title: From micro- to nanostructured implantable device for local anesthetic delivery.
abstract: Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release.
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering 'G. Natta', Politecnico di Milano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zorzetto
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering 'G. Natta', Politecnico di Milano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brambilla
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering 'G. Natta', Politecnico di Milano, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Marcello
authors.affiliation: Department of Molecular Medicine, Centre for Health Technologies (CHT), INSTM UdR of Pavia, University of Pavia, Pavia, Italy.
authors.forename: Nora
authors.initials: N
authors.lastname: Bloise
authors.affiliation: Pain Therapy Service, IRCCS Foundation Policlinico San Matteo Pavia, Pavia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: De Gregori
authors.affiliation: General Surgery Department, IRCCS Foundation Policlinico San Matteo, Pavia, Italy; Departments of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cobianchi
authors.affiliation: General Surgery Department, IRCCS Foundation Policlinico San Matteo, Pavia, Italy; Departments of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Peloso
authors.affiliation: Department of Surgical Sciences, University of Parma, Parma, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Allegri
authors.affiliation: Department of Molecular Medicine, Centre for Health Technologies (CHT), INSTM UdR of Pavia, University of Pavia, Pavia, Italy; Department of Occupational Medicine, Toxicology and Environmental Risks, S. Maugeri Foundation, IRCCS, Lab of Nanotechnology, Pavia, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Visai
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering 'G. Natta', Politecnico di Milano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Petrini
mesh_terms: D020341:Absorbable Implants; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D020100:Hydrogels; D008081:Liposomes; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry*; D011091:Polyesters
chemical_list: D000779:Anesthetics, Local; D001672:Biocompatible Materials; D020100:Hydrogels; D008081:Liposomes; D011091:Polyesters
keywords: liposomes; microencapsulation; microparticle; nanogels; nanoparticle production; pain management