Human scleral diffusion of anticancer drugs from solution and nanoparticle formulation.
OBJECTIVE
To determine the transscleral permeability of chemotherapeutic drugs vinblastine and doxorubicin for treatment of intraocular tumors, and to compare the use of doxorubicin encapsulated in PLGA and liposome nanoparticles.


METHODS
Human sclera was isolated and mounted in a Lucite chamber. Fluorescently tagged vinblastine (VIN), innately fluorescent free doxorubicin (DOX), PLGA doxorubicin (PLGA-DOX), or Doxil (Tibotec Therapeutics) were added to the episcleral donor chamber. The choroidal side was perfused with Balanced Salt Solution. Perfusate fractions were collected over 24 h and measured for fluorescence. Following the experiment, tissue sections were imaged, underwent a drug wash out procedure, and tissue drug content was analyzed using an LC-MS/MS method.


RESULTS
Within 24 h, a total of 68%, 74%, 29%, and 1.9% of the drug dose from VIN, DOX, PLGA-DOX, and Doxil, respectively, diffused across the sclera. VIN and DOX scleral tissue showed strong fluorescence after 24 h. PLGA-DOX displayed scattered fluorescence, and Doxil indicated minimal fluorescence. LC-MS/MS revealed strong tissue binding of DOX.


CONCLUSIONS
This study suggests both vinblastine and doxorubicin are able to diffuse across human sclera. In addition, PLGA nanoparticles delivered doxorubicin at a slower rate across the sclera, and the liposome preparation resulted in the slowest delivery of drug.
Kim
Esther S
ES
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, USA. esther.soon@gmail.com
Durairaj
Chandrasekar
C
Kadam
Rajendra S
RS
Lee
Sung Jin
SJ
Mo
Yun
Y
Geroski
Dayle H
DH
Kompella
Uday B
UB
Edelhauser
Henry F
HF
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D019344:Lactic Acid; D008081:Liposomes; D008875:Middle Aged; D053758:Nanoparticles / Q000737:chemistry*; D010539:Permeability; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012590:Sclera / Q000378:metabolism*; D013997:Time Factors; D014747:Vinblastine / Q000008:administration & dosage* / Q000378:metabolism
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D008081:Liposomes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014747:Vinblastine; D004317:Doxorubicin