Development of a topical tissue cross-linking solution using sodium hydroxymethylglycinate (SMG): viscosity effect
Jaya Mehta1, Anna Takaoka1, Mariya Zyablitskaya1
1Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, NY.
Bioscience Reports
|December 21, 2019
Summary
Hydroxypropyl methylcellulose (HPMC) enhances the therapeutic cross-linking effect of sodium hydroxymethylglycinate (SMG) in ocular tissues. Higher HPMC concentrations did not impede SMG
Area of Science:
- Ophthalmology
- Biomaterials Science
- Corneal Research
Background:
- Hyperviscosity agents like hydroxypropyl methylcellulose (HPMC) improve drug penetration in ophthalmic formulations by extending tissue contact time.
- HPMC is utilized in riboflavin solutions for photochemical UVA cross-linking (CXL).
- Sodium hydroxymethylglycinate (SMG), a formaldehyde releaser, acts as a therapeutic cross-linker for corneal and scleral tissues.
Purpose of the Study:
- To investigate formulation factors involving HPMC and SMG to enhance cross-linking effects in ocular tissues.
- To evaluate the influence of varying HPMC concentrations on SMG-mediated cross-linking efficacy.
- To assess the impact of HPMC viscosity on the cross-linking of porcine and rabbit corneas and sclera.
Main Methods:
- Formulations with 10 mM SMG and 100 mM sodium bicarbonate were prepared with HPMC concentrations ranging from 0% to 4.4%.
- Cross-linking effects were quantified using differential scanning calorimetry (DSC), measuring the change in melting temperature (ΔTm) compared to controls.
- Ex vivo studies were conducted on porcine and rabbit corneas and sclera.
Main Results:
- SMG in 4.4% HPMC yielded a significant ΔTm of 6.3 ± 1.21 in porcine cornea; other concentrations showed no significant Tm shift.
- A trend of increased cross-linking with higher viscosity was observed in ex vivo rabbit corneas, though differences were mild.
- Significant Tm shifts were noted in porcine and rabbit sclera, with no discernible difference in cross-linking effect across varying HPMC concentrations.
Conclusions:
- Increasing HPMC concentration does not diminish the cross-linking efficacy of SMG in ocular tissues.
- HPMC may act as a beneficial cross-linking enhancer by increasing tissue contact time, crucial for dynamic biological systems.
- Findings support further animal and human studies for optimizing SMG-based ophthalmic formulations.
