Heparosan, a promising ‘naturally good’ polymeric conjugating vehicle for delivery of injectable therapeutics

Figures & data

Table 1. Characteristics of drug delivery systems.

Vehicle	Quasi-monodisperse?	Biodegradable?	Not immunogenic?
PEG	Yes	No	Sometimes
Heparosan	Yes	Yes	Yes
HES	No	Yes	Yes
PSA	No	Yes	Sometimes
Fusion	Yes	Yes	No*

The various vehicles have different production methods, purity and biological behavior in the body. The ideal delivery agent should have a ‘Yes’ response in all critical categories below.

* In theory, antibody production against any nonhuman polypeptide sequence is a possibility.

HES: Hydroxyethyl starch; PSA: Poly(sialic acid); Fusion: Fusion peptide composed of hydrophilic amino acids added by molecular genetic means to the cargo protein; quasi-monodisperse (i.e., very narrow size distributions approaching the ideal polydispersity value of 1).

Figure 1. Heparosan modification of drug cargo. Heparosan (curved lines), a polymer composed of [-4-N-acetylglucosamine-α1,4-glucuronic acid-β1-] repeats, is found in the heparan sulfate chains of mammals. This polymer in an unsulfated form can be attached to drug cargo (sphere) in a variety of formats to create conjugates with enhanced therapeutic action. Polysaccharide chains of different lengths, where n can range from 2 to ∼11,000, can be reacted at either a single site (left) or at multiple sites (right), as desired.