Molecular and Cellular Studies of Hyaluronic Acid-Modified Liposomes as Bioadhesive Carriers for Topical Drug Delivery in Wound Healing

Yerushalmi, Noga; Arad, Aya; Margalit, Rimona

doi:10.1006/abbi.1994.1387

Cited by 94 publications

(81 citation statements)

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“…The presence of HA and PL complexes could provide excellent protection of the cartilage surface from enzymes and free radicals in the synovial fluid, so it could be used as an oral protectant of joint function [18] . HA is a slow-release carrier due to its bioadhesion and biocompatibility properties [19] . After the formation of complex, HA could improve the absorption of PL because of the three dimensions network of HA, and enhance the health care effect of PL.…”

Section: Discussionmentioning

confidence: 99%

Oral absorption of hyaluronic acid and phospholipids complexes in rats

Huang¹

2007

WJG

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AIM:To prepare a complex of hyaluronic acid (HA) and phospholipids (PL), and study the improvement effect of PL on the oral absorption of HA. METHODS:The complex of HA-PL (named Haplex) was prepared by film dispersion and sonication method, its physico-chemical properties were identified by infrared spectra and differential scanning calorimetry (DSC). The oral absorption of Haplex was studied. Thirty-two healthy rats were divided into 4 groups randomly: (1) a normal saline (NS) control group; (2) an HA group; (3) a mixture group and (4) a Haplex group. After intragastric administration, the concentration of HA in serum was determined. RESULTS:The physico-chemical properties of Haplex were different from HA or PL or their mixture. After Haplex was administered to rats orally, the serum concentration of HA was increased when compared with the mixture or HA control groups from 4 h to 10 h (P < 0.05). The ∆AUC0-12 h of Haplex was also greater than that of the other three groups (P < 0.05). CONCLUSION:The method of film dispersion and sonication can prepare HA and PL complex, and PL can enhance the oral absorption of exogenous HA.© 2007 The WJG Press. All rights reserved.Key words: Hyaluronic acid; Phospholipids; Complex; Oral absorption; Infrared spectrum; Thermochemistry H u a n g S L , L i n g P X , Z h a n g T M . O ra l a b s o r p t i o n o f hyaluronic acid and phospholipids complexes in rat. World J Gastroenterol 2007; 13(6): 945-949

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Section: Discussionmentioning

confidence: 99%

Oral absorption of hyaluronic acid and phospholipids complexes in rats

Huang¹

2007

WJG

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“…37,38,41,69,70 Two different approaches to attach HA to liposomes were developed. 41,75 In the earliest report, HMW-HA was coupled via the glucuronic carboxylate to phosphatidylethanolamine in pre-formed liposomes. 75 This coupling method results in multipoint attachment of the HA to a liposome.…”

Section: C Hyaluronan In a Targeted Nanocarrier Systemmentioning

confidence: 99%

“…41,75 In the earliest report, HMW-HA was coupled via the glucuronic carboxylate to phosphatidylethanolamine in pre-formed liposomes. 75 This coupling method results in multipoint attachment of the HA to a liposome. The number and distribution of the resulting attachment points was difficult to characterize.…”

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confidence: 99%

Anticancer Therapeutics: Targeting Macromolecules and Nanocarriers to Hyaluronan or CD44, a Hyaluronan Receptor

2008

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The complex system involved in the synthesis, degradation, and binding of the high molecular weight glycosaminoglycan hyaluronic acid (hyaluronan or HA) provides a variety of structures that can be exploited for targeted cancer therapy. In many cancers of epithelial origin there is an up-regulation of CD44, a receptor that binds HA. In other cancers, HA in the tumor matrix is over-expressed. Both CD44 on cancer cells and HA in the matrix have been targets for anti-cancer therapy. Even though CD44 is expressed in normal epithelial cells and HA is part of the matrix of normal tissues, selective targeting to cancer is possible. This is because macromolecular carriers predominantly extravasate into the tumor and not normal tissue; thus CD44-HA targeted carriers administered intravenously localize preferentially into tumors. Anti-CD44 antibodies have been used in patients to deliver radioisotopes or mertansine for treatment of CD44 expressing tumors. In early phase clinical trials, patients with breast or head and neck tumors treated with anti-CD44 conjugates experienced stabilized disease. A dose-limiting toxicity was associated with distribution of the antibody-drug conjugate to the skin, a site in the body with a high level of CD44. HA has been used as a drug carrier and a ligand on liposomes or nanoparticles to target drugs to CD44 over-expressing cells. Drugs can be attached to HA via the carboxylate on the glucuronic acid residue, the hydroxyl on the Nacetylglucosamine, or the reducing end which are located on a repeating disaccharide. Drugs delivered in HA-modified liposomes exhibited excellent anti-tumor activity both in vitro and in murine tumor models. The HA matrix is also a potential target for anti-cancer therapies. By manipulating the interaction of HA with cell surface receptors, either by degrading it with hyaluronidase or by interfering with CD44-HA interactions using soluble CD44 proteins, tumor progression was blocked. Finally, cytotoxic drugs or pro-drug converting enzymes can be attached to the HA matrix to generate a cytotoxic fence around the tumor. This review describes how the complex interplay among cancer biology, the CD44-HA interaction, drug carriers and drug targeting has been used to improve anti-cancer therapies. As these approaches evolve, they hold forth the prospect of significantly improved targeted anti-cancer treatments. KeywordsAntibody; Biodistribution; Cancer; Chemotherapy; Drug-conjugate; EPR effect; Liposome; Polymer; Prodrug; Recombinant Protein The Biology of the CD44-Hyaluronan InteractionHyaluronan (HA) (Figure 1) is a high molecular weight glycosaminoglycan, extracellular matrix component essential for proper cell growth, organ structural stability, and tissue organization. The amount of HA in a tissue depends upon on a complex interplay among HA synthesis by HA synthases, 1 HA internalization by cell surface receptors, 2 Interference with the CD44-HA interaction by either targeting drugs to CD44, 14 targeting drugs to the HA matrix 15 or interfering with HA ma...

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“…Epidermal-growth-factor-loaded liposomes anchored with HA on the surface suggested HA to act as site-adherent and sustained-release carrier of drugs for the topical therapy of wounds and burns [50]. In this early study, epidermal growth factor served as a test drug and a human epidermoid carcinoma cell line as model of an in vivo target.…”

Section: Drug Deliverymentioning

confidence: 99%

Hyaluronic Acid in the Treatment and Prevention of Skin Diseases: Molecular Biological, Pharmaceutical and Clinical Aspects

Weindl

Schaller²,

Schäfer‐Korting³

et al. 2004

Skin Pharmacol Physiol

163

128

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The glycosaminoglycan hyaluronic acid (HA), or hyaluronan, is a major component of the extracellular matrix of skin, joints, eye and many other tissues and organs. In spite of its simple structure, HA demonstrates remarkable rheological, viscoelastic and hygroscopic properties which are relevant for dermal tissue function. Biological activities in skin, however, are also due to its interaction with various binding proteins (hyaladherins). Due to an influence on signaling pathways, HA is involved in the wound-healing process and scarless fetal healing. Increased HA concentrations have been associated with inflammatory skin diseases. In clinical trials, topical application of HA improved wound healing; in particular, acute radioepithelitis, venous leg ulcers or diabetic foot lesions responded to HA treatment. Moreover, as a topical drug delivery system for diclofenac, an HA gel has recently been approved for the treatment of actinic keratoses. Finally, chemical modifications led to new HA derivates and biomaterials, which may be introduced into therapy in the future. Therefore, ongoing research offers new horizons for the therapeutic use of this glycosaminoglycan which has been regarded as an inert structural component until recently.

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Molecular and Cellular Studies of Hyaluronic Acid-Modified Liposomes as Bioadhesive Carriers for Topical Drug Delivery in Wound Healing

Cited by 94 publications

References 0 publications

Oral absorption of hyaluronic acid and phospholipids complexes in rats

Oral absorption of hyaluronic acid and phospholipids complexes in rats

Anticancer Therapeutics: Targeting Macromolecules and Nanocarriers to Hyaluronan or CD44, a Hyaluronan Receptor

Hyaluronic Acid in the Treatment and Prevention of Skin Diseases: Molecular Biological, Pharmaceutical and Clinical Aspects

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