The crucial role of macromolecular engineering, drug encapsulation and dilution on the thermoresponsiveness of UCST diblock copolymer nanoparticles used for hyperthermia.

Poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)), an upper critical solution temperature (UCST)-type copolymer in water, was synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization and used as a macro-RAFT agent for the polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) to yield amphiphilic diblock P(AAm-co-AN)-b-POEGMA copolymer. A series of copolymers with different AN content was obtained allowing to finely tune the UCST behavior (cloud point (Tt-UCST) from 35 to 78 °C). Addition of the POEGMA block did not modify the Tt-UCST regardless its Mn but provided a lower critical solution temperature behavior at high temperature. Nanoparticles were then formulated by the nanoprecipitation technique revealing that copolymers with higher Tt-UCST yield smaller, better-defined nanoparticles. Eventually, doxorubicin (Dox) was encapsulated into nanoparticles made from the copolymer having a Tt-UCST close to mild hyperthermia (~43 °C). Surprisingly, Dox encapsulation increased Tt-UCST and gave smaller nanoparticles as opposed to their unloaded counterparts. The dilution of the suspension also led to a decrease of Tt-UCST. No obvious hyperthermia effect was observed on the cytotoxicity of Dox-loaded nanoparticles. Our study highlighted the influence of macromolecular engineering, drug encapsulation and nanoparticle dilution on UCST behavior, important features often overlooked despite their crucial impact in the development of thermosensitive nanoscale drug delivery systems.

Restructuration kinetics of amphiphilic intraocular lenses during aging.

Photooxidation and hydrolysis are the two primary aging factors of intraocular lenses. Opacifications, dislocations, glistening and yellowing of the implanted acrylic lenses, which are due to chain scissions and depolymerization, are the consequences of aging from the clinical perspective. The purpose of this study was to examine the consequence of the aging of intraocular lenses on chemical and surface properties. Acrylic lenses made of poly acrylic-co-polystyrene polymer were artificially aged by photooxidation and hydrolysis from 2 to 20 years. Degradation products were observed by Reverse-phase High-Performance Liquid Chromatography RP-HPLC and thermogravimetric analysis (TGA). The surface, which was analyzed by atomic force microscopy (AFM) and fibronectin adhesion kinetics, was chosen as an indicator of intraocular biocompatibility. Low-molecular-weight degradation products (LMWP) result from chain scission under both hydrolysis and photooxidation. The osmotic effects of water enable degradation products to migrate through the polymer. A portion of the degradation products exudate in the surrounding center, whereas a portion link with lateral chains of the polymer. At the same time, the surface roughness evolves to externalize the most hydrophilic chains. As a result, the fibronectin adhesion level decrease with time, which indicates the existence of a biocompatible kinetic for implanted intraocular lenses.

Permeability of expander breast implants: In vitro and in vivo analyses.

INTRODUCTION: The biocompatibility of the polysiloxane breast implant has been studied moderately. The aging of these implants due to lipid penetration and the release of polymerization impurities, such as Platine or octamethylcyclotetrasiloxane (named D4), has already been documented. Since these studies, manufacturing procedures have been improved; thus, the security of breast implants has also improved. Although polymerization and the choice of monomer influence the shell properties, few studies have compared these together in breast implants. Our study compares the permeability and mechanical resistance of 3 breast expander shells after in vivo and in vitro aging. RESULTS: In vitro, all tested shells quickly sorbed linear molecules, such as fatty acids, and released siloxane impurities. The penetration of a molecule with steric hindrance, such as cholesterol, is slower. Allergan shells have the highest rates of molecule sorption and siloxane release. In vivo, after implantation, Allergan shells lost their initial mechanical properties over time. This observation was not found for mentor shells. For all brands, many biological molecules penetrate the shells, among which cholesterol and fatty acids are always present. DISCUSSION: The aging of polysiloxane shells depends on the sorption of many biological molecules and the release of siloxane impurities. The siloxanes are impurities and / or degradation products that are due to aging. Moreover, according to our results, the shells act as matrices that separate molecules according to their chemical and physical properties. CONCLUSION: Not all polysiloxane expander shells have the same properties during aging. The manufacturing procedures and the choice of siloxane monomers are the two most probative factors that explain the observed differences.

RP-HPLC detection and dosage method for acrylic monomers and degradation products released from implanted medical devices.

Acrylic copolymers are useful in medical therapeutics. As in dental implants or intraocular lenses, acrylics are present in many medical devices or drug adjuvants. Industrial using of acrylics is still important in painting or textile manufacturing. Scientific research background has proved that acrylic suffer for depolymerized and cross-linking mechanisms under heating and photo-oxidative conditions. Those aging processes could lead to release of unreacted monomers and degradation products. We developed a new RP-HPLC method with good resolution, recovery, linearity, detection and quantification limits that is efficient for acrylic monomers quantification in in vitro and in vivo saline solution matrices. This method allows the detection of copolymer and medical devices degradation products too. Both the limit of quantification and the limit of detection for monomers and degradation products are above cytotoxic concentrations for human epithelial cells. Those biological results confirm the interest of the method for dosage of unreacted acrylics after polymerization and for the research of degradation products in body fluids as aqueous humor.