+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for ocular drug delivery



A stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for ocular drug delivery



Drug Delivery and Translational Research 8(3): 484-495



Most medications targeting optic neuropathies are administered as eye drops. However, their corneal penetration efficiencies are typically < 5%. There is a clear, unmet need for novel transcorneal drug delivery vehicles. To this end, we have developed a stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for controlled release of poorly bioavailable drugs into the aqueous humor of the eye. The hydrogel is formulated as a composite of hyaluronic acid (HA) and methylcellulose (MC). The amphiphilic nanoparticles are composed of poly(ethylene oxide) (PEO) and poly(lactic acid) (PLA). Experimental design aided the identification of hydrogel composition and nanoparticle content in the formulation, and the formulation reliably switched between thixotropy and temperature-dependent rheopexy when it was tested in a rheometer under conditions that simulate the ocular surface, including blinking. These properties should ensure that the formulation coats the cornea through blinking of the eyelid and facilitate application of the medication as an eye drop immediately prior to the patient's bedtime. We subsequently tested the efficacy of our formulation in whole-eye experiments by loading the nanoparticles with cannabigerolic acid (CBGA). Our formulation exhibits over a 300% increase in transcorneal penetration over control formulations. This work paves the way for the introduction of novel products targeting ocular diseases to the market.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051309245

Download citation: RISBibTeXText

PMID: 29508159

DOI: 10.1007/s13346-018-0504-x


Related references

Recent advance technique for ocular drug delivery by Gupta et al.: Nanoparticle laden in situ gel. Journal of Pharmacy and Bioallied Sciences 5(3): 175, 2013

Stimulus-Responsive Hydrogel for Ophthalmic Drug Delivery. Macromolecular Bioscience 19(6): E1900001, 2019

Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel. Part 2: sol-gel-sol transition and drug delivery behavior. Acta Biomaterialia 5(9): 3358-3370, 2009

Nanoparticles laden in situ gel for sustained ocular drug delivery. Journal of Pharmacy and Bioallied Sciences 5(2): 162-165, 2013

In situ-forming and pH-responsive hydrogel based on chitosan for vaginal delivery of therapeutic agents. Journal of Materials Science. Materials in Medicine 29(11): 158, 2018

Novel in situ forming hydrogel microneedles for transdermal drug delivery. Drug Delivery and Translational Research 7(1): 16-26, 2017

Nanoparticle-loaded biodegradable light-responsive in situ forming injectable implants for effective peptide delivery to the posterior segment of the eye. Medical Hypotheses 103: 5-9, 2017

Hydrogel-Forming Microneedle Arrays Made from Light-Responsive Materials for On-Demand Transdermal Drug Delivery. Molecular Pharmaceutics 13(3): 907-914, 2016

Microneedle-mediated intrascleral delivery of in situ forming thermoresponsive implants for sustained ocular drug delivery. Journal of Pharmacy and Pharmacology 66(4): 584-595, 2014

Studies on In situ Hydrogel: A Smart Way for Safe and Sustained Ocular Drug Delivery. Journal of Young Pharmacists 2(2): 116-120, 2010

In situ covalently cross-linked PEG hydrogel for ocular drug delivery applications. International Journal of Pharmaceutics 470(1-2): 151-157, 2014

Novel in situ forming hydrogel based on xanthan and chitosan re-gelifying in liquids for local drug delivery. Carbohydrate Polymers 186: 54-63, 2018

Multifunctional poly(β-amino ester) hydrogel microparticles in periodontal in situ forming drug delivery systems. Biomedical Materials 11(2): 025002, 2016

Thermosensitive PEG-PCL-PEG (PECE) hydrogel as an in situ gelling system for ocular drug delivery of diclofenac sodium. Drug Delivery 23(1): 63-68, 2016

A novel poloxamers/hyaluronic acid in situ forming hydrogel for drug delivery: rheological, mucoadhesive and in vitro release properties. European Journal of Pharmaceutics and Biopharmaceutics 70(1): 199-206, 2008