Various Approaches Employed to Enhance the Bioavailability of Antagonists Interfering with the HMGB1/RAGE Axis
Abstract
1. Introduction
2. Methodology
3. Various Approaches to Enhance the Solubility/Bioavailability of Synthetic or Natural Molecules
3.1. Nano-Sized Carriers
3.2. Biodegradable Polymers
3.3. Lipid-Based Nanosystems
3.4. Hybrid Approach Combining Polymers and Lipids
3.5. Non-Ionic Surfactants
3.6. Polymer—Surfactant Combinations
4. Drug Molecules Affecting HMGB1/RAGE Axis and Methods to Enhance Their Bioavailability
4.1. Crocin
4.2. Berberine
4.3. Curcumin
4.4. Pentoxifylline
4.5. Doxorubicin/Adriamycin and FPS-ZM1
4.6. Dexmedetomidine
4.7. Epigallocatechin-3-Gallate
4.8. Glycyrrhizin
5. Conclusions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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S No. | Type of Formulation | Year | Patent Number |
---|---|---|---|
1 | Berberine hydrochloride self-microemulsion | 2018 | CN104825389B |
2 | Mangiferin-6-o-berberine salt | 2019 | US10285969B2 |
3 | Extracted from phellodendron amurense | 2019 | CN1100551118B |
4 | Fenofibric acid salt with berberine or its analogs | 2020 | US10577379B10 |
5 | Gelatin-loaded berberine hydrochloride nanoparticles encapsulated by erythrocyte membranes | 2020 | CN108113977B |
6 | Berberine succinate crystals | 2022 | CN115572292A and CN115477647A |
Drugs | Mechanism of Action | Bioavailability Issues | Enhancement Strategies |
---|---|---|---|
Crocin | Suppresses HMGB1/RAGE axis in neuroinflammation | Low bioavailability due to poor absorption and stability | Oral crocin yields higher serum crocetin levels than crocetin itself |
Berberine | Inhibits inflammatory cytokines via HMGB1/RAGE | Very low (<1%) due to poor solubility, metabolism, P-gp efflux | Nanoparticles, self-emulsions, salts, nanocrystals; e.g., 343–404% improved formulations |
Curcumin | Neuroprotection via HMGB1/RAGE; anti-inflammatory agent | Poor solubility, instability, rapid metabolism | Mono-carbonyl analogs, liposomes, micelles, PLGA nanoparticles, PEG, surfactants |
Pentoxifylline | Anti-epileptic via HMGB1/RAGE axis | Low (20–30%) due to poor dissolution rate | Microsponges, solid lipid nanoparticles (SLNs) |
Doxorubicin + FPS-ZM1 | Combination inhibits HMGB1–RAGE in leukemia | Doxorubicin: <5% oral bioavailability; FPS-ZM1: unstable in water | Nanoparticles, liposomes (4–6.8× improvement); use of solvents for FPS-ZM1 |
Dexmedetomidine | Blocks HMGB1 translocation in acute lung injury | Limited data on oral bioavailability | Nasal spray; no significant oral formulation reported |
EGCG | Decreases extracellular HMGB1 and RAGE expression | Low solubility, stability, and permeability; in vivo < in vitro | Nanoparticles, peracetylated EGCG, co-administration with bioactives |
Glycyrrhizin | Inhibits HMGB1–RAGE interaction | Poor oral absorption due to hydrolysis and GI impermeability | Sodium deoxycholate/phospholipid nanomicelles (SDC-PL-MMs), probiotics (L. rhamnosus) |
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Singh, H. Various Approaches Employed to Enhance the Bioavailability of Antagonists Interfering with the HMGB1/RAGE Axis. Int. J. Transl. Med. 2025, 5, 35. https://doi.org/10.3390/ijtm5030035
Singh H. Various Approaches Employed to Enhance the Bioavailability of Antagonists Interfering with the HMGB1/RAGE Axis. International Journal of Translational Medicine. 2025; 5(3):35. https://doi.org/10.3390/ijtm5030035
Chicago/Turabian StyleSingh, Harbinder. 2025. "Various Approaches Employed to Enhance the Bioavailability of Antagonists Interfering with the HMGB1/RAGE Axis" International Journal of Translational Medicine 5, no. 3: 35. https://doi.org/10.3390/ijtm5030035
APA StyleSingh, H. (2025). Various Approaches Employed to Enhance the Bioavailability of Antagonists Interfering with the HMGB1/RAGE Axis. International Journal of Translational Medicine, 5(3), 35. https://doi.org/10.3390/ijtm5030035