Injectable porous hydroxyapatite microparticles as a new carrier for protein and lipophilic drugs.
Hydroxyapatite (Ca10 (PO4)6(OH)2) is a biodegradable material that forms a major component of bones and teeth. We prepared injectable spherical porous hydroxyapatite microparticles (SP-HAp) as a drug carrier by the spray-drying method. We then examined the usefulness of SP-HAp as a carrier for drugs such as interferon alpha (IFNalpha), testosterone enanthate (TE), and cyclosporin A (CyA). SP-HAp had an average diameter of 5 mum and a porosity of approximately 58%. It could be injected subcutaneously through a 27-gauge needle. SP-HAp was observed to be biodegradable. The speed of degradation of SP-HAp could be regulated by altering the calcination temperature. IFNalpha was adsorbed well to SP-HAp particles, but INFalpha was released faster from the particles, than the particles could degrade in both in vitro and in vivo experiments. Addition of human serum albumin and zinc (reinforcement) to IFNalpha-adsorbed SP-HAp caused marked prolongation of release in vivo. The in vivo release of testosterone enanthate and CyA from SP-HAp preparation, which was easily injectable, was similarly prolonged to that from the oil preparation. In conclusion, the SP-HAp seems to be useful as a biodegradable and subcutaneously injectable drug carrier. It is suggested that the reinforcement of the SP-HAp is very effective on the sustained release of drugs.
Mizushima
Yutaka
Y
DDS Institute, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato, Tokyo 105-8461, Japan. Electronic address: mizushima@ltt.co.jp.
Ikoma
Toshiyuki
T
Biomaterials Center, National Institute for Materials Science, Namiki 1-1, Tsukuba, Ibaraki 305-0044, Japan.
Tanaka
Jyunzo
J
Biomaterials Center, National Institute for Materials Science, Namiki 1-1, Tsukuba, Ibaraki 305-0044, Japan.
Hoshi
Keiko
K
Showa Pharmaceutical University, 3-3165, Hiqashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan.
Ishihara
Tsutomu
T
DDS Institute, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato, Tokyo 105-8461, Japan.
Ogawa
Yasuaki
Y
DDS Institute, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato, Tokyo 105-8461, Japan.
Ueno
Akinori
A
DDS Institute, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato, Tokyo 105-8461, Japan.
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003272:Contraceptive Agents, Male / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007370:Interferon Type I / Q000008:administration & dosage; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures; D016062:Porosity; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012867:Skin / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives
D001672:Biocompatible Materials; D003272:Contraceptive Agents, Male; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D008055:Lipids; D011506:Proteins; D011994:Recombinant Proteins; D013739:Testosterone; C004648:testosterone enanthate; D016572:Cyclosporine; D017886:Durapatite