Specific Thermoresponsive Behaviours Exhibited by Optically Active and Inactive Phenylalanine Modified Hyperbranched Polyethylenimines in Water

Optically active and inactive hyperbranched polymers with specific thermoresponsive behaviours in water were reported.Through two steps hyperbranched polyethylenimine（HPEI） polymers terminated with different amount of D-phenylalanine（D-Phe）,L-phenylalanine（L-Phe） or DL-phenylalanine（DL-Phe） were prepared and characterized.The analyses on the solution properties by turbidimetry,dynamic light scattering,fluorescence probe and 1H-NMR demonstrated that all the polymers exhibited specific thermoresponsive behaviours in water,including：（1） In the dilute polymer concentration region,increasing the polymer concentration led to the increase of phase transition temperature;（2） The optically inactive thermoresponsive hyperbranched polymers showed a higher cloud-point temperature（Tcp） than their corresponding optically active ones in a relatively higher polymer concentration;（3） At the same polymer concentration the hydrophobic groups of the optically inactive HPEI-DL-Phe formed more perfect hydrophobic domain than those of the optically active HPEI-L-Phe and HPEI-D-Phe.

Crystalline inclusion complexes formed between the drug diflunisal and block copolymers

The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.