Functionalized poly(lactic-co-glycolic acid) enhances drug delivery and provides chemical moieties for surface engineering while preserving biocompatibility

Abstract

Poly(lactic-co-glycolic acid) (PLGA) is one of the more widely used polymers for biomedical applications. Nonetheless, PLGA lacks chemical moieties that facilitate cellular interactions and surface chemistries. Furthermore, incorporation of hydrophilic molecules is often problematic. The integration of polymer functionalities would afford the opportunity to alter device characteristics, thereby enabling control over drug interactions, conjugations, and cellular phenomena. In an effort to introduce amine functionalities and improve polymer versatility, we synthesized two block copolymers (PLGA-PLL 502H and PLGA-PLL 503H) comprised of PLGA and Poly(ε-carbobenzoxy-L-lysine) utilizing dicyclohexyl carbodiimide (DCC) coupling. PLGA-PLL micropsheres encapsulated approximately six-fold (502H) and three-fold (503H) more vascular endothelial growth factor (VEGF), and 41% (503H) more ciliary neurotrophic factor (CNTF) than their PLGA counterparts. While the amine functionalities were amenable to the delivery of large molecules and surface conjugations, they did not comprise polymer biocompatibility. With the versatile combination of properties, biocompatibility, and ease of synthesis, these block copolymers have the potential for diverse utility in the fields of drug delivery and tissue engineering.

Intravenously administered nanoparticles increase survival following blast trauma

“…All reagents were ACS grade and were purchased from Thermo Fisher Scientific. PLGA-PLL-PEG block copolymer was created using standard bioconjugation techniques as described previously (26).…”

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system

“…15 PLGA and PLL-CBZ were dissolved in anhydrous DMF under a nitrogen atmosphere, and the dried products PLGA-PLL-CBZ were dissolved in a sufficient amount of 33% hydrogen bromide, and stirred for 2 hours; the off-white polymer was dried under vacuum for 12 hours to produce the deprotected PLGA-PLL. 16 PEG was dissolved in dioxane, to which CDI was added at room temperature, to synthesize the activated PEG. The solution remaining in the dialysis tube was freeze-dried for 3 days to produce activated PEG-CDI.…”

Using Polymer Chemistry to Modulate the Delivery of Neurotrophic Factors from Degradable Microspheres: Delivery of BDNF

“…1 shows the reaction scheme for the synthesis of PLGA-PLL-PEG. PLGA-PLL was coupled as described previously (18,19). Ultraviolet-visible (UV-Vis) spectroscopy and 1 H-NMR characterization confirmed successful conjugation with an average conjugation efficiency of approximately 30%.…”

“…1) (18,19). Briefly, PLGA 503H and poly(ε-carbobenzoxy-L-lysine) (1:1 molar ratio) were dissolved in dimethyl formamide (DMF).…”

“…The successful conjugation of poly(ε-carbobenzoxy-Llysine) and PLGA was determined as previously described (18,19). The successful conjugation of PEG to PLGA-PLL was determined using 1 H NMR.…”