Studies On The Hyaluronic Acid Coated Brucine Loaded Bovine Serum Albumin Nanoparticles

Osteoarthritis is a leading cause of chronic disability in the elderly.Due to its complex pathogenesis,there are currently no satisfactory treatments.The traditional treatment include symptomatic treatment with oral anti-inflammatory or intra-articular injected drugs for reducing pain and inflammation.Furthermore,there are major side effects in the treatments because of greatly increasing dosage of drugs.Therefore,how to improve the drug concentration in the articular cavity and to reduce the drug distribution in other tissues is the prevalence in researching the drug delivery of treating osteoarthritis.Intra-articular injected drugs could relieve gastrointestinal reactions caused by oral anti-inflammatory analgesic.Quick elimination of drug in the jiont cavity and frequent administration not only reduce the compliance of patient and also induce serious side effects.Albumin,a protein carrier for drug delivery,has been shown to be biocompatible biodegradable and non-immunogenic.Moreover,there is a number of reactive amino in the the surface,which provide the structural modification to drug carrier.It can be combined with the specific receptor to possess active targeting.Brucine,a pure alkaloid extracted from traditional Chinese medicine Srychnose pierriana A.W Hill.which can inhibit NO induced chondrocyte apoptosis,also effectively promote the proliferation of chondrocytes.Brucine have nervus centralis toxicity because of the stong liposolubility which greatly restrict the application.Therefore,how to improve their distribution in the joint cavity and reduce systemic side effects by means of pharmaceutics.Hyaluronic acid is a biocompatible anionic biopolymer and has a high affinity for the CD44 receptor expressed at the surface of chondrocytes.In the study,the aim is to specifically combine hyaluronic acid with CD44 receptor,which targetly transport drug to articular cavity and increase the drug concentration.Albumin nanoparticles as a drug carrier with sustained release,which can extend the retention time of drugs in the joint cavity.In the study,brucine bovine serum albumin nanoparticles were prepared by desolvation-chemical crosslinking method for intra-articular injection.The method of HPLC was set up to determine the concentration of brucine in the preparation and in vitro release.Applying particle size,encapsulation efficiency and drug-loading of nanoparticles to evaluate the quality of nanoparticles,the best formulation and process was screened by signal factor studies.The physical and chemical characters of nanoparticles were evaluated by TEM,FT-IR,DSC and X-ray.The mean diameter was 112.6±2.2nm,the Zeta potential was-32.64±0.85 mV,and the appearance was smooth and round without much adherence.The encapsulation efficiency was 49%,the drug loading was 8.2%.Animal in vivo imaging technology visually displayed the retention of NIR-15 labeled albumin nanoparticles and hyaluronic acid covered albumin nanoparticles in the joint cavity.The pharmacokinetics characters showed that brucine loaded albumin nanoparticles and hyaluronic acid coated albumin nanoparticles obviously delayed release compared with brucine solution.Accroding to the histological examinations of rats joint,there is no significantly pathological and physiological change between brucine loaded albumin nanoparticles,hyaluronic acid coated albumin nanoparticles and the saline group.That means the biocomapatibility of the preparation is good,and hence it might be suitable for long-term intra-articular injection.