注射式复合纳米人工骨的生物相容性和降解性能的实验研究

目的:观察新型可注射式纳米羟基磷灰石(n-HA)/半水硫酸钙(CSH)人工骨体外细胞毒性和家兔体内埋植后组织反应以及降解性能,并探讨其可能的生物降解机制.方法:对纯CSH、纯n-HA、10%n-HA CSH、20%n-HA CSH和40%n-HA CSH复合材料共5种材料进行体外MTT细胞毒性试验.将20%n-HA CSH人工骨植入家兔肌肉和右侧股骨钻孔缺损内,分别在术后5 d及2、3、4、5、6、8、12周观察埋植后家兔的一般情况、复合材料的改变情况、肌肉组织病理和透射电镜表现以及骨组织病理和影像学变化.结果:培养细胞在5种材料浸提液中各自的平均细胞增殖率均在77%以上,细胞毒性均为0～1级.20%n-HA CSH复合材料在动物体内埋植后无全身反应,体质量均稳步增加.埋植区肌肉组织大体观察发现,术后5 d至8周复合材料从表面-主体-核心以分层方式降解,术后8周时复合材料基本降解,肌肉未出现纤维化、钙化或异位骨化.H-E染色可见降解过程初期散乱的人工骨材料为大量炎性细胞浸润、包绕,逐渐被分解为碎片,成纤维细胞逐渐转化为纤维细胞并包绕吞噬前期分解的材料碎片.电镜显示该降解由组织细胞吞噬反应介导,而且吞噬细胞并未出现胞膜损害和细胞器异常.右侧股骨骨组织影像学和病理学检查发现术后6周见缺损处松质骨内明显新生骨形成,8～12周人工骨完全降解,缺损处已具有正常骨小梁形态.结论:20%n-HA CSH复合材料人工骨无明显体外细胞毒性,生物相容性良好;动物体内降解可能是由组织细胞吞噬反应介导以分层方式降解,骨内8～12周完全降解,速度符合骨再生需要,具备很好的成骨活性.     

携载两性霉素B的聚氰基丙烯酸正丁酯纳米粒的制备及特性评价

目的:制备携载两性霉素B(AmB)的聚氰基丙烯酸正丁酯(PBCA)纳米粒,测定表征,并筛选制备工艺.方法:将抗真菌药物AmB以孵化法吸附在PBCA空白纳米粒上,制备两性霉素B-聚氰基丙烯酸正丁酯纳米粒(AmB-PBCA-NP),并以聚山梨酯-80进行表面修饰.检测所制备AmB-PBCA-NP溶液的D405值,利用AmB的标准方程计算AmB药物浓度并评价药物溶液的稳定性;Nano-S粒径测定仪测定粒径分布;将AmB-PBCA-NP胶体溶液离心后,取上清液测定浓度,按公式计算纳米粒的包封率及载药量等指标;进行体外释放实验;以不同处方条件下纳米粒的粒径、载药量和包封率为评价指标筛选优化的处方工艺.结果:制备的AmB-PBCA-NP外观呈圆或类圆形,平均粒径(69.01±28.56) nm,分散均匀;AmB标准品在1.12～5.60 μg/ml范围内的线性回归方程为:D405=0.163 4c 0.006 6,r=0.999 3,AmB-PBCA-NP的平均回收率为99.93%,其溶液在12 h内稳定性较好;体外释放实验表明24 h体外释放具有一定的缓释性;实验发现最优化的处方为稳定剂采用DextranT-70,且不加助溶剂脱氧胆酸钠,其包封率及载药量均比较高,分别为56.10%、82%.结论:该方法工艺简单易行,载药纳米粒性状符合药剂学要求.     

Utilizing RNA nanotechnology to construct negatively charged and ultrasound-responsive nanodroplets for targeted delivery of siRNA

Ultrasound nanodroplets (NDs) have been reported as a promising nanocarrier for siRNA delivery depending on its unique strengths of sonoporation. Presently, common means for NDs-mediated siRNA delivery is through electrostatic interaction, but challenges like cationic toxicity still exist. In this study, we demonstrated a novel strategy to construct negatively charged and ultrasound (US)-responsive O-carboxymethyl chitosan (O-CMS) NDs as a siRNA targeted delivery system through three-way junction of bacteriophage phi29 DNA packaging motor (3WJ-pRNA) nanotechnology. 39nt A10-3.2 aptamer targeting prostate specific membrane antigen (PSMA) and 21nt siRNA against cationic amino acid transporter 1 (siCAT-1) were annealed to 3WJ-pRNA scaffold via complementation with an extended sequence. The cholesterol molecule attached to one branch facilitates the 3WJ-pRNA nanoparticles anchoring onto NDs. The desired O-CMS NDs with siRNA-loading and RNA-aptamer modification (A10-3.2/siCAT-1/3WJ-NDs) were successfully prepared, which were with spherical shapes, core–shell structures and uniform in sizes (198 nm with PDI 0.3). As a main proportion of shell, O-CMC showed a certain anti-tumor effects. In vitro studies demonstrated that A10-3.2/siCAT-1/3WJ-NDs exhibited good contrast-enhanced US imaging, buffering capacity and high bio-safety, were able to deliver siCAT-1 to PSMA-overexpressed prostate cancer cells under US irradiation, thus silence the CAT-1 expression, and consequently suppressing 22RV1 cell proliferation and migration. Taken overall, our findings provide a promising strategy to develop negatively charged and US-responsive NDs for tumor-targeted siRNA delivery.     

Synthesis and Potential Applications of Lipid Nanoparticles in Medicine

Currently, carriers of active ingredients in the form of particles of a size measured in nanometers are the focus of interest of research centers worldwide. So far, submicrometer emulsions, liposomes, as well as microspheres, and nanospheres made of biodegradable polymers have been used in medicine. Recent studies show particular interest in nanoparticles based on lipids, and at the present time, are even referred to as the “era of lipid carriers”. With the passage of time, lipid nanoparticles of the so-called first and second generation, SLN (Solid Lipid Nanoparticles) and nanostructured lipid carriers and NLC (Nanostructured Lipid Carriers), respectively, turned out to be an alternative for all imperfections of earlier carriers. These carriers are characterized by a number of beneficial functional properties, including, among others, structure based on lipids well tolerated by the human body, high stability, and ability to carry hydro- and lipophilic compounds. Additionally, these carriers can enhance the distribution of the drug in the target organ and alter the pharmacokinetic properties of the drug carriers to enhance the medical effect and minimize adverse side effects. This work is focused on the current review of the state-of-the-art related to the synthesis and applications of popular nanoparticles in medicine, with a focus on their use, e.g., in COVID-19 vaccines.     

Nanotechnology: A Focus on Nanoparticles as a Drug Delivery System

This review will provide an in-depth discussion on the previous development of nanoparticle-based drug delivery systems (DDS) and discuss original research data that includes the therapeutic enhancement of antiretroviral therapy. The use of nanoparticle DDS will allow practitioners to use drugs to target specific areas of the body. In the treatment of malignancies, the use of nanoparticles as a DDS is making measurable treatment impact. Medical imaging will also utilize DDS to illuminate tumors, the brain, or other cellular functions in the body. The utility of nanoparticle DDS to improve human health is potentially enormous.     

In vitro exposure of bull sperm cells to DMSA-coated maghemite nanoparticles does not affect cell functionality or structure

Magnetic nanoparticles can be used in different areas of biology. It is therefore important to know the effects of such nanomaterials on germline cells as they may traverse the blood-testis barrier. This work aimed to evaluate the response of bull sperm after exposure to a magnetic fluid containing DMSA-coated maghemite nanoparticles (MNP-DMSA) in order to determine nanotoxicity. Bull sperm was incubated with MNP-DMSA at final concentrations of 0.06, 0.03 or 0.015?mg Fe/mL. Sperm kinetics, plasma membrane integrity and acrosome reaction were evaluated over a 4?h incubation period. The sperm cells were also evaluated by transmission electron microscopy. Exposure of bull sperm to MNP-DMSA did not affect sperm kinetics or integrity. Neither ultrastructural damage of sperm cells nor uptake of nanoparticles by the spermatozoa was observed. In conclusion, MNP-DMSA does not affect sperm function or structure under the conditions tested.     

The therapeutic potential of targeting ABC transporters to combat multi-drug resistance

Introduction: Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect.

Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters. We integrated our current knowledge at different levels from molecular biology to clinical trials. We also discussed potential therapeutic strategies of targeting ABC transporters to reverse MDR in cancer cells.

Expert opinion: Involvement of various ABC transporters to cancer MDR lays the foundation for developing tailored therapies that can overcome MDR. An ideal MDR reversal agent should have broad-spectrum ABC-transporter inhibitory activity, be potent, have good pharmacokinetics, have no trans-stimulation effects, and have low or no toxicity. Alternatively, nanotechnology-based drug delivery systems containing both the cytotoxic drug and reversing agent may represent a useful approach to reversing MDR with minimal off-target toxicity.     

Spotlight on the delivery of photosensitizers: different approaches for photodynamic-based therapies

Introduction: Nanomedicine development allowed the discovery of new photosensitizers (PS) and drug delivery systems (DDS) to overcome current issues on phototherapy. Nano-engineered materials have the potential to improve the solubility of PS, control drug pharmacokinetics, decreasing side effects, increasing bioavailability, and overcoming multidrug resistance. A recent approach is the co-delivery of PS with other therapeutic agents in a multimodal platform for synergic and improved results.

Areas covered: This paper discusses the delivery of PS-nanostructured platforms for conventional, photothermal, and antimicrobial photodynamic therapies, as well as in a recent therapeutic modality for photobiomodulation, covering applications of cancer diagnosis, targeting to skin pathogens, photoregeneration and wound healing. The focus of the present review is to describe the use of different DDS to enhance the therapeutic outcomes triggered by the combination of delivered PS, light, and oxygen.

Expert opinion: Nanotechnology allowed the development of site-specific delivery of PS molecules, expanding possibilities poorly explored before to enhance photodynamic efficacy and extrapolate the concept to other treatment protocols. Research in this area embraces potential and pitfalls of PS delivery, allowing new clinical phase outcomes and long-term issues to be established, which will impact on several biomedical applications.