Self-powered, light-controlled, bioresorbable platforms for programmed drug delivery.

Degradable polymer matrices and porous scaffolds provide powerful mechanisms for passive, sustained release of drugs relevant to the treatment of a broad range of diseases and conditions. Growing interest is in active control of pharmacokinetics tailored to the needs of the patient via programmable engineering platforms that include power sources, delivery mechanisms, communication hardware, and associated electronics, most typically in forms that require surgical extraction after a period of use. Here we report a light-controlled, self-powered technology that bypasses key disadvantages of these systems, in an overall design that is bioresorbable. Programmability relies on the use of an external light source to illuminate an implanted, wavelength-sensitive phototransistor to trigger a short circuit in an electrochemical cell structure that includes a metal gate valve as its anode. Consequent electrochemical corrosion eliminates the gate, thereby opening an underlying reservoir to release a dose of drugs by passive diffusion into surrounding tissue. A wavelength-division multiplexing strategy allows release to be programmed from any one or any arbitrary combination of a collection of reservoirs built into an integrated device. Studies of various bioresorbable electrode materials define the key considerations and guide optimized choices in designs. In vivo demonstrations of programmed release of lidocaine adjacent the sciatic nerves in rat models illustrate the functionality in the context of pain management, an essential aspect of patient care that could benefit from the results presented here.

Enhancing the Gene Transfection of Poly(ß-amino ester)/DNA Polyplexes by Modular Manipulation of Amphiphilicity.

Poly(ß-amino ester)s (PAEs) have been widely developed for gene delivery, and hydrophobic modification can further enhance their gene transfection efficiency. However, systematic manipulation of amphiphilicity of PAEs through copolymerization with hydrophobic monomers is time-consuming and, to some extent, uncontrollable. Here, a modular strategy is developed to manipulate the amphiphilicity of the PAE/DNA polyplexes. A hydrophobic polymer (DD-C12-122) and a hydrophilic polymer (DD-90-122) are synthesized separately and used as a hydrophobic module and a hydrophilic module, respectively. The amphiphilicity of polyplexes could be manipulated by changing the ratio of the hydrophobic module and hydrophilic module. Using the modular strategy, the PAE/DNA polyplexes with the highest gene transfection efficiency and safety profile as well as possible mechanisms are identified. The modular strategy provides a novel way to engineer the hydrophobicity of PAEs to improve their gene transfection and can be easily generalized and potentially extended to other polymeric gene delivery systems.

Phosphocholine-Functionalized Zwitterionic Highly Branched Poly(ß-amino ester)s for Cytoplasmic Protein Delivery.

Proteins have tremendous potential for vaccine development and disease treatment, but multiple extracellular and intracellular biological barriers must be overcome before they can exert specific biological functions in the target tissue. The use of polymers as carriers would greatly improve their bioavailability and therapeutic efficiency. Nevertheless, effective protein packaging and cell membrane penetration without causing cytotoxicity is particularly challenging, due largely to the simultaneous distribution of positive and negative charges on protein surface. Here, phosphocholine-functionalized zwitterionic poly(ß-amino ester)s, HPAE-D-(±), are developed for cytoplasmic protein delivery. The zwitterionic phosphocholine is capable of binding to both proteins and the cell membrane to facilitate protein packaging and nanoparticle cellular uptake. Compared to amine-functionalized HPAE-E-(+) and carboxylic acid-functionalized HPAE-C-(-), HPAE-D-(±) exhibits much higher cytoplasmic protein delivery efficiency and lower cytotoxicity. In addition, HPAE-D-(±) are readily degraded in aqueous solution. This strategy may be extended to other zwitterions and polymers, thus having profound implications for the development of safe and efficient protein delivery systems.