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The Intraocular Lens as a Drug Delivery Device: In Vitro Screening of Pharmacologic Substances for the Prophylaxis of Posterior Capsule Opacification.

Abstract Numerous pharmacologic substances have been proposed for preventing posterior capsule opacification (PCO). The following trial was to compare those drugs to find more suitable options. IOL should then be modified by the pharmaceuticals as a drug-delivery device.
PMID
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Authors

Mayor MeshTerms

Lenses, Intraocular

Keywords
Journal Title investigative ophthalmology & visual science
Publication Year Start




PMID- 29260197
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20171227
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 14
DP  - 2017 Dec 1
TI  - The Intraocular Lens as a Drug Delivery Device: In Vitro Screening of
      Pharmacologic Substances for the Prophylaxis of Posterior Capsule Opacification.
PG  - 6408-6418
LID - 10.1167/iovs.17-22555 [doi]
AB  - Purpose: Numerous pharmacologic substances have been proposed for preventing
      posterior capsule opacification (PCO). The following trial was to compare those
      drugs to find more suitable options. IOL should then be modified by the
      pharmaceuticals as a drug-delivery device. Methods: A systematic literature
      search was performed to identify published substances. FHL-124 was used to
      determine cell proliferation and toxicity using a dye reduction test (XTT).
      Prescreened substances showing a reduction on cell growth without being toxic
      were soaked into an IOL. Those IOL were tested for their effect on PCO in an
      anterior-segment model and the human ex vivo capsular bag model. Toxicity on a
      corneal endothelial cell line (CEC-SV40) was determined. Release kinetics of
      methotrexate from the IOL was measured. Toxicity testing in both cell lines was
      done in serum-free conditions. All growth assays were exposed to 10% fetal calf
      serum (FCS)-supplemented medium. Results: The substances inhibited cell growth at
      the following EC50: caffeic acid phenethyl ester 1.6 +/- 0.9 nM, disulfiram 359
      +/- 33 nM, methotrexate 98.0 +/- 29.7 nM, rapamycin 70.2 +/- 14.0 pM, and
      retinoic acid 1.1 +/- 0.12 nM. All but disulfiram showed an effect in the
      anterior segment model when soaked into an IOL. Long-term inhibitory effects in
      the human capsular bag model were observed for caffeic acid phenethyl ester and
      methotrexate IOLs. Only methotrexate and disulfiram did not show any toxicity on 
      endothelial cells. Methotrexate was released constantly from the hydrophilic IOL 
      for 2 weeks. Conclusions: We could identify caffeic acid phenethyl ester and
      methotrexate in vitro as potential candidates for IOL modification for PCO
      prophylaxis.
FAU - Wertheimer, Christian
AU  - Wertheimer C
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Kassumeh, Stefan
AU  - Kassumeh S
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Piravej, Nick P
AU  - Piravej NP
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Nilmayer, Olga
AU  - Nilmayer O
AD  - Department of corneal tissue banking, Ludwig-Maximilians-University, Planegg,
      Germany.
FAU - Braun, Christian
AU  - Braun C
AD  - Department for forensic medicine, Ludwig-Maximilians-University, Munchen,
      Germany.
FAU - Priglinger, Claudia
AU  - Priglinger C
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Luft, Nikolaus
AU  - Luft N
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Wolf, Armin
AU  - Wolf A
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Mayer, Wolfgang J
AU  - Mayer WJ
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Priglinger, Siegfried G
AU  - Priglinger SG
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Eibl-Lindner, Kirsten H
AU  - Eibl-Lindner KH
AD  - Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Prescription Drugs)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anterior Eye Segment/drug effects
MH  - Cadaver
MH  - Capsule Opacification/*drug therapy
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Drug Delivery Systems/*methods
MH  - Endothelial Cells/drug effects
MH  - Endothelium, Corneal/cytology
MH  - Female
MH  - Humans
MH  - *Lenses, Intraocular
MH  - Male
MH  - Middle Aged
MH  - Prescription Drugs/*administration &
      dosage/pharmacokinetics/pharmacology/toxicity
MH  - Young Adult
EDAT- 2017/12/21 06:00
MHDA- 2017/12/28 06:00
CRDT- 2017/12/21 06:00
PHST- 2017/12/21 06:00 [entrez]
PHST- 2017/12/21 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
AID - 2667136 [pii]
AID - 10.1167/iovs.17-22555 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Dec 1;58(14):6408-6418. doi:
      10.1167/iovs.17-22555.