Sustaining intravitreal residence with L-arginine peptide-conjugated nanocarriers

Hao Li, Wenzhong Liu, Christine M. Sorenson, Nader Sheibani, Daniel Albert, Thulani Senanayake, Serguei Vinogradov, Jack Henkin, Hao F. Zhang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE. Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (<50 nm in diameter) conjugated with cationic peptides containing L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous. METHODS. We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week. RESULTS. The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization. CONCLUSIONS. We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.

Original languageEnglish (US)
Pages (from-to)5142-5150
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number12
DOIs
StatePublished - Oct 1 2017

Fingerprint

Arginine
Peptides
Dextrans
Therapeutics
Vitreous Body
Retinal Diseases
Intravitreal Injections
Angiogenesis Inhibitors
Eye Diseases
Poisons
Optical Imaging
Hyaluronic Acid
Glaucoma
Rodentia
Fluorescence
Inflammation
Injections

Keywords

  • Fluorescence imaging
  • Intravitreal drug delivery
  • Nanoparticle

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Sustaining intravitreal residence with L-arginine peptide-conjugated nanocarriers. / Li, Hao; Liu, Wenzhong; Sorenson, Christine M.; Sheibani, Nader; Albert, Daniel; Senanayake, Thulani; Vinogradov, Serguei; Henkin, Jack; Zhang, Hao F.

In: Investigative Ophthalmology and Visual Science, Vol. 58, No. 12, 01.10.2017, p. 5142-5150.

Research output: Contribution to journalArticle

Li, H, Liu, W, Sorenson, CM, Sheibani, N, Albert, D, Senanayake, T, Vinogradov, S, Henkin, J & Zhang, HF 2017, 'Sustaining intravitreal residence with L-arginine peptide-conjugated nanocarriers', Investigative Ophthalmology and Visual Science, vol. 58, no. 12, pp. 5142-5150. https://doi.org/10.1167/iovs.17-22160
Li, Hao ; Liu, Wenzhong ; Sorenson, Christine M. ; Sheibani, Nader ; Albert, Daniel ; Senanayake, Thulani ; Vinogradov, Serguei ; Henkin, Jack ; Zhang, Hao F. / Sustaining intravitreal residence with L-arginine peptide-conjugated nanocarriers. In: Investigative Ophthalmology and Visual Science. 2017 ; Vol. 58, No. 12. pp. 5142-5150.
@article{b2ede1efb5594c048ca14b7b9429b55f,
title = "Sustaining intravitreal residence with L-arginine peptide-conjugated nanocarriers",
abstract = "PURPOSE. Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (<50 nm in diameter) conjugated with cationic peptides containing L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous. METHODS. We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week. RESULTS. The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization. CONCLUSIONS. We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.",
keywords = "Fluorescence imaging, Intravitreal drug delivery, Nanoparticle",
author = "Hao Li and Wenzhong Liu and Sorenson, {Christine M.} and Nader Sheibani and Daniel Albert and Thulani Senanayake and Serguei Vinogradov and Jack Henkin and Zhang, {Hao F.}",
year = "2017",
month = "10",
day = "1",
doi = "10.1167/iovs.17-22160",
language = "English (US)",
volume = "58",
pages = "5142--5150",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "12",

}

TY - JOUR

T1 - Sustaining intravitreal residence with L-arginine peptide-conjugated nanocarriers

AU - Li, Hao

AU - Liu, Wenzhong

AU - Sorenson, Christine M.

AU - Sheibani, Nader

AU - Albert, Daniel

AU - Senanayake, Thulani

AU - Vinogradov, Serguei

AU - Henkin, Jack

AU - Zhang, Hao F.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - PURPOSE. Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (<50 nm in diameter) conjugated with cationic peptides containing L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous. METHODS. We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week. RESULTS. The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization. CONCLUSIONS. We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.

AB - PURPOSE. Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (<50 nm in diameter) conjugated with cationic peptides containing L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous. METHODS. We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week. RESULTS. The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization. CONCLUSIONS. We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.

KW - Fluorescence imaging

KW - Intravitreal drug delivery

KW - Nanoparticle

UR - http://www.scopus.com/inward/record.url?scp=85031717969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031717969&partnerID=8YFLogxK

U2 - 10.1167/iovs.17-22160

DO - 10.1167/iovs.17-22160

M3 - Article

VL - 58

SP - 5142

EP - 5150

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 12

ER -