Abstract
Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.
Highlights
IntroductionNanomaterials have been more and more widely used in biomedicine with the development of nanotechnology,[1,2,3] and nanomaterial-based drug sustainable release systems have been well developed.[4,5,6,7] The nanomaterial-based drug sustainable release systems have been widely used in tumor therapy and in tissue regeneration and in many other fields.[8,9,10] The sustainable release can enhance the drugs to retain their effects for a long time, avoid being rapidly metabolized, and ensure the efficacy of drugs.[11,12] At the same time, local drug release can increase drug concentration at the lesion site and decrease the side effects compared to other conventional deliveries.[13,14] Various drug sustainable release systems provide a novel means to effectively treat diseases.[15,16]An ideal nanomaterial-based drug sustainable release system should have higher capacity of drug load, and efficiently and slowly release drug to the target site.[17,18] External stimuli, such as laser, ultrasound, and magnetic field;[19] specific physical and chemical properties at target site, such as pH changes and glutathione content; and physiological environment of target site, can all affect drug release.[20,21] nanomaterials in drug sustainable release systems should have low toxicity and high biocompatibility, and it is better to be metabolizable and biodegradable in vivo.[22,23] Currently, only few nanomaterials can meet all requirements
Dopamine monomers can polymerize in this weakly alkaline mixture to form polydopamine on the surface of ZIF-8; with the further disintegration of ZIF-8, polydopamine NPs with hollow structure were obtained. This process was based on the chelation competition induced polymerization (CCIP) and HPDA NPs were synthesized with the breakdown of ZIF-8 and the polymerization of dopamine monomers
X-ray diffraction (XRD) analysis revealed that position and intensity of diffraction peaks of ZIF-8 correspond well to standard peaks, which was consistent with its crystal structure
Summary
Nanomaterials have been more and more widely used in biomedicine with the development of nanotechnology,[1,2,3] and nanomaterial-based drug sustainable release systems have been well developed.[4,5,6,7] The nanomaterial-based drug sustainable release systems have been widely used in tumor therapy and in tissue regeneration and in many other fields.[8,9,10] The sustainable release can enhance the drugs to retain their effects for a long time, avoid being rapidly metabolized, and ensure the efficacy of drugs.[11,12] At the same time, local drug release can increase drug concentration at the lesion site and decrease the side effects compared to other conventional deliveries.[13,14] Various drug sustainable release systems provide a novel means to effectively treat diseases.[15,16]An ideal nanomaterial-based drug sustainable release system should have higher capacity of drug load, and efficiently and slowly release drug to the target site.[17,18] External stimuli, such as laser, ultrasound, and magnetic field;[19] specific physical and chemical properties at target site, such as pH changes and glutathione content; and physiological environment of target site, can all affect drug release.[20,21] nanomaterials in drug sustainable release systems should have low toxicity and high biocompatibility, and it is better to be metabolizable and biodegradable in vivo.[22,23] Currently, only few nanomaterials can meet all requirements. Nanomaterials have been more and more widely used in biomedicine with the development of nanotechnology,[1,2,3] and nanomaterial-based drug sustainable release systems have been well developed.[4,5,6,7] The nanomaterial-based drug sustainable release systems have been widely used in tumor therapy and in tissue regeneration and in many other fields.[8,9,10] The sustainable release can enhance the drugs to retain their effects for a long time, avoid being rapidly metabolized, and ensure the efficacy of drugs.[11,12] At the same time, local drug release can increase drug concentration at the lesion site and decrease the side effects compared to other conventional deliveries.[13,14] Various drug sustainable release systems provide a novel means to effectively treat diseases.[15,16]. More rigorous design is needed to create an optimal drug sustainable release system
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