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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Engineered hyalurosomal gel co-delivering citicoline sodium and nifedipine for potential glaucoma management: formulation and pharmacodynamic evaluation

  • Doaa Hegazy1
  • Mennatullah M. Ibrahim1
  • Riham A. El-Shiekh2
  • Osama Saher1,3,4
  • Nouran A. Ali1
4 affiliations
  1. 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University
  2. 2Department of Pharmacognosy, Faculty of Pharmacy, Cairo University
  3. 3Department of Laboratory Medicine, Karolinska Institute
  4. 4Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center
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Abstract

Introduction: Glaucoma is a neurodegenerative ocular disorder that requires multi-targeted therapeutic strategies to counteract intraocular pressure (IOP) elevation and oxidative stress–mediated retinal ganglion cells (RGCs) loss. This study developed an innovative hyalurosomal hydrogel platform co-delivering Nifedipine (NFD, a calcium channel blocker that promotes ocular vasodilation and IOP reduction) and Citicoline sodium (CTC, a potent neuroprotective and antioxidant agent) as a potential topical therapeutic approach for glaucoma.

Methods: NFD-loaded hyalurosomes (NFD-HAs) were prepared using thin-film hydration and statistically optimized via a D-Optimal design. The optimized formulation (NFD-OF) was probe-sonicated, combined with CTC, and incorporated into an HPMC hydrogel.

Results and discussion: Sonicated NFD-OF displayed nanosized spherical vesicles (198.6 ± 23.1 nm), high entrapment efficiency (70.7 ± 1.8%), and stable zeta potential (–39.1 ± 1.3 mV). Transmission electron microscopy (TEM) analysis confirmed the distinct spherical morphology, non-aggregated state, and structural integrity of NFD-OF. The final CTC/NFD-OF gel exhibited pseudoplastic shear-thinning flow, an optimal ocular pH (6.9 ± 0.02), and sustained release over 24 h (65.5% for NFD and 99.5% for CTC). The dual gel demonstrated superior free radical scavenging capability (IC ₅₀ = 16.44±0.7 μg/mL) compared to free NFD (219.43 μg/mL) and CTC (234.62 μg/mL). Confocal microscopy confirmed a 2.2-fold enhancement in transcorneal penetration depth (110 μm) compared with the control solution (50 μm). In vivo pharmacodynamic evaluation revealed a significantly higher maximum IOP decrease (51.85 ± 8.2%), extended mean residence time (8.9 ± 2.7 h), and increased relative exposure (AUC ₀ –∞ = 494.1 ± 191.9) compared to commercial Xola™ eye drops (36.4 ± 5.9% max IOP decrease, AUC ₀ –∞ = 182.8 ± 33.7). Terminal gamma sterilization preserved physicochemical characteristics and release profiles. Draize and histopathological assays confirmed excellent ocular tolerability. Overall, the CTC/NFD-OF gel demonstrated promising ocular hypotensive activity and safety, supporting its potential as a multifunctional topical therapeutic approach for glaucoma.

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Cite

BibTeXRIS
BibTeX
@article{hegazy2026engineered,
  title = {{Engineered hyalurosomal gel co-delivering citicoline sodium and nifedipine for potential glaucoma management: formulation and pharmacodynamic evaluation}},
  author = {Doaa Hegazy and Mennatullah M. Ibrahim and Riham A. El-Shiekh and Osama Saher and Nouran A. Ali},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1977895},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1977895/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Engineered hyalurosomal gel co-delivering citicoline sodium and nifedipine for potential glaucoma management: formulation and pharmacodynamic evaluation
AU  - Doaa Hegazy
AU  - Mennatullah M. Ibrahim
AU  - Riham A. El-Shiekh
AU  - Osama Saher
AU  - Nouran A. Ali
PY  - 2026
DA  - 2026/10/23
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1977895
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1977895/full
AB  - Introduction: Glaucoma is a neurodegenerative ocular disorder that requires multi-targeted therapeutic strategies to counteract intraocular pressure (IOP) elevation and oxidative stress–mediated retinal ganglion cells (RGCs) loss. This study developed an innovative hyalurosomal hydrogel platform co-delivering Nifedipine (NFD, a calcium channel blocker that promotes ocular vasodilation and IOP reduction) and Citicoline sodium (CTC, a potent neuroprotective and antioxidant agent) as a potential topical therapeutic approach for glaucoma.  Methods: NFD-loaded hyalurosomes (NFD-HAs) were prepared using thin-film hydration and statistically optimized via a D-Optimal design. The optimized formulation (NFD-OF) was probe-sonicated, combined with CTC, and incorporated into an HPMC hydrogel.  Results and discussion: Sonicated NFD-OF displayed nanosized spherical vesicles (198.6 ± 23.1 nm), high entrapment efficiency (70.7 ± 1.8%), and stable zeta potential (–39.1 ± 1.3 mV). Transmission electron microscopy (TEM) analysis confirmed the distinct spherical morphology, non-aggregated state, and structural integrity of NFD-OF. The final CTC/NFD-OF gel exhibited pseudoplastic shear-thinning flow, an optimal ocular pH (6.9 ± 0.02), and sustained release over 24 h (65.5% for NFD and 99.5% for CTC). The dual gel demonstrated superior free radical scavenging capability (IC ₅₀ = 16.44±0.7 μg/mL) compared to free NFD (219.43 μg/mL) and CTC (234.62 μg/mL). Confocal microscopy confirmed a 2.2-fold enhancement in transcorneal penetration depth (110 μm) compared with the control solution (50 μm). In vivo pharmacodynamic evaluation revealed a significantly higher maximum IOP decrease (51.85 ± 8.2%), extended mean residence time (8.9 ± 2.7 h), and increased relative exposure (AUC ₀ –∞ = 494.1 ± 191.9) compared to commercial Xola™ eye drops (36.4 ± 5.9% max IOP decrease, AUC ₀ –∞ = 182.8 ± 33.7). Terminal gamma sterilization preserved physicochemical characteristics and release profiles. Draize and histopathological assays confirmed excellent ocular tolerability. Overall, the CTC/NFD-OF gel demonstrated promising ocular hypotensive activity and safety, supporting its potential as a multifunctional topical therapeutic approach for glaucoma.
SN  - 1663-9812
ER  -