Synthesis and characterization of functionalized biodegradable poly(DL‐lactide‐co‐RS‐β‐malic acid)

Abstract

Amorphous poly(DL-lactide-co-RS-beta-malic acid) (PDLLMAc) was synthesized by hydrogenolysis of poly(DL-lactide-co-RS-beta-malolactonate) (PDLLMA), which was obtained from the ring-opening polymerization of DL-lactide (DLLA) and RS-beta-benzyl malolactonate (MA) using stannous octoate as the catalyst. The amount of malolactonate (MA) in the feeding dose was varied from 0 to 8.0 mol %. The copolymers were characterized by 1H NMR, FTIR, GPC, and DSC. The tensile properties and water uptake of the copolymers were measured. The protective benzyl groups in PDLLMA were completely removed in hydrogenolysis to produce PDLLMAc. The molecular weight (M(n)) of the copolymers decreased with increasing MA content. However, with low feed MA content of 0.6 and 1.0%, high molecular weight PDLLMAc with M(n) of 63 and 35 kDa, respectively, were obtained; these copolymers exhibited good tensile yield stress and modulus of 17-23 MPa and 1.1-1.4 GPa, which are comparable to PDLLA homopolymer. The corresponding protected PDLLMA have tensile yield stress/modulus of 2.0-2.4 MPa and 11-42 MPa. The malic acid comonomer in PDLLMAc significantly improves the tensile strength and modulus compared to the protected PDLLMA. Further, the functionalizable PDLLMAc (with 0.6 mol % feed MA) was grafted with bioactive RGD peptide. The culture of primary umbilical artery smooth muscle cells was investigated. Methylthiazoletetrazolium results showed that both the RGD- and COOH-functionalized (0.6 mol %) PDLLMAc copolymers were significantly more biocompatible than the control PDLLA and could potentially be employed as tissue engineering scaffolds.

Blood compatibility evaluation of poly(d,l-lactide-co-beta-malic acid) modified with the GRGDS sequence

“…Polymers have expanded structures in good solvents, and form collapsed structures in poor solvents [16]. THF is a relatively good solvent for PDLLA, PLMA and P-GS5 [17]. Therefore, the same solvent THF was chosen for GPC measurements.…”

PHEA–PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions

“…The use of PLA-based copolymers instead of PLA alone for production of nanovectors could allow to obtain systems with tunable properties such as size, surface charge and hydrophilicity, and degradation rate (Saulnier et al, 2006), (He et al, 2008), (Li et 260 al., 2014), (Sheng et al, 2009), (Craparo et al, 2015).…”

Natural and synthetic poly(malic acid)-based derivates: a family of versatile biopolymers for the design of drug nanocarriers

“…The synthetic PMLA ( The 5FU has been covalently linked to the carboxylic acid lateral group through ester, amide or carbanoyl bounds using classical coupling reactions [59][60][61]. [58][59][60][61]103] Tissue engineering Physico-chemical characterization In vitro assays [70][71][72][73][74][75][76] Enteric coating materiels for tablets containing sodium diclofenac Physico-chemical characterizations [63][64][65] Micropattened tissue engineering scaffolds [66] Degradable hydrogel Physico-chemical characterizations Dox encapsulation In vitro assays [67,68] Coating matrix for smooth muscle cells [69] residues have been also chemically coupled on poly(α-malic acid)-5FU in order to evaluate the cell specific targeting of the resulting conjugate [60]. Ouchi et al have first studied the degradation of their macromolecular conjugates in vitro in order to determine the release of 5FU from poly(α-malic acid)-5FU conjugates [59][60][61].…”