title: Surface engineering of porous silicon microparticles for intravitreal sustained delivery of rapamycin.
abstract: OBJECTIVE
  To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system.
  
  
  METHODS
  Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization.
  
  
  RESULTS
  The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls.
  
  
  CONCLUSIONS
  Porous silicon-based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina.
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center, University of California, San Diego, California, United States Department of Chemistry and Biochemistry, University of California, San Diego, California, United States.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Nieto
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center, University of California, San Diego, California, United States.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center, University of California, San Diego, California, United States Department of Ophthalmology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Moon
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, California, United States Department of Bioengineering, University of California, San Diego, California, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sailor
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center, University of California, San Diego, California, United States.
authors.forename: William R
authors.initials: WR
authors.lastname: Freeman
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center, University of California, San Diego, California, United States.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D016062:Porosity; D011817:Rabbits; D012825:Silicon; D020123:Sirolimus / Q000008:administration & dosage*; D013499:Surface Properties
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D020123:Sirolimus; D012825:Silicon
keywords: drug loading and release; hydrosilylation; intravitreal drug delivery; oxidation; porous silicon; rabbit eye; silanization; sirolimus; surface chemistry; sustained release