Biocompatibility of Poly(ester amide) (PEA) Microfibrils in Ocular Tissues

Abstract

Drug delivery systems (DDS) are able to deliver, over long periods of time, therapeutic concentrations of drugs requiring frequent administration. Two classes of DDS are available, biodegradable and non-biodegradable. The larger non-biodegradable implants ensure long-term delivery, but require surgical interventions. Biodegradable biomaterials are smaller, injectable implants, but degrade hydrolytically and release drugs in non-zero order kinetics, which is inefficient for long-term sustained drug release. Biodegradable poly(ester amides) (PEAs) may overcome these difficulties. To assess their ocular biocompatibility and long-term behavior, PEA fibrils were analyzed in vitro and in vivo. In vitro, incubation in vitreous humor changes to PEA structure, suggests degradation by surface erosion, enabling drug release with zero order kinetics. Clinical and histological analysis of PEA fibrils implanted subconjunctivally and intravitreally showed

Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

“…We hypothesized that intradiscal application of PEAs in the avascular IVD would be well accepted, in line with previous studies showing a moderate subcutaneous tissue response to a hydrogel that showed no response at all upon intradiscal injection. 32 Furthermore, safe intravitreal application of PEA fibrils through a 26G needle was already shown by Kropp et al 13 Indeed, PEAMs were considered safe within a 6 months follow-up period, based on clinical signs, disc height index, T2 values, biomolecular and biochemical analyses, and IVD histopathology. The focal, mild granulomatous reaction described in one of the PEAM injected IVDs could have been a consequence of leakage of the PEAMs, the injection procedure itself, or it could have been a reaction consistent with the ongoing process of IVD degeneration.…”

“…The median histopathological grade of noninjected (12; range: 10-15), sham-injected (14; range: 11-17), and PEAMs-injected IVDs 13 (11)(12)(13)(14)(15) was not significantly different. Representative histopathological images (picrosirius red/alcian blue stain) of all conditions are shown in Figure 1(B', B'', C', C'', and D', D'').…”

“…PEAs were synthesized according to a previously published method. 13,20 Briefly, the polymer was prepared via polycondensation of 0.45 equivalents of di-ptoluenesulfonic acid salts of bis-(L-leucine)1,4-dianhydrosorbitol diester (1), 0.30 equivalents of bis-(L-leucine) a,x-hexanediol diester (2), 0.25 equivalents of lysine benzyl ester (3), and 1 equivalent of di-N-hydroxysuccinimide ester of sebacic acid (4) in anhydrous dimethylformamide and trimethylamine in a glass vessel with overhead stirrer under a nitrogen atmosphere. Employing pre-activated acid in the reaction allows polymerization at a relative low temperature (658C), resulting in a polycondensate free of by-products and predictable degradation components.…”

“…PEAs can be manufactured by a polycondensation method and mechanical and thermal properties can be easily tuned . They have been successfully applied as a coating on coronary stents for sustained drug release, and were proven to meet the requirements of a biocompatible controlled release system in the ocular environment . To our knowledge, the intradiscal application of microspheres consisting of PEAs, has not been examined thus far, and seems a promising method to provide sustained release of bioactive substances over a prolonged period in the confined environment of the IVD.…”

Biodegradable Polymeric Films and Membranes Processing and Forming for Tissue Engineering

“…Transparency is an inherent property of material, Ozcelik et al demonstrated that chitosan–PEG hydrogel films that can achieve more than 95% of optical transparency . Although nowadays there is some biodegradable ocular product for drug delivery and treatment, such as OZURDEX (Allergan, USA) which is made from PLGA and has been used clinically, no commercial biodegradable polymer film/membrane is available in the market for ocular regeneration or reconstruction.…”