Analytical and Simulation-Based Models for Drug Release and Gel-Degradation in a Tetra-PEG Hydrogel Drug-Delivery System

• DOI: 10.1021/acs.macromol.5b01598
• Publication Date: 2015-09-30T11:15:02Z
• Authors: Ralph Reid; Miriam Sgobba; Barak Raveh; Giulio Rastelli; Andrej Sali; Daniel V. Santi
• Keywords: Degradation

We have recently reported drug-releasing, degradable Tetra-PEG hydrogels as a new drug delivery system. The gels contain two self-cleaving β-eliminative linkers: one that covalently tethers the to gel and releases it at predictable rate, another with slower cleavage is installed in each cross-link of polymer control degradation. By balancing rates, system can be designed discharge most or all before undergoes significant If degradation too rapid, undesirable gel-fragments bound are released; if slow, remains body an inert substance for prolonged periods. Here, we describe analytical theory well Monte Carlo simulation concurrent release from polymers. Considerations made ideal network networks containing missing bonds double link defects. approaches perfect agreement other experimental data regime interest. Using these models, able (a) compute time courses amount fragment–drug conjugate present any (b) estimate rate constants necessary above. also account size-dependent elimination fragments localized semipermeable compartment hence fragment mass vs curves such vivo compartments. models described allow design optimal vehicle particular use.