Isosorbide‐based polysebacates as polymeric components for development of in situ forming implants

Abstract

In situ forming implants (ISFIs) appear to be a convenient drug delivery system, alternative to conventional preformed implants and microparticles for parenteral drug delivery applications. It has been shown that they offer several advantages including easy and minimally invasive application, potential for local/site‐specific drug delivery that allows reduction of side effects associated with systemic administration of drug. A few ISFI formulations based on poly(α‐hydroxy acids), solidifying by solid phase separation, are currently commercially available. In this work, polyesters based on sebacic acid, isosorbide, and optionally 1,2‐propanediol were synthesized and characterized. Poly(isosorbide sebacate‐co‐1,2‐propylene sebacate) (PISEBPG) was chosen as an essential constituent of new ISFI formulations dedicated to controlled release of doxycycline hyclate (DOXY). Basic characteristics of new ISFI formulations were investigated. In particular, the influence of addition of a relatively hydrophobic cosolvent (triacetin, TA) to a more hydrophilic 1‐methyl‐2‐pyrrolidone (NMP) as well as the presence of calcium carbonate (CAC) on the morphology of resulted depots and DOXY release profile was evaluated. Scanning electron microscopy (SEM) analysis revealed that the presence of TA resulted in more porous morphology of the depots. DOXY has been releasing continuously from depots in vitro within 12 weeks depending on the composition. The release profile of the PISEBPG‐based formulation containing CAC indicates that it could be useful where short‐term (up to 14 d), rapid release of the antibiotic is required, while formulation without CAC, where after 21 days about 50% of the drug loaded may still be available for release, may be better for the long‐term delivery of DOXY.

Biodegradable Scaffolds for Vascular Regeneration Based on Electrospun Poly(L-Lactide-co-Glycolide)/Poly(Isosorbide Sebacate) Fibers

“…Although the applicability of PLGA in cardiovascular research is indisputable [ 11 , 12 ], PISEB is a material that has just started to be considered for its biomedical potential. In this study, PISEB was synthesized from isosorbide and diethyl sebacate in the presence of Novozyme ® 435 as a catalyst, by azeotropic method described earlier [ 19 , 36 ]. Both IS and sebacic acid (SBA) are derived from renewable resources (starch and castor oil, respectively), and were chosen for PISEB synthesis from a toxicological standpoint.…”

“…Poly(isosorbide sebacate) (PISEB) was synthesized as previously described [ 19 , 36 ]. Briefly, isosorbide (1.46 g, 0.01 mol) and diethyl sebacate (2.58 g, 0.01 mol) were heated in solvent mixture (cyclohexane:benzene = 6:1 v / v , 50 mL) together with Novozyme ® 435 (10 wt% of the monomers) used as polyesterification catalyst ( Scheme 1 ).…”

“…Unsaturated, IS-based resins have been proposed as polymerizable compounds of injectable biomaterials for bone surgery, either biodegradable or stable in physiological environments [ 16 , 17 ]. In turn, aliphatic IS-based polyesters have been investigated as a main component of parenteral antibiotic delivery systems such as in-situ-forming implants [ 18 , 19 ]. Recent literature studies report the use of IS-based polyesters in various biomedical fields, including fibroblast cell culture applications [ 20 ], wound dressing [ 21 ], and cardiovascular scaffolds [ 22 , 23 ].…”