Accumulation of Porcine Insulin in the Rat Brain and Cerebrospinal Fluid Following Ocular Application

Koevary, Steven B.; Lam, Vincent K.; Patsiopoulos, Georgia; Lake, Stephen

doi:10.1089/108076803322279435

Cited by 21 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24,33 In light of our earlier findings of high levels of topically applied peptides in the cerebrospinal fluid (CSF), we previously speculated that these peptides reached the posterior pole of the contralateral eye by diffusing through the CSF that surrounds the optic nerve and chiasm. Our previous data also suggested that while systemic uptake following topical application does occur, it does not influence the levels of peptide recovered in retinal homogenates, nor did it appear in under 30 min 25 ; recall that our working time frame was less than 30 min postapplication. In this study, we were not able to recover measurable amounts of IgG1 from serum at 10 and 20 min after application, though we were able to measure IgG1 in serum that was spiked with antibody (data not shown).…”

Section: Discussionsupporting

confidence: 51%

See 1 more Smart Citation

Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration

Koevary

2016

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Purpose: The purpose of this study was to determine whether nonspecific and ICAM-1-specific IgG1 antibodies can accumulate in the rat retina following topical application, and to develop a model system to show that antibodies that reach the posterior segment retain their pharmacological properties. Methods: Eye drops containing mouse IgG1 or anti-ICAM-1 and the permeation enhancer saponin were topically applied to the eyes of Lewis rats. Concentrations were determined in the retina and optic nerve up to 30 min later using ELISA assays. We also developed an in vitro model to assess the pharmacologic activity of topically delivered antibodies in the retina based on the requirement of human umbilical vein endothelial cells (HUVECs) for vascular endothelial growth factor (VEGF) for growth. Rat eyes were treated with anti-VEGF antibody in the same manner as above; their retinas, harvested shortly thereafter, were added to HUVECs cultured in VEGFcontaining media. The effect of these retinal homogenates on HUVEC proliferation was then assessed. Results: Significant concentrations of IgG1 were detected in the optic nerve (P < 0.001) and retina (P < 0.0001) following topical application. Anti-ICAM-1 antibody also accumulated in the retina after topical application, though levels were less than those seen with IgG1 probably owing to a lower starting concentration. Retinal homogenates from eyes treated with anti-VEGF antibody significantly suppressed HUVEC proliferation (P < 0.0001). Conclusion: Our data support the contention that topically applied antibodies can accumulate in the posterior segment, and suggest they retain their pharmacological properties.

show abstract

Section: Discussionsupporting

confidence: 51%

“…Our previous studies with other peptides suggested the need for this permeation enhancer to facilitate movement through the ocular surface. 24,25 Thus, the final concentration of IgG1 per drop was 22.5 mg/mL.…”

Section: Topical Application Of Igg1mentioning

confidence: 99%

Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration

Koevary

2016

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

show abstract

“…After topical administration of an insulin formulation containing polyoxyethylene-20-stearyl ether as permeation enhancer in rats, insulin accumulated in the retina and optic nerve [82] and was found in the brain and cerebrospinal fluid [83]. Similar results were obtained after ocular administration of a solution containing nerve growth factor.…”

Section: Ocular Administrationmentioning

confidence: 70%

Chitosan Formulations as Carriers for Therapeutic Proteins

Andrade

Antunes²,

Nascimento³

et al. 2011

CDDT

View full text Add to dashboard Cite

Protein drugs represent a significant part of the new pharmaceuticals coming on the market every year and are now widely spread in therapy to treat or relief symptomatology related to many metabolic and oncologic diseases. The delivery of therapeutic proteins is still a major drawback against their maximum pharmacodynamic due to their physicochemical properties, poor stability, permeability and biodistribution. Despite the fact that the parenteral route remains the primary route of protein administration, research continues on non-parenteral delivery routes. However, the high molecular weight of proteins, combined with their hydrophilic and charged nature, renders transport through membranes very difficult. In this regard, the biopolymer chitosan exhibits several favorable biological properties, such as biocompatibility, biodegradability, low-toxicity and mucoadhesiveness, which made it a promising candidate for the formulation of protein drugs. The success of a protein formulation depends not only on the stability of the delivery system but also on their ability to maintain the native structure and activity of the protein during preparation and the delivery, as well as during longterm storage of the formulation. Chitosan-based delivery systems have been proposed as valid approaches to provide such protective conditions. The development of novel protein delivery systems based on chitosan is a rising subject irrespective of the intended route of administration. In this review, the different approaches recently exploited to formulate and deliver therapeutic proteins are underlined.

show abstract

“…In the case of NGF, the combination of two findings, exceptionally high expression of NGF in the eye (Large et al, 1989;Lambiase et al, 2002) and increasing evidence for penetration of small amounts of eyederived proteins such as insulin and NGF into the CSF (Koevary et al, 2003(Koevary et al, , 2004Lambiase et al, 2007), suggest that eye-derived NGF may contribute to the endogenous NGF that is known to be present in the CSF of all vertebrates examined (Xia et al, 2000;Hochhaus et al, 2001;Chiaretti et al, 2008Chiaretti et al, , 2009Mashayekhi et al, 2009). Our study shows that exogenous NGF, when applied intraocularly, gains access to intraventricular CSF spaces.…”

Section: Spillover Of Peptides From the Eye To The Csfmentioning

confidence: 99%

The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes

Feng¹,

Wiggins²,

Bartheld³

2011

Journal of Neuroscience

View full text Add to dashboard Cite

Neurons can access signaling molecules through two principal pathways: synaptic transmission ("wiring transmission") and nonsynaptic transmission ("volume transmission"). Wiring transmission is usually considered the far more important mode of neuronal signaling. Using embryonic chick locus ceruleus (LoC) as a model, we quantified and compared routes of delivery of the neurotrophin nerve growth factor (NGF), either through a multisynaptic axonal pathway or via the CSF. We now show that the axonal pathway from the eye to the LoC involves axo-axonic transfer of NGF with receptor switching (p75 to trkA) in the optic tectum. In addition to the axonal pathway, the LoC of chick embryos has privileged access to the CSF through a specialized glial/ependymal cell type, the tanycyte. The avian LoC internalizes from the CSF in a highly specific fashion both NGF and the hormone urotensin (corticotropin-releasing factor family ligand). Quantitative autoradiography at the ultrastructural level shows that tanycytes transcytose and deliver NGF to LoC neurons via synaptoid contacts. The LoC-associated tanycytes express both p75 and trkA receptors. The NGF extracted by tanycytes from the CSF has physiological effects on LoC neurons, as evidenced by significantly altered nuclear diameters in both gain-of-function and loss-of-function experiments. Quantification of NGF extraction shows that, compared with multisynaptic axonal routes of NGF trafficking to LoC, the tanycyte route is significantly more effective. We conclude that some clinically important neuronal populations such as the LoC can use a highly efficient "back door" interface to the CSF and can receive signals via this tanycyte-controlled pathway.

show abstract

Accumulation of Porcine Insulin in the Rat Brain and Cerebrospinal Fluid Following Ocular Application

Cited by 21 publications

References 22 publications

Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration

Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration

Chitosan Formulations as Carriers for Therapeutic Proteins

The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes

Contact Info

Product

Resources

About