Synthesis and characterization of bioactive molecules grafted on poly(?-caprolactone) by “click” chemistry

A facile and efficient strategy to graft bioactive molecules (nicotinic acid, p-aminobenzoic acid, and phthaloyltryptophan) onto poly(?-caprolactone) (P(?CL)) was achieved by copper-catalyzed Huisgen’s 1,3-dipolar cycloaddition known as click reaction. P(αCl?CL), with 10, 20, and 30% of α-chloro-?-caprolactone (αCl?CL) units were copolymerized by ring opening polymerization using ?CL and αCl?CL as starting materials in the presence of 1,4-butanediol and Sn(Oct)₂. Subsequently, the chloride pendent was converted to azide followed by cycloaddition with terminal alkyne derivatives of the aforementioned bioactive molecules. The complete addition was accomplished at all ratios. The characteristic molecular features of these copolymers were evaluated by FTIR, NMR, and GPC. Thermal analysis data indicated that the grafted compounds led to polymorphic alteration and different pattern of thermal degradation depending on the molecular structure and the size of the grafted compounds. They are the basis for further development of grafted copolymer as drug delivery carriers.     

High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing

The self‐assembly of specific polymers into well‐defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high‐throughput method to screen the ability of polymers to self‐assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96‐well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high‐throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells.