Skip to main content
SpringerLink
Log in

Hyaluronic Acid for Percutaneous Drug Delivery

  • Chapter
Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement

  • 1835 Accesses

Abstract

Hyaluronic acid, a high-molecular-weight biopolymer, is of special interest as carrier material in drug delivery due to its biocompatibility, biodegradability, special viscoelastic properties, as well as its ability to create a dense network in which drugs might be incorporated. Hyaluronic acid has a broad applicability in various conditions such as in cosmetic products in terms of anti-wrinkle treatment and skin hydration, local drug delivery, intra-articular injection into arthritic joints and visco-supplementation in ophthalmology.

This chapter focuses on the use of hyaluronic acid-based formulations in cosmetics as well as for intra-/transdermal delivery of drugs. We elucidate the role of hyaluronic acid/fragments as a skin penetration enhancer and tried to highlight the properties of hyaluronic acid which make them unique in the field of drug delivery.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alam CA, Seed MP, Willoughby DA (1995) Angiostasis and vascular regression in chronic granulomatous inflammation induced by diclofenac in combination with hyaluronan in mice. J Pharm Pharmacol 47(5):407–411

    Article  CAS  PubMed  Google Scholar 

  • Barnes L, Tran C, Sorg O, Hotz R, Grand D, Carraux P et al (2010) Synergistic effect of hyaluronate fragments in retinaldehyde-induced skin hyperplasia which is a Cd44-dependent phenomenon. PLoS One 5(12), e14372

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Birkenfeld B, Parafiniuk M, Bielecka-Grzela S, Klimowicz A, Piwowarska-Bilska H, Mikolajczak R et al (2011) The penetration of topically applied ointment containing hyaluronic acid in rabbit tissues. Pol J Vet Sci 14(4):621–627

    CAS  PubMed  Google Scholar 

  • Boateng JS, Matthews KH, Stevens HN, Eccleston GM (2008) Wound healing dressings and drug delivery systems: a review. J Pharm Sci 97(8):2892–2923

    Article  CAS  PubMed  Google Scholar 

  • Bourguignon LY, Singleton PA, Diedrich F (2004) Hyaluronan-CD44 interaction with Rac1-dependent protein kinase N-gamma promotes phospholipase Cgamma1 activation, Ca(2+) signaling, and cortactin-cytoskeleton function leading to keratinocyte adhesion and differentiation. J Biol Chem 279(28):29654–29669

    Google Scholar 

  • Brown MB, Hanpanitcharoen M, Martin GP (2001) An in vitro investigation into the effect of glycosaminoglycans on the skin partitioning and deposition of NSAIDs. Int J Pharm 225(1-2):113–121

    Article  CAS  PubMed  Google Scholar 

  • Brown MB, Jones SA (2005) Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin. J Eur Acad Dermatol Venereol 19(3):308–318

    Google Scholar 

  • Brown MB, Marriott C, Martin GP (1995) The effect of hyaluronan on the in vitro deposition of diclofenac within the skin. Int J Tissue React 17(4):133–140

    CAS  PubMed  Google Scholar 

  • Brown TJ, Alcorn D, Fraser JR (1999) Absorption of hyaluronan applied to the surface of intact skin. J Invest Dermatol 113(5):740–746

    Article  CAS  PubMed  Google Scholar 

  • Chen WY, Marcellin E, Hung J, Nielsen LK (2009) Hyaluronan molecular weight is controlled by UDP-N-acetylglucosamine concentration in Streptococcus zooepidemicus. J Biol Chem 284(27):18007–18014

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Colletta V, Dioguardi D, Di Lonardo A, Maggio G, Torasso F (2003) A trial to assess the efficacy and tolerability of Hyalofill-F in non-healing venous leg ulcers. J Wound Care 12(9):357–360

    Article  CAS  PubMed  Google Scholar 

  • Cordero A, Leon-Dorantes G, Pons-Guiraud A, Di Pietro A, Asensi SV, Walkiewicz-Cyraska B et al (2011) Retinaldehyde/hyaluronic acid fragments: a synergistic association for the management of skin aging. J Cosmet Dermatol 10(2):110–117

    Article  PubMed  Google Scholar 

  • Costagliola M, Agrosi M (2005) Second-degree burns: a comparative, multicenter, randomized trial of hyaluronic acid plus silver sulfadiazine vs. silver sulfadiazine alone. Curr Med Res Opin 21(8):1235–1240

    Article  CAS  PubMed  Google Scholar 

  • Dusio GF, Cardani D, Zanobbio L, Mantovani M, Luchini P, Battini L et al (2011) Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium. Immunol Cell Biol 89(5):630–639

    Article  CAS  PubMed  Google Scholar 

  • Farwick M, Gauglitz G, Pavicic T, Kohler T, Wegmann M, Schwach-Abdellaoui K et al (2011) Fifty-kDa hyaluronic acid upregulates some epidermal genes without changing TNF-alpha expression in reconstituted epidermis. Skin Pharmacol Physiol 24(4):210–217

    Article  CAS  PubMed  Google Scholar 

  • Gao F, Liu Y, He Y, Yang C, Wang Y, Shi X et al (2010) Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis. Matrix Biol 29(2):107–116

    Article  CAS  PubMed  Google Scholar 

  • Greco RM, Iocono JA, Ehrlich HP (1998) Hyaluronic acid stimulates human fibroblast proliferation within a collagen matrix. J Cell Physiol 177(3):465–473

    Google Scholar 

  • Hall CL, Wang C, Lange LA, Turley EA (1994) Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity. J Cell Biol 126(2):575–588

    Article  CAS  PubMed  Google Scholar 

  • Ito Y, Kashiwara S, Fukushima K, Takada K (2011) Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats. Drug Dev Ind Pharm 37(12):1387–1393

    Article  CAS  PubMed  Google Scholar 

  • Jarvis B, Figgitt DP (2003) Topical 3% diclofenac in 2.5% hyaluronic acid gel: a review of its use in patients with actinic keratoses. Am J Clin Dermatol 4(3):203–213

    Article  PubMed  Google Scholar 

  • Jiskoot W, Randolph TW, Volkin DB, Middaugh CR, Schoneich C, Winter G et al (2012) Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release. J Pharm Sci 101(3):946–954

    Article  CAS  PubMed  Google Scholar 

  • Kaya G, Tran C, Sorg O, Hotz R, Grand D, Carraux P et al (2006) Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism. PLoS Med 3(12), e493

    Article  PubMed Central  PubMed  Google Scholar 

  • Kogan G, Soltes L, Stern R, Gemeiner P (2007) Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol Lett 29(1):17–25

    Article  CAS  PubMed  Google Scholar 

  • Koller J (2004) Topical treatment of partial thickness burns by silver sulfadiazine plus hyaluronic acid compared to silver sulfadiazine alone: a double-blind, clinical study. Drugs Exp Clin Res 30(5-6):183–190

    CAS  PubMed  Google Scholar 

  • Lai ZW, Rahim RA, Ariff AB, Mohamad R (2012) Biosynthesis of high molecular weight hyaluronic acid by Streptococcus zooepidemicus using oxygen vector and optimum impeller tip speed. J Biosci Bioeng 114(3):286–291

    Article  CAS  PubMed  Google Scholar 

  • Lapcik L Jr, Lapcik L, De Smedt S, Demeester J, Chabrecek P (1998) Hyaluronan: preparation, structure, properties, and applications. Chem Rev 98(8):2663–2684

    Article  CAS  PubMed  Google Scholar 

  • Liguori V, Guillemin C, Pesce GF, Mirimanoff RO, Bernier J (1997) Double-blind, randomized clinical study comparing hyaluronic acid cream to placebo in patients treated with radiotherapy. Radiother Oncol 42(2):155–161

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Jin MN, Quan YS, Kamiyama F, Katsumi H, Sakane T et al (2012) The development and characteristics of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of insulin. J Control Release 161(3):933–941

    Article  CAS  PubMed  Google Scholar 

  • Lyons RT, Robinson MR, Trogden JT, Whitcup SM, inventors (2008) Peripherally administered viscous formulations. US 20140356438 A1

    Google Scholar 

  • Meyer J, Whitcomb L, Treuheit M, Collins D (1995) Sustained in vivo activity of recombinant human granulocyte colony stimulating factor (rHG-CSF) incorporated into hyaluronan. J Control Release 35:67–72

    Article  CAS  Google Scholar 

  • Milas M, Rinaudo M (2005) Characterization and properties of hyaluronic acid (hyaluronan). In: Dumitriu S (ed) Polysaccharides: structural diversity and functional versatility. Marcel Dekker, New York, pp 535–549

    Google Scholar 

  • Mohapatra S, Yang X, Wright JA, Turley EA, Greenberg AH (1996) Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression. J Exp Med 183(4):1663–1668

    Article  CAS  PubMed  Google Scholar 

  • Moseley R, Walker M, Waddington RJ, Chen WY (2003) Comparison of the antioxidant properties of wound dressing materials--carboxymethylcellulose, hyaluronan benzyl ester and hyaluronan, towards polymorphonuclear leukocyte-derived reactive oxygen species. Biomaterials 24(9):1549–1557

    Article  CAS  PubMed  Google Scholar 

  • Necas J, Bartosikova L, Brauner P, Kolar J (2008) Hyaluronic acid (hyaluronan): a review. Vet Med 53:397–411

    CAS  Google Scholar 

  • Ortonne JP (2001) [Comparative study of the activity of hyaluronic acid and dextranomer in the treatment of leg ulcers of venous origin]. Annales de dermatologie et de venereologie (Suppl):13–16

    Google Scholar 

  • Pavicic T, Gauglitz GG, Lersch P, Schwach-Abdellaoui K, Malle B, Korting HC et al (2011) Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol 10(9):990–1000

    CAS  PubMed  Google Scholar 

  • Price RD, Berry MG, Navsaria HA (2007) Hyaluronic acid: the scientific and clinical evidence. J Plast Reconstr Aesthet Surg 60(10):1110–1119

    Article  PubMed  Google Scholar 

  • Prisell PT, Camber O, Hiselius J, Norstedt G (1992) Evaluation of hyaluronan as a vehicle for peptide growth factors. Int J Pharm 85:51–60

    Article  CAS  Google Scholar 

  • Rossi S, Marciello M, Sandri G, Ferrari F, Bonferoni MC, Papetti A et al (2007) Wound dressings based on chitosans and hyaluronic acid for the release of chlorhexidine diacetate in skin ulcer therapy. Pharm Dev Technol 12(4):415–422

    Article  CAS  PubMed  Google Scholar 

  • Rossler A, Hinghofer-Szalkay H (2003) Hyaluronan fragments: an information-carrying system? Horm Metab Res 35(2):67–68

    Article  CAS  PubMed  Google Scholar 

  • Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85(8):699–715

    Article  CAS  PubMed  Google Scholar 

  • Stern R, Kogan G, Jedrzejas MJ, Soltes L (2007) The many ways to cleave hyaluronan. Biotechnol Adv 25(6):537–557

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, inventor (2004) Pharmaceutical composition containing viscoelastic substance and medication. US 20040038936 A1

    Google Scholar 

  • Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL (2004) Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem 279(17):17079–17084

    Article  CAS  PubMed  Google Scholar 

  • Trommer H, Wartewig S, Bottcher R, Poppl A, Hoentsch J, Ozegowski JH et al (2003) The effects of hyaluronan and its fragments on lipid models exposed to UV irradiation. Int J Pharm 254(2):223–234

    Article  CAS  PubMed  Google Scholar 

  • Vazquez JR, Short B, Findlow AH, Nixon BP, Boulton AJ, Armstrong DG (2003) Outcomes of hyaluronan therapy in diabetic foot wounds. Diabetes Res Clin Pract 59(2):123–127

    Article  CAS  PubMed  Google Scholar 

  • Voelcker V, Gebhardt C, Averbeck M, Saalbach A, Wolf V, Weih F et al (2008) Hyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signalling via TLR4. Exp Dermatol 17(2):100–107

    Article  CAS  PubMed  Google Scholar 

  • Voinchet V, Vasseur P, Kern J (2006) Efficacy and safety of hyaluronic acid in the management of acute wounds. Am J Clin Dermatol 7(6):353–357

    Article  PubMed  Google Scholar 

  • Weindl G, Schaller M, Schafer-Korting M, Korting HC (2004) Hyaluronic acid in the treatment and prevention of skin diseases: molecular biological, pharmaceutical and clinical aspects. Skin Pharmacol Physiol 17(5):207–213

    Article  CAS  PubMed  Google Scholar 

  • Witting M, Boreham A, Brodwolf R, Vávrová K, Alexiev U, Friess W et al (2015) Interactions of hyaluronic Acid with the skin and implications for the dermal delivery of biomacromolecules. Mol Pharm. 12(5):1391–401

    Google Scholar 

  • Xie Y, Upton Z, Richards S, Rizzi SC, Leavesley DI (2011) Hyaluronic acid: evaluation as a potential delivery vehicle for vitronectin: growth factor complexes in wound healing applications. J Control Release 153(3):225–232

    Article  CAS  PubMed  Google Scholar 

  • Yang JA, Kim ES, Kwon JH, Kim H, Shin JH, Yun SH et al (2012) Transdermal delivery of hyaluronic acid – human growth hormone conjugate. Biomaterials 33(25):5947–5954

    Article  CAS  PubMed  Google Scholar 

  • Zavan B, Vindigni V, Vezzu K, Zorzato G, Luni C, Abatangelo G et al (2009) Hyaluronan based porous nano-particles enriched with growth factors for the treatment of ulcers: a placebo-controlled study. J Mater Sci Mater Med 20(1):235–247

    Article  CAS  PubMed  Google Scholar 

  • Zhang LS, Greyner HJ, Mummert ME, Petroll WM (2009) Development of a hyaluronan bioconjugate for the topical treatment of melanoma. J Dermatol Sci 55(1):56–59

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Königin-Luise-Str. 2-4, Berlin, 14195, Germany

    Sarah Hedtrich

  2. Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität, Munich, Germany

    Wolfgang Frieß

Authors
  1. Sarah Hedtrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Frieß
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah Hedtrich .

Editor information

Editors and Affiliations

  1. Department of Manufacturing, Apoteka "Beograd", Belgrade, Serbia

    Nina Dragicevic

  2. Dermatology Clinic, University of California San Francisco Dermatology Clinic, San Francisco, USA

    Howard I. Maibach

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hedtrich, S., Frieß, W. (2015). Hyaluronic Acid for Percutaneous Drug Delivery. In: Dragicevic, N., Maibach, H. (eds) Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-47039-8_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-47039-8_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-47038-1

  • Online ISBN: 978-3-662-47039-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation