title: Feedback regulated drug delivery vehicles: carbon dioxide responsive cationic hydrogels for antidote release.
abstract: A possible approach to handling the harmful side effects of an analgesic overdose, without losing its therapeutic potential, involves feedback regulated delivery of an antidote. For example, overdose of morphine causes hypoventilation, an inadequate ventilation to perform gas exchanges in lungs leading to increased CO2 concentration in the blood. Taking advantage of CO2 as a toxicity marker, a hydrogel-based delivery vehicle containing dimethylamino groups [poly(N,N-dimethylaminoethyl methacrylate) cross-linked by trimethylolpropane trimethacrylate] was designed. Stimulus controlled swelling of these hydrogels in naloxone delivery is discussed. A remarkable control over naloxone release was achieved against the concentration of the biomarker. The overall stimuli response of the gel could be enhanced further by encapsulating carbonic anhydrase, a metalloenzyme known to catalyze the reversible hydration of CO2. Thus, a feedback regulated drug delivery vehicle based on toxicity biomarker strategy was modeled successfully, which has the potential to mitigate risks associated with drug overdose.
authors.affiliation: Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Sunita S
authors.initials: SS
authors.lastname: Satav
authors.forename: Shreedhar
authors.initials: S
authors.lastname: Bhat
authors.forename: S
authors.initials: S
authors.lastname: Thayumanavan
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000633:toxicity; D000931:Antidotes / Q000008:administration & dosage*; D015415:Biomarkers; D002245:Carbon Dioxide / Q000097:blood*; D002412:Cations; D016503:Drug Delivery Systems / Q000379:methods*; D062787:Drug Overdose / Q000188:drug therapy / Q000517:prevention & control*; D025461:Feedback, Physiological; D020100:Hydrogels / Q000627:therapeutic use*; D007040:Hypoventilation / Q000139:chemically induced; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage
chemical_list: D000700:Analgesics; D000931:Antidotes; D015415:Biomarkers; D002412:Cations; D020100:Hydrogels; D009292:Narcotic Antagonists; D002245:Carbon Dioxide; D009270:Naloxone; D009020:Morphine