Polyketal Copolymers: A New Acid-Sensitive Delivery Vehicle for Treating Acute Inflammatory Diseases

Yang, Stephen C.; Bhide, Mahesh; Crispe, Ian Nicholas; Pierce, Robert H.; Murthy, Niren

doi:10.1021/bc700442g

Cited by 109 publications

(123 citation statements)

References 19 publications

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“…Because the production of ROS and activity of antioxidants demonstrated chamber-specific characteristics, local delivery of an H 2 O 2 scavenger (ebselen) using polyketal nanoparticles (PK3) was performed [50]. In preliminary studies, there was no effect of free ebselen injected directly into the tissue (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Age- and Chamber-Specific Differences in Oxidative Stress After Ischemic Injury

et al. 2011

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Each year, tens of thousands of children undergo cardiopulmonary bypass (CPB) to correct congenital heart defects. Although necessary for surgery, CPB involves stopping the heart and exposing it to ischemic conditions. On reoxygenation, the heart can experience effects similar to that of acute myocardial infarction. Although much is known about adult injury, little is known about the effects of global ischemia on newborn ventricles. We studied newborn (2 to 4 days old) and adult (>8 weeks old) rabbit hearts subjected to ischemia–reperfusion (30 min of ischemia and 60 min of reperfusion). Our data demonstrated chamber- and age-specific changes in oxidative stress. During ischemia, hydrogen peroxide (H2O2) increased in both right-ventricular (RV) and left-ventricular (LV) myocytes of the newborn, although only the RV change was significant. In contrast, there was no significant increase in H2O2 in either RV or LV myocytes of adults. There was a fivefold increase in H2O2 formation in newborn RV myocytes compared with adults (P = 0.006). In whole-heart tissue, superoxide dismutase activity increased from sham versus ischemia in the left ventricle of both adult and newborn hearts, but it was increased only in the right ventricle of the newborn heart. Catalase activity was significantly increased after ischemia in both adult ventricles, whereas no increase was seen in newborn compared with sham hearts. In addition, catalase levels in newborns were significantly lower, indicating less scavenging potential. Nanoparticle-encapsulated ebselen, given as an intracardiac injection into the right or left ventricle of newborn hearts, significantly increased functional recovery of developed pressure only in the right ventricle, indicating the potential for localized antioxidant therapy during and after pediatric surgical procedures.

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Section: Resultsmentioning

confidence: 99%

Age- and Chamber-Specific Differences in Oxidative Stress After Ischemic Injury

et al. 2011

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“…FTIR measurements were performed on a Digilab Stingray system consisting of a FTIR 7000e stepscan spectrometer (Varian Inc.). 13 C NMR spectra were obtained using a Varian Gemini 200 MHz NMR spectrometers. A Shimadzu Prominence LC-20 AB HPLC system installed with a Waters 2410 refractive index detector was used to calculate molecular weight using GPC.…”

Section: Methodsmentioning

confidence: 99%

Antioxidant Activity of Degradable Polymer Poly(trolox ester) to Suppress Oxidative Stress Injury in the Cells

Wattamwar

Wan

et al. 2009

Adv Funct Materials

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Oxidative stress is a pathological condition that has been implicated as a central player in a variety of diseases, including vascular and neurodegenerative diseases. More recently, oxidative stress has also been shown to be involved in the biological incompatibility of many materials, especially at the nanoscale. As such, there is a critical need for new biomaterials that can inhibit this response, improving the compatibility of medical devices. In this work, trolox, a synthetic antioxidant and water‐soluble analogue of Vitamin E, is polymerized to form an oxidation active polymer as a new class of biomaterial. Synthesized poly(trolox ester) polymers were formulated into nanoparticles using a single emulsion technique, and their size was controlled by changing the polymer concentration in the organic solvent. Nanoparticle cytotoxicity, protective effects against cellular oxidative stress, and degradation kinetics were all evaluated. Poly(trolox ester) nanoparticles were found to have little to no cytotoxicity and were capable of suppressing cellular oxidative stress induced by cobalt nanoparticles. In vitro degradation studies of poly(trolox ester) nanoparticles indicate that the antioxidant activity of nanoparticles was derived from its enzymatic degradation to release active antioxidants.

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“…A polyoxalate based polymer system has been shown to be biodegradable, biocompatible, and provide better cell viability as compared to PLGA [77]. Polyketal copolymers have been shown to deliver imatinib effectively, but the inflammatory response warrants further investigation [78]. …”

Section: Evaluation Of Key Plga Concepts To Identify Issues In Depmentioning

confidence: 99%

Injectable controlled release depots for large molecules

Schwendeman

Shah

Bailey

et al. 2014

Journal of Controlled Release

171

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Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.

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Polyketal Copolymers: A New Acid-Sensitive Delivery Vehicle for Treating Acute Inflammatory Diseases

Cited by 109 publications

References 19 publications

Age- and Chamber-Specific Differences in Oxidative Stress After Ischemic Injury

Age- and Chamber-Specific Differences in Oxidative Stress After Ischemic Injury

Antioxidant Activity of Degradable Polymer Poly(trolox ester) to Suppress Oxidative Stress Injury in the Cells

Injectable controlled release depots for large molecules

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