title: Potential avoidance of adverse analgesic effects using a biologically "smart" hydrogel capable of controlled bupivacaine release.
abstract: Acute pain remains a tremendous clinical and economic burden, as its prevalence and common narcotic-based treatments are associated with poorer outcomes and higher costs. Multimodal analgesia portends great therapeutic promise, but rarely allows opioid sparing, and new alternatives are necessary. Microparticles (MPs) composed of biodegradable polymers [e.g., poly(lactic-co-glycolic acid) or PLGA] have been applied for controlled drug release and acute pain treatment research. However, foreign particles' presence within inflamed tissue may affect the drug release or targeting, and/or cause a secondary inflammatory reaction. We examined how small alterations in the particulate nature of MPs affect both their uptake into and subsequent activation of macrophages. MPs composed of PLGA and chitosan (PLGA-Chi) loaded with bupivacaine (BP) were engineered at different sizes and their opsonization by J774 macrophages was assessed. Uptake of PLGA-Chi by macrophages was found to be size dependent, but they were not cytotoxic or proinflammatory in effect. Moreover, encapsulation of MPs in a thermoresponsive loading gel (pluronic F-127) effectively prevented opsonization. Finally, MPs displayed sustained, tunable release of BP up to 7 days. These results demonstrate our ability to develop a drug delivery system capable of controlled release of local anesthetics to treat acute/subacute pain while concurrently avoiding enhanced inflammation.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030; Pain Therapy Service, University of Pavia-Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030; Bioceramics and Bio-Hybrid Materials, National Research Council of Italy - ISTEC, Faenza, Ravenna 48018, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Minardi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030; Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona 60131, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Corradetti
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030; Department of Biomedical Engineering, University of Houston, Houston, Texas.
authors.forename: Iman K
authors.initials: IK
authors.lastname: Yazdi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030.
authors.forename: Marta A
authors.initials: MA
authors.lastname: Balliano
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030; Department of Surgery, Houston Methodist Hospital, Houston, Texas 77030.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Van Eps
authors.affiliation: Pain Therapy Service, University of Pavia-Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinic Surgical Pediatric and Diagnostic Sciences, University of Pavia, Pavia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Allegri
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030. Electronic address: etasciotti@houstonmethodist.org.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry* / Q000633:toxicity; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry* / Q000633:toxicity; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010316:Particle Size; D010587:Phagocytosis; D020442:Poloxamer / Q000737:chemistry* / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D018836:Inflammation Mediators; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D002045:Bupivacaine
keywords: biomaterials; controlled release; drug delivery; inflammation; injectables; microparticles; pain