18 research outputs found
Nanoparticle system for the local delivery of disease modifying osteoarthritic drugs
Purpose: The purpose of this study is to develop the nanoparticles that i) can be injected intra-articularly ii) target to cartilage due to an opposite charge difference with the extracellular cartilaginous matrix and iii) due to their small size can penetrate into the cartilage. In this way retention time in the joint can be prolonged. By releasing disease modifying OA drugs (DMOAD) in the vicinity of chondrocytes such materials may be beneficial for restoring cartilage tissue homeostasis. Here we demonstrate the generation of drug-containing nanoparticles for intra-articular joint therapy. Methods: We have prepared nanoparticles of biodegradable poly ethylene glycol- poly lactic acid PEG-PLA co-block polymers. The hydrophilic PEG and hydrophobic PLA ends of this polymer make it possible to generate micelles that contain drugs. The polymers are functionalized with UV-sensitive acrylate groups that can be stabilized by UV-crosslinking. These drug containing nanoparticles will be used for intra-articular joint injection and release of DMOADs. We have also established co-culture systems in vitro using MSCs and chondrocytes where the effect of these molecules and nanocarriers can be tested. Results: Micelle type nanoparticles using PEG-PLA co-block polymers were prepared. The obtained dexamethasone loaded nanoparticles had diameters of 20-80 nm. These nanoparticles are photo-crosslinked at their hydrophobic cores which provides stability to the structure and resulted in a slight decrease in average particle size . Dexamethasone was successfully encapsulated in these nanoparticles. The current release profiles show initial burst release in the first 8 hours followed by a sustained release over at least 3 days. Conclusions: We have generated nanoparticles that can serve as a carrier system to deliver clinically relevant disease modifying osteoarthritic drugs in a more effective way after intra-articular injection. We are currently investigating the retention of nanoparticles in the joint and are developing strategies to target these particles to cartilag
Macrophage selective photodynamic therapy by meta-tetra(hydroxyphenyl)chlorin loaded polymeric micelles: A possible treatment for cardiovascular diseases
Biodegradable hydrogels by physical and enzymatic crosslinking of biomacromolecules
Cartilage can be damaged due to trauma or diseases like osteoarthritis. These damages cause pain and impair normal articulation of the joint. Current strategies like microfracture, mosaicplasty and autologous chondrocyte implantation for cartilage repair relieve pain and improve joint function but it has been shown that these procedures only lead to a temporary solution. The newly formed tissue often lacks the properties of native cartilage and shows signs of deterioration after 1 year. An alternative approach to cartilage repair is tissue engineering. Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences towards the reconstruction or development of biological substitutes that restore, maintain or improve tissue functions 1. In tissue engineering generally scaffolds are used to provide a stable temporary matrix for cells in order to grow new tissue. Since a hydrogel is a material that closely resembles the natural environment of cells in cartilage, research in tissue engineering of cartilage has mainly focused on these materials to act as a temporary matrix. Although many materials have been designed and prepared to form hydrogels several issues still have to be tackled. One of these issues is the adhesion of hydrogels to the surrounding tissue at the implant site. Hereto we have performed a fundamental study of the effects of incorporating positively charged moieties in amphiphilic block copolymers on their aggregation and (thermo-reversible) gelation behavior and on the formation of physically crosslinked hydrogels. The rationale is to increase the adhesion properties of physically crosslinked hydrogels to soft tissues like cartilage that have an ECM that is negatively charged. Furthermore, we have studied the influence of the chemical structure and aggregation behavior of tyramine substituted synthetic and natural polymers on their enzymatic crosslinking, an ongoing research subject in our group. Research was aimed at developing injectable and biodegradable scaffolds with controlled degradation times, which support chondrocyte survival and matrix production
Nanoparticle system for the local delivery of disease modifying osteoarthritic drugs
Purpose: The purpose of this study is to develop the nanoparticles that i) can be injected intra-articularly ii) target to cartilage due to an opposite charge difference with the extracellular cartilaginous matrix and iii) due to their small size can penetrate into the cartilage. In this way retention time in the joint can be prolonged. By releasing disease modifying OA drugs (DMOAD) in the vicinity of chondrocytes such materials may be beneficial for restoring cartilage tissue homeostasis. Here we demonstrate the generation of drug-containing nanoparticles for intra-articular joint therapy.
Methods: We have prepared nanoparticles of biodegradable poly ethylene glycol- poly lactic acid PEG-PLA co-block polymers. The hydrophilic PEG and hydrophobic PLA ends of this polymer make it possible to generate micelles that contain drugs. The polymers are functionalized with UV-sensitive acrylate groups that can be stabilized by UV-crosslinking. These drug containing nanoparticles will be used for intra-articular joint injection and release of DMOADs. We have also established co-culture systems in vitro using MSCs and chondrocytes where the effect of these molecules and nanocarriers can be tested.
Results: Micelle type nanoparticles using PEG-PLA co-block polymers were prepared. The obtained dexamethasone loaded nanoparticles had diameters of 20-80 nm. These nanoparticles are photo-crosslinked at their hydrophobic cores which provides stability to the structure and resulted in a slight decrease in average particle size . Dexamethasone was successfully encapsulated in these nanoparticles. The current release profiles show initial burst release in the first 8 hours followed by a sustained release over at least 3 days.
Conclusions: We have generated nanoparticles that can serve as a carrier system to deliver clinically relevant disease modifying osteoarthritic drugs in a more effective way after intra-articular injection. We are currently investigating the retention of nanoparticles in the joint and are developing strategies to target these particles to cartilag
Enzymatically crosslinked polysaccharide based hydrogels as an extracellular matrix for cartilage tissue engineering
Evaluation of tubular poly(trimethylene carbonate) tissue engineering scaffolds in a circulating pulsatile flow system
Introducing small cationic groups into 4-armed PLLAePEG copolymers leads to preferred micellization over thermo-reversible gelation
Starting from bis-MPA, PEGePLLA triblock copolymers (bis-MPA-(PLLAePEG)2), comprising a central Nhydroxysuccinimide active ester, were synthesized. Reacting the corresponding active ester with a,udiamines afforded four-armed (PEGePLLA)2eRe(PLLAePEG)2 copolymers with central a,u-diamide groups (R). Applying the a,u-diamines, hexamethylene-diamine, spermine or norspermidine none, one or two secondary amine groups, respectively, were introduced into the linking moiety R. Whereas a copolymer containing no secondary amine groups showed fully thermo-reversible gelation behavior, copolymers comprising a central moiety containing one or two secondary amine groups retained the ‘sol’ state after a few heating and cooling cycles. Dynamic light scattering revealed that the copolymer containing no secondary amine groups showed a thermo-reversible shift in micellar size and small aggregates (57 and 877 nm at 25 C and 40 and 152 nm at 50 C). Conversely, copolymers comprising a central moiety containing secondary amine groups show a temperature independent distribution mainly consisting of micelles. It is proposed that the protonated amine groups preferably are located at the corona of the micelles and micellar aggregates and/or shielded by the PEG blocks, hindering the formation of hydrogels by PEG entanglements upon a change in temperature