Adhesive Drug Delivery Systems Based on Polyelectrolyte Complex Nanoparticles (PEC NP) for Bone Healing

Abstract

Drug loaded PEC NP consist of oppositely charged biorelated Polyelectrolytes (PEL) like ionic polysaccharides or ionic polypeptides and also synthetic PEL, which are mixed and processed in aqueous media. At first, freshly prepared drug/PEC NP exhibit time dependent colloidal stability in the range of weeks and months, which enables and simplifies storage, transport and application in the medical field. Secondly, after deposition and drying of drug/PEC NP a local wet adhesive PEC matrix at the BSM remains in contact to relevant aqueous media (e.g. buffer, cell culture medium), which minimizes asepsis, systemic toxicity, immune or inflammatory reaction. Thirdly, cell compatible PEC NP coatings were identified, which showed only minimal effects on various relevant bone related cells due to biorelateness, complexation, local confinement and low surface area. Fourthly, PEC NP elute drugs for bone healing like bisphosphonates, antibiotics and growth factors (e.g. bone morphogenetic proteins) in delayed and sustained manner. Moreover, the onset of elution could be triggered by thermoresponsive PEL via temperature increase giving clinicians a tool into hand allowing spatiotemporal drug release on demand. Finally, drug/PEC NP could be integrated into commercial or still developed allotropic stabilizing or defect filling BSM systems.

Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib

“…A promising approach to overcome the barriers in MM therapy is the functionalization of bone substitution materials (BSM) with coatings that deliver potent drugs directly to the anatomical site of action [8,9,10,11]. The two major advantages that derive from such local drug delivery systems are esteemed to be the reduction of the required total doses and more efficient attacking of hidden cancer cells in peripheral microlesions [9].…”

“…To create a suitable coating for this biomedical application, various conditions have to be fulfilled. Firstly the coating has to exhibit a strong adhesiveness towards the bone substitution material under wet conditions [8,11,12,13]. Otherwise, instability of the layer can occur and the detached layer material and drug could be transported to different parts of the body, causing damage.…”

“…Since the scale of requirements towards the applied coatings is very broad and can differ significantly with the respective drug, only highly alterable and adjustable systems qualify. Suitable systems are provided e.g., by polyelectrolyte complex nanoparticles (PEC NPs) [8,11,14,15]. In this approach, polyanions and polycations are complexed to nanoparticles in solution, which are subsequently immobilized to form the intended coatings.…”

Effects of BDNF and PEC Nanoparticles on Osteocytes

“…A possible way to avoid this is the loading of BDNF to a drug delivery system that releases the drug only at the place of interest but not systemically. Müller et al (2018) described that PECNP are a suitable system for loading of drugs and functionalization of bone substitute materials and implants [ 31 ]. Of course, the drug delivery system must be biocompatible.…”

Polyelectrolyte Gels: Fundamentals, Fabrication and Applications

“…Apart from polysaccharides, DDSs have also incorporated natural- or synthetic-based polymers such as PEI, poly( L -lysine), poly( L -glutamic acid) and PAA [ 179 , 187 , 188 ]. In an overview of different PEC combinations, it was demonstrated how the selection of the polymer and the construction of the system can affect several properties of the DDS [ 189 ]. Wet adhesion was only visible in ternary systems composed of the drug zoledronate (ZOL), PEI and CS, compared to binary systems composed of this drug and the two oppositely charged constituents.…”