Mosawi and Rezaei Niaraki / Advanced formulations of hyaluronic acid and its derivatives for therapeutic applications, 2024,
3(2): 7-13
factor in drug delivery of cancer therapy. In numerous 2290 kDa and concentration of up to 0.1% absorbed
tumor cells, the CD44 receptor, a transmembrane into the purified lanolin and Plastibase® (a
glycoprotein, is highly expressed and regulates hydrocarbon gel ointment) improved re-
metastasis by the migration and invasion processes. epithelialization, the appropriate outcome for healing
These receptors are related to P-glycoprotein 1, chronic wounds. Hyaluronic acid and its derivatives
multidrug resistance protein 1 (MDR1) has three main impact four wound healing steps involving hemostasis,
domains including the intracellular, extracellular inflammation, proliferation, and remodeling. Future
domain, and transmembrane domain [35]. Conjugates studies should focus on overcoming the main side
of nanogel–drugs based on hyaluronic acid- effects of hyaluronic acid gel injection including
membranotropic cholesteryl were utilized to load three infections, tissue necrosis, chronic lymphoplasmacytic
drugs involving curcumin, etoposide, and salinomycin inflammatory reactions, and inadvertent arterial
by negative zeta potential with 6.98, 17.36, and 21.62 occlusion.
% drug content and sizes of 29.15, 32.17, and 36.48 Highlights
nm, respectively. Nanogel–etoposide and nanogel-
salinomycin conjugates displayed values of 3 and 0.9 Study Highlights
μM of half-maximal inhibitory concentration (IC50). In As the bacteriostatic effect, hyaluronic acid can lead
addition, for nanogel-curcumin conjugate, there was 9 to the saturation of the hyaluronidase enzymes of
μM of IC50 more than other hyaluronic acid-based bacteria.
nanogels of etoposide and salinomycin [36]. Carbon- Different molecular weights of hyaluronic acid
based micro- and nanomaterials can be decorated and exhibited different therapeutic effects, specifically
modified by biopolymers such as hyaluronic acid due in the case of the wound healing process.
to upgraded biocompatibility and drug release profile Immobilized hyaluronic acid on PLGA showed
in physiological conditions [37]. Drug carriers with inducing cellular attachment, proliferation, and
pH-responsive property can target cancer cells because differentiation of chondrocytes.
of the low pH environment of tumors. Doxorubicin- Conjugation of oligomers of hyaluronic acid with
loaded graphene oxide was decorated by hyaluronic polymeric hyaluronic acid-aldehyde exhibited
acid to specific target tumor cells. This nanohybrid significant anticancer activity towards cancer HT-29
exhibited the sustained doxorubicin-release in pH 5.3 cells.
and tumor inhibition rate against H22 hepatic cancer in Reducing and overcoming the main side effects of
vivo than graphene oxide–doxorubicin and doxorubicin hyaluronic acid gel injection such as infections and
alone [38]. tissue necrosis should be regarded in future
investigations.
Conclusions
The saturation of the hyaluronidase enzymes as a Abbreviations
virulence factor of bacteria as bacteriostatic activity DFU: Diabetic foot ulcers
can result from hyaluronic acid treatment. As a critical ECM: Extracellular matrix
note, the deferent molecular weight of hyaluronic acid EGF: Epidermal growth factor
leads to different therapeutic effects such as inducing HAS: Hyaluronan synthase
heat shock proteins by 0.4–4.0 kDa, angiogenic (<60 IC50: Half-maximal inhibitory concentration
kDa), wound healing (200–500 kDa), and anti- IL: Interleukin
angiogenic (more than 500 kDa). Bacteriostatic MDR1: Multidrug resistance protein 1
activity for hyaluronic acid is results from the MMP: Matrix metalloproteinase
saturation of the hyaluronidase enzymes of bacteria by MRSA: Methicillin-resistant S. aureus
this biopolymer. Inducing cellular attachment, PLGA: Poly(d,l-lactic acid-co-glycolic acid)
proliferation, and differentiation of chondrocytes has VEGF: Vascular endothelial growth factor
been indicated for immobilized hyaluronic acid on
PLGA. In the case of wound healing activity, Funding
hyaluronic acid with a high molecular weight of up to Any institutes did not support this study.
Micro Nano Bio Aspects 10
Mosawi and Rezaei Niaraki / Advanced formulations of hyaluronic acid and its derivatives for therapeutic applications, 2024, 3(2): 7-13
7. Edwards PC, Fantasia JE. Review of long-term
Funding adverse effects associated with the use of chemically-
Any institutes did not support this study. modified animal and nonanimal source hyaluronic acid
dermal fillers. Clinical Interventions in Aging.
2007;2(4):509-19. doi:https://doi.org/10.2147/cia.s382
Conflict of interest 8. Schanz S, Schippert W, Ulmer A, Rassner G,
The authors declare that they have no conflict of Fierlbeck G. Arterial embolization caused by injection
interest. of hyaluronic acid (Restylane). British Journal of
Dermatology.2002;146(5):928-9.
Ethical approval doi:https://doi.org/10.1046/j.1365-2133.2002.04707.x
This article does not contain any studies with animals 9. Hirsch RJ, Lupo M, Cohen JL, Duffy D. Delayed
presentation of impending necrosis following soft tissue
or human participants performed by any of the authors.
augmentation with hyaluronic acid and successful
management with hyaluronidase. Journal of drugs in
Author contributions dermatology.2007;6(3):325-8.
All authors: conceptualization, preparing the first draft, doi:https://pubmed.ncbi.nlm.nih.gov/17373195/
and editing. 10. Chen X, Zhou J, Qian Y, Zhao L. Antibacterial
coatings on orthopedic implants. Materials Today Bio.
Acknowledgments 2023;19:100586.
doi:https://doi.org/10.1016/j.mtbio.2023.100586
Declared none.
11. Souza JGS, Bertolini MM, Costa RC, Nagay BE,
Dongari-Bagtzoglou A, Barão VAR. Targeting implant-
References associated infections: titanium surface loaded with
1. Prasher P, Sharma M, Mehta M, Satija S, Aljabali AA, antimicrobial. iScience. 2021;24(1):102008.
Tambuwala MM, et al. Current-status and applications doi:https://doi.org/10.1016/j.isci.2020.102008
of polysaccharides in drug delivery systems. Colloid and 12. Ma R, Hu X, Zhang X, Wang W, Sun J, Su Z, et al.
Interface Science Communications. 2021;42:100418. Strategies to prevent, curb and eliminate biofilm
doi:https://doi.org/10.1016/j.colcom.2021.100418 formation based on the characteristics of various periods
2. Zamboni F, Wong CK, Collins MN. Hyaluronic acid in one biofilm life cycle. Frontiers in Cellular and
association with bacterial, fungal and viral infections: Infection Microbiology. 2022;12.
Can hyaluronic acid be used as an antimicrobial doi:https://doi.org/10.3389/fcimb.2022.1003033
polymer for biomedical and pharmaceutical 13. Khatoon Z, McTiernan CD, Suuronen EJ, Mah T-F,
applications? Bioactive Materials. 2023;19:458-73. Alarcon EI. Bacterial biofilm formation on implantable
doi:https://doi.org/10.1016/j.bioactmat.2022.04.023 devices and approaches to its treatment and prevention.
3. Graciela C-Q, José Juan E-C, Gieraldin C-L, Xóchitl Heliyon.2018;4(12).
Alejandra P-M, Gabriel A-Á. Hyaluronic doi:https://doi.org/10.1016/j.heliyon.2018.e01067
Acid—Extraction Methods, Sources and 14. Mohan Agarwal K, Singhal A, Kapoor A, Bhatia D.
Applications. Polymers. 2023;15(16):3473. Simulated analysis of Ti-6Al-4V processed through
doi:https://doi.org/10.3390/polym15163473 equal channel angular pressing for biomedical
4. Sodhi H, Panitch A. Glycosaminoglycans in Tissue applications. Materials Science for Energy
Engineering: A Review. Biomolecules. 2021;11(1):29. Technologies.2021;4:290-5.
doi:https://doi.org/10.3390/biom11010029 doi:https://doi.org/10.1016/j.mset.2021.08.005
5. Saravanakumar K, Park S, Santosh SS, 15. Shende P, Patil A, Prabhakar B. Layer-by-layer
Ganeshalingam A, Thiripuranathar G, Sathiyaseelan A, technique for enhancing physicochemical properties of
et al. Application of hyaluronic acid in tissue actives. Journal of Drug Delivery Science and
engineering, regenerative medicine, and nanomedicine: Technology.2020;56:101519.
A review. International Journal of Biological doi:https://doi.org/10.1016/j.jddst.2020.101519
Macromolecules.2022;222:2744-60. 16. Valverde A, Pérez-Álvarez L, Ruiz-Rubio L, Pacha
doi:https://doi.org/10.1016/j.ijbiomac.2022.10.055 Olivenza MA, García Blanco MB, Díaz-Fuentes M, et
6. Snetkov P, Zakharova K, Morozkina S, Olekhnovich al. Antibacterial hyaluronic acid/chitosan multilayers
R, Uspenskaya M. Hyaluronic Acid: The Influence of onto smooth and micropatterned titanium surfaces.
Molecular Weight on Structural, Physical, Physico- Carbohydrate Polymers. 2019;207:824-33.
Chemical, and Degradable Properties of Biopolymer. doi:https://doi.org/10.1016/j.carbpol.2018.12.039
Polymers.2020;12(8):1800. 17. Andrade del Olmo J, Alonso JM, Sáez-Martínez V,
doi:https://doi.org/10.3390/polym12081800 Benito-Cid S, Pérez-González R, Vilas-Vilela JL, et al.
Micro Nano Bio Aspects 11
