Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB

Abstract

The development of a vascular network in tissue-engineered constructs is a fundamental bottleneck of bioregenerative medicine, particularly when the size of the implant exceeds a certain limit given by diffusion lengths and/or if the host tissue shows a very active metabolism. One of the approaches to achieve the vascularization of tissue constructs is generating a sustained release of proangiogenic factors from the ischemic site. This work describes the formation and characterization of hyaluronic acid-chitosan (HA/CS) nanoparticles for the delivery of two pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF-BB). These nanoparticles were prepared by an ionic gelification technique, and different formulations were developed by encapsulating the growth factors in association with two stabilizing agents: bovine serum albumin or heparin sodium salt. These carriers were characterized with regard to their physicochemical properties, their stability in biological media, and their cytotoxicity in the C3a hepatoma cell line. The results show that nanoparticles around 200 nm can be prepared by this method. HA/CS nanoparticles were stable when incubated in EMEM cell culture medium or in water at 37°C for 24 h. Cell culture tests confirmed that HA/CS nanoparticles are not cytotoxic within the concentration range used for growth factor delivery. Moreover, HA/CS nanoparticles were able to entrap efficiently both growth factors, reaching association values of 94% and 54% for VEGF and PDGF, respectively. In vitro release studies confirm that PDGF-BB is released from HA/CS nanoparticles in a sustained manner over approximately 1 week. On the other hand, VEGF is completely released within the first 24 h.

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

“…The reason behind the significantly (p = 0.003) smaller size of CNAC nanoparticles compared to the chitosan particles was the stronger intermolecular interactions resulting from CNAC's thiol group (53,54) . The incorporation of HA with chit/TPP did not influence the particle size significantly (chit/TPP-HA; 350.7 ± 2.5 nm) compared to chit/TPP (345.5 ± 2.5 nm; p = 0.11) but was larger than previously-reported HA chitosan nanoparticles (163 -182 nm) (55,56) . Native Ranibizumab had a size of 8.37 ± 0.2 nm which is in line with a previous study (57) .…”

The effective combination therapy against human osteosarcoma: doxorubicin plus curcumin co-encapsulated lipid-coated polymeric nanoparticulate drug delivery system

“…Stability study in the serum was determined in the presence of serum (Parajó et al, 2010). Samples were incubated in phosphate buffers (PBS) solution containing 10% (v/v) FBS at 37…”

Chemical functionalization of bone implants with nanoparticle-stabilized chitosan and methotrexate for inhibiting both osteoclastoma formation and bacterial infection

“…DA was as the first layer because it was proved that it could not only well coat the pristine Ti substrates but also electrostatically bind to heparin 10, 28, 29 . CH was introduced along with MTX to form the last layer on Ti because as a biocompatible polymer rich in amine groups, it can bind to various drugs 30, 31 or growth factors 32, 33 , regulate their release, and also inhibit bacterial adhesion. The immobilization of CH/MTX on PLL/Hep-Ti substrates can be easily achieved via the electrostatic interactions between the amine groups of CH/MTX and the carboxylic/sulfate groups of heparin.…”