title: Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics.
abstract: Hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli. In this contribution, we outline a multifaceted hydrogel-based approach for expanding the range of therapeutics in oral formulations from classical small-molecule drugs to include proteins, chemotherapeutics, and nucleic acids. Through judicious material selection and careful design of copolymer composition and molecular architecture, we can engineer systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action. These hydrogel carriers, including complexation hydrogels, tethered hydrogels, interpenetrating networks, nanoscale hydrogels, and hydrogels with decorated structures are investigated for their ability to respond to changes in pH, to load and release insulin and fluorescein, and remain non-toxic to Caco-2 cells. Our results suggest these novel hydrogel networks have great potential for controlled delivery of proteins, chemotherapeutics, and nucleic acids.
authors.affiliation: Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Liechty
authors.forename: Mary
authors.initials: M
authors.lastname: Caldorera-Moore
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Phillips
authors.forename: Cody
authors.initials: C
authors.lastname: Schoener
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Peppas
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D001704:Biopolymers / Q000737:chemistry*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D004339:Drug Compounding; D006801:Humans; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D008027:Light; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009061:Mouth Mucosa / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy; D009696:Nucleic Acids / Q000008:administration & dosage*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011506:Proteins / Q000008:administration & dosage*; D012542:Scattering, Radiation; D012995:Solubility; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D001704:Biopolymers; D004337:Drug Carriers; D020100:Hydrogels; D009696:Nucleic Acids; D004364:Pharmaceutical Preparations; D011506:Proteins