacology; D005881:Gingiva / Q000187:drug effects; D005898:Glass; D006801:Humans; D007267:Injections; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010146:Pain / Q000188:drug therapy*; D010510:Periodontal Diseases / Q000188:drug therapy*; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000494:pharmacology; D013696:Temperature; D013752:Tetracycline / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D001672:Biocompatible Materials; D004337:Drug Carriers; D005233:Fatty Alcohols; D011091:Polyesters; D011108:Polymers; D012997:Solvents; C028914:triethylene glycol; D011092:Polyethylene Glycols; C118975:1,10-decanediol; D013752:Tetracycline; D002045:Bupivacaine