Construction Of Curcumin-loaded Delivery System And Its Application In Anti-osteoporosis

Osteoporosis is a systemic bone disease characterized by loss of bone mass and destruction of the microscopic structure of bone,leading to bone pain and even fragility fractures.Currently,anti-osteoporosis drugs commonly used in clinic are mainly divided into two types,namely,anti-bone resorption drugs and bone-promoting drugs.The former includes estrogen,selective estrogen receptor agonists,bisphosphonates,calcitonin and RANKL polyclonal antibody,and the latter includes recombinant parathyroid hormone.Although there are many anti-osteoporosis drugs at present,the therapeutic effect is not ideal,long-term use will lead to some serious complications.Therefore,there is an urgent need to develop a new generation of safer drugs for anti-osteoporosis treatment.Polyphenols and flavonoids can be used as ideal anti-osteoporosis drugs because of their rich sources,low cost,low toxicity and dual anti-osteoporosis effects of inhibiting bone resorption and promoting bone formation.However,natural drug monomer itself is poor in water solubility,lack of targeting,and the effective concentration to play the curative effect is large.With the long-term use of drugs,the concentration of drugs in the body is increasing,which may have toxic and side effects on other tissues and organs,greatly limiting their clinical application.Nanomaterials are ideal drug carriers with the advantages of reducing drug toxicity,improving drug stability and slow and controlled release.However,due to the complex structure,harsh preparation conditions,low yield and other factors,it is difficult to realize large-scale production and conversion application of traditional nano drug delivery system.In addition,most of the vectors degrade slowly or even cannot be degraded in vivo,so excretion is blocked.Long-term use will accumulate in many important organs and tissues in the body,resulting in toxic side effects.To solve this problem,drug self-framing drug delivery system as a new drug transportation mode has attracted the attention of many scholars.This new drug delivery system does not require additional nanocarriers,but directly involves the active drug itself in the vector construction,which not only reduces the problems of high kidney burden brought by traditional drug carriers,complex and demanding preparation conditions and biocompatibility of the material itself,but also significantly increases the drug load,so it has attracted more and more attention.Based on this,we proposed to construct a self-framed nano-loaded drug system based on natural compounds.Through the careful design of the system,different types of self-framed nano drug delivery systems were obtained and given different functions.And to verify its anti-osteoporosis effect in vivo and in vitro.This paper is divided into the following two parts:(1)A new p H-responsive nano-drug delivery system(HCP NPs)was prepared by a simple ultrasonic polymerization method.Because of its amphiphilic properties,it can self-assemble into nanoparticles in aqueous solution and has excellent water dispersion.According to TEM and DLS,HCP NPs are approximately spherical and smooth nanoparticles with a particle size of about 120 nm.In addition,we demonstrated that HCP NPs has low biotoxicity and can be safely used in the medical field.The CLSM images showed that HCP NPs could enter the lysosome through endocytosis and release the Cur to play its biological function under the acidic environment in the lysosome.In vitro experiments have proved that HCP NPs can inhibit osteoclast differentiation and promote osteoblast differentiation,thus having the dual regulation ability of bone metabolism.In conclusion,this approach provides a new approach for designing an effective drug delivery system for osteoporosis.(2)Based on the previous chapter,bone targeting ligand ALN was introduced into the nano drug delivery system.The prepared HCPA NPs had good water solubility,nearly spherical morphology,average particle size of 181.9 ± 25.9 nm,and25.8wt% drug loading rate and p H response.In addition,based on the results of in vitro and in vivo experiments,we demonstrated that HCPA NPs has excellent bone targeting ability and can effectively prevent bone loss in OVX mice without significant toxicity to major organs.In summary,we have developed a simple and effective strategy to manufacture self-framing drug delivery systems with excellent physicochemical properties,high therapeutic efficacy,and low toxicity to provide a new approach for the treatment of osteoporosis.