Semisynthetic Hydrophilic Polyals

Abstract

Nonbioadhesive, fully biodegradable soluble polymers would be very instrumental in advanced biomedical applications, such as gene and drug delivery and tissue engineering. However, rational development of such materials is hindered by the complexity of macromolecule interactions with biological milieu. The prevalence of carbohydrates in naturally occurring interface structures suggests an alternative, biomimetic approach. Interface carbohydrates, regardless of their biological function, have common nonsignaling substructures (e.g., acetal and ketal groups, secondary and primary alcohols). We hypothesized that hydrophilic polymers (polyals) consisting of acyclic units built of nonsignaling carbohydrate substructures would be highly biocompatible and nonbioadhesive, while intrachain acetal or ketal groups would enable nonenzymatic biodegradation upon uptake by cells. Acyclic hydrophilic polyals can be prepared via either polymerization of suitable monomers or lateral cleavage of cyclic polyals (e.g., polysaccharides). In this study, model polyals were produced via lateral cleavage of polyaldoses and polyketoses. Best results were achieved using dextran B-512 as a precursor. The resultant poly[hydroxymethylethylene hydroxymethylformal], in agreement with the hypothesis, demonstrated excellent biological properties and technological flexibility. Materials of this type can potentially have several applications in pharmacology and bioengineering.

Responsive Polymers at the Biology/Materials Science Interface

“…The chemistries employed have included polyacetals, ketals, and hydrazones. [41][42][43] In comparison to the 'one-shot' approaches described above, reversibly responsive polymers are especially applicable in devices or materials to combat conditions such as diabetes, where a specific or feedback-controlled release profile might be required. Polymers that respond in such a way to changes in local glucose concentrations by releasing insulin have been much studied [44][45][46][47] following initial reports by Ishihara and co-workers.…”

Fully Degradable Hydrophilic Polyals for Protein Modification

“…All previously tested PHF-containing preparations with MW exceeding 70 kDa exhibited long circulation in vivo, with no significant uptake in RES. The blood half-life of unmodified 500 kDa PHF was found to be over 24 h. 10,28 At a 1:1 polymer/protein ratio, two conjugation techniques gave the highest coupling yields (95-98% by protein): the one-step method utilizing aminooxy-NHS coupling reagent VIII and polymer succinylation followed by EDC-mediated acylation. Conjugate formation was accompanied with a 1.5 to 2.0-fold increase in the number-average molecular weight (M n ).…”

“…The structures of all obtained polymers, as examined by 13 C and 1 H NMR, were consistent with the expected acyclic polyacetal structure. 10,28 PHF-glycol PHF-glycol was prepared by controlled dextran cleavage that was stopped at stage II, with subsequent reduction of intermediates (IIa, IIb). The starting glucopyranoside/periodate molar ratio was 1:1.90.…”

Recent Developments in Cyclic Acetal Biomaterials for Tissue Engineering Applications

“…While polyesters and polyanhydrides are all widely characterized and under development for biomedical applications, they are not biologically inert and may non-specifically react with the surrounding in vivo environment (53). Polyesters and polyanhydrides, as well as other similarly structured polymers, degrade via hydrolysis and give rise to products with carboxylic acid terminal groups.…”

“…Previous studies have also shown that accumulation and increased concentration of acidic degradation products can induce tissue toxicity (28,29,56). To address these issues, a new class of synthetic, polymeric biomaterials based upon degradable units such as acetals, cyclic acetals, and ketals have been developed (22,24,53).…”