Hyaluronan: Pharmaceutical Characterization and Drug Delivery

Figures & data

FIG. 1 The primary, secondary, and tertiary structures of HA in solutions. (A) The primary structure of HA consists of repeating dissacharide units of D-glucoronic acid and N-acetyl-D-glucosamine with up to 5 hydrogen bonds existing between each two neighboring disaccharides. The secondary structures are formed as tape-like 2-fold helices by twisting each disacchride unit through 180° compared with those ahead and behind it in the chain. (B) The β -sheet tertiary structure tertiary structure is energetically stabilized by interactions between hydrophobic patches hatched and intermolecular hydrogen bonding between the acetamido ▪and □ and carboxylate groups (• and ○). (C) Schematic networks of HA molecules as a results of intermolecular aggregation (Reprinted with permission from Scott and Heatley 1999).

TABLE 1 Summary of the medical applications of HA

Disease state	Applications	Commercial products	Publications
Osteoarthritis	Lubrication and mechanical support for the joints	Hyalgan®(Fidia, Italy), Artz® (Seikagaku, Japan) Orthovisc® (Anika, USA) Healon®, Opegan®, and Opelead®	Hochburg 2000; Altman 2000; Dougados 2000; Guidolin et al. 2001; Maheu et al. 2002; Barrett et al. 2002; Miltner et al. 2002; Tascioglu 2003; Uthman et al. 2003; Kelly et al. 2003; Hamburger et al. 2003; Kirwan 2001; Ghosh et al. 2002; Mabuchi et al. 1999; Balazs 1998; Fraser et al. 1993; Zhu et al. 2003.
Surgery and wound healing	Implantation of artificial intraocular lens Viscoelastic gel	Bionect®, Connettivina® and Jossalind®	Ghosh 2002; Risberg 1997; Inoue et al. 1993; Miyazaki et al. 1996; Stiebel-Kalish et al. 1998; Tani et al. 2002; Vazquez et al. 2003; Soldati et al. 1999; Ortonne 1996; Cantor et al. 1998, Turino et al. 2003.
Embryo implantation	Culture media for the use of in vitro fertilization	EmbryoGlue® (Vitrolife, USA)	Simon et al. 2003; Gardner et al. 1999; Vanos et al. 1991; Kemmann 1998; Suchanek 1994; Joly et al. 1992; Gardner 2003; Lane 2003; Figueiredo 2002; Miyano 1994 Kano et al. 1998; Abeydeera 2002; Jaakma et al. 1997, Furnus et al. 1998; Jang 2003.

FIG. 2 The effect of 1% w/w polysaccharide on the percentage of applied diclofenac (1.75% w/w) delivered to the skin, 48 hr after application of the formulation (n = 4, mean ± standard deviation, *p < .001 compared with control).

TABLE 2 Summary of the drug delivery applications of HA

Route	Justification	Therapeutic agents	Publications
Ophthalmic	Increased ocular residence of drug that can lead to increased bioavailability	Pilocarpine, tropicamide, timolol, gentimycin, tobramycin, arecaidine polyester, (S) aceclidine	Jarvinen et al. 1995; Sasaki et al. 1996; Gurny et al. 1987; Camber et al. 1987, 1989; Saettone et al. 1994, 1991; Bucolo et al. 1998, 1999; Herrero-Vanrell et al. 2000; Moreira et al. 1991a, 1991b; Bernatchez et al. 1993, Gandolfi et al. 1992; Langer et al. 1997
Nasal	Bioadhesion resulting in increased bioavailability	Xylometazoline, vasopressin, gentamycin	Morimoto et al. 1991; Lim et al. 2002.
Pulmonary	Absorption enhancer and dissolution rate modification	Insulin	Morimoto et al. 2001; Surendrakumar et al. 2003.
Parenteral	Drug carrier and facilitator of liposomal entrapment	Taxol, superoxide desmutase, human recombinant insulin-like growth factor, doxorubicin	Drobnik 1991; Sakurai et al. 1997; Luo et al. 1999, 2000; Prisell et al. 1992, Yerushalmi et al. 1994, 1998; Peer et al. 2000; Eliaz et al. 2001; Peer et al. 2003.
Implant	Dissolution rate modification	Insulin	Surini et al. 2003; Takayama et al. 1990
Gene	Dissolution rate modification and protection	Plasmid DNA/monclonal antibodies	Yun et al. 2004; Kim et al. 2003.

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