Formulations Using Hyaluronan

Drug Formulations Using Hyaiuronan A. Hyaluronan/Drug Admixtures in Oncology 

Particular interest has also been devoted to HA as a potential delivery vehicle for 

HA has been shown to produce synergistic therapeutic effects when coadministered with 5-fluorouracil (5-FU) and with PTX. HA formulated with 5-FU enhanced the cellular uptake and cytotoxicity of the drug compared to unformulated 5-FU (98). A similar effect has been observed when PTX was coadministered with HA (99). The admixture of PTX and HA significantly reduced the migration of Lewis lung carcinoma cells in a synergistic fashion and markedly improved the life span of mice seeded with tumor cells compared with PTX alone or HA alone. 

Hyaluronan-Mediated Enhanced Transdermal Delivery of Chemotherapeutics 

Hydration is the most widely used and safest method to increase skin penetration of both hydrophilic and lipophilic permeants (105). Additional water within the stratum corneum could alter permeant solubUity and thereby modify partitioning from the vehicle into the membrane. Also, increased skin hydration may swell and open the structure of the stratum corneum, leading to an increased penetration. 

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Research on nasal powder drug delivery has employed polymers such as starch, dextrans, polyacrylic acid derivatives (e.g., carbopol, polycarbophil), cellulose derivatives (microcrystalline cellulose, semicrystalline cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose), chitosan, sodium alginate, hyaluronans, and polyanhydrides such as poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA). Many of these polymers have already been used as excipients in pharmaceutical formulations and are often referred to as first-generation bioadhesives [38-45], In nasal dry powder a single bioadhesive polymer or a... 

Intra-articular hyaluronan (lA-HA) injections are widely used to treat osteoarthritis (OA). This procedure is often referred to as viscosupplementation (22) because it involves the replacement of pathologic synovial fluid with viscoelastic hyaluro-nan-based solutions or gels. In the United States, lA-HA is specifically labeled as an intra-articular analgesic and is indicated to treat pain associated with knee OA when conservative measures and simple analgesics fail (e.g., acetaminophen). In other parts of the world, lA-HA is also approved for treatment of joints other than the knee and in some countries for arthritic conditions other than OA. The molecular basis for this application of hyaluronan, and the history of its development, has been recently reviewed (23). In this chapter, we will update the clinical evidence and describe the different types of hyaluronan formulations available in the United States. 

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