Study on the stability and H+ permeable membrane properties of polymersomes / 药学实践杂志

Objective To prepare polymersomes (PSs) by block copolymers，evaluate their membrane structural stability，investigate the H+ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H+ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H+ concentration and t1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H+ transmembrane coefficients for the three types of PSs were reduced by 2.39×104, 3.38×104, and 5.48×108 times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.

Research progress of platelets and their derivatives based drug delivery systems / 中国输血杂志

Platelets play an important role in physiological and pathological activities such as thrombosis, inflammation and tumorigenesis. At present, the application of platelets in drug delivery systems is increasingly studied. Compared with traditional drug delivery systems, new drug delivery systems based on platelets and their derivatives can effectively improve the circulation time and selective accumulation, and reduce the occurrence of related immune reactions or off-target toxic and side effects. In this paper, the types and applications of platelet and its derivatives drug delivery systems were summarized in order to provide reference for platelet-related drug delivery research.

Mitochondrial-targeted and ROS-responsive nanocarrier via nose-to-brain pathway for ischemic stroke treatment

Oxidative stress injury and mitochondrial dysfunction are major obstacles to neurological functional recovery after ischemic stroke. The development of new approaches to simultaneously diminish oxidative stress and resist mitochondrial dysfunction is urgently needed. Inspired by the overproduced reactive oxygen species (ROS) at ischemic neuron mitochondria, multifunctional nanoparticles with ROS-responsiveness and mitochondrial-targeted (SPNPs) were engineered, achieving specific targeting delivery and controllable drug release at ischemic penumbra. Due to the nose-to-brain pathway, SPNPs which were encapsulated in a thermo-sensitive gel by intranasal administration were directly delivered to the ischemic penumbra bypassing the blood‒brain barrier (BBB) and enhancing delivery efficiency. The potential of SPNPs for ischemic stroke treatment was systematically evaluated in vitro and in rat models of middle cerebral artery occlusion (MCAO). Results demonstrated the mitochondrial-targeted and protective effects of SPNPs on H2O2-induced oxidative damage in SH-SY5Y cells. In vivo distribution analyzed by fluorescence imaging proved the rapid and enhanced active targeting of SPNPs to the ischemic area in MCAO rats. SPNPs by intranasal administration exhibited superior therapeutic efficacy by alleviating oxidative stress, diminishing inflammation, repairing mitochondrial function, and decreasing apoptosis. This strategy provided a multifunctional delivery system for the effective treatment of ischemic injury, which also implies a potential application prospect for other central nervous diseases.

Current research trends of nanomedicines

Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment, nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects. Nanomedicines hold tremendous theranostic potential for treating, monitoring, diagnosing, and controlling various diseases and are attracting an unfathomable amount of input of research resources. Against the backdrop of an exponentially growing number of publications, it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines. Herein, this review elaborates on the development trends of nanomedicines, emerging nanocarriers, in vivo fate and safety of nanomedicines, and their extensive applications. Moreover, the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed. The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.

Progress in preparation and application of biomimetic nano carriers for cell membrane / 药学实践杂志

Nanocarriers prepared from organic or inorganic materials are widely used in drug targeting system and diagnosis and treatment of disease. However, there are some problems, such as poor targeting, short circulation time in vivo and improvement in the biocompatibility. Biomimetic nanocarriers has carried out research on the issues, which based on different kinds of cell membrane for the nanocarriers modification, endogenous biofilm improving the biocompatibility of carriers in vivo, more accurate targeting, and even producing immunotherapeutic effect. The principle, method, targeting mechanism and therapeutic effect of biomimetic nano carrier technology of cell membrane have been reviewed in this paper, which provide a new direction for the research of new drug delivery system.

Oral and nasal vaccination: current prospects, challenges, and impact of nanotechnology-based delivery systems

Abstract Currently, mucosal vaccine administration has stood out as an easier and non-invasive application method. It can also be used to induce local and systemic immune responses. In the COVID-19 pandemic context, nasal and oral vaccines have been developed based on different technological platforms. This review addressed relevant aspects of mucosal vaccine administration, with emphasis on oral and nasal vaccinations, in addition to the importance of using nanotechnology-based delivery systems to enable these strategies.

Research progress of smart responsive nanocarriers for nucleic acid drug delivery / 中国药房

Nucleic acid drugs ha ve received increasing attention and are considered to be potential for the therapy of many diseases such as tumor therapy. This is due to their selective regulation of specific protein expression ，simple sequence design ，easy synthesis and modification ，and clear mechanism of action. However ，nucleic acid drugs have to be delivered by carriers to produce therapeutic effects ，because nucleotides must rely on effective carriers to overcome their limitations and various transmembrane barriers. Currently ，most non-viral nucleic acid delivery carriers have the disadvantage of poor transfection efficiency. The researchers design a series of smart responsive nanocarriers that respond to the pathological environments in vivo or physical stimulations in vitro . By responding to internal special changes such as pH values and redox conditions or to external stimuli such as temperature ，ultrasound，magnetic field and light ，the smart responsive nanocarriers can achieve precise regulation of drug release ，enhance the transfection efficiency of nucleotides in target cells and reduce the toxic side effects on normal tissues and cells. This review summarizes the progress of smart responsive nanocarriers in the field of nucleic acid drugs delivery and introduces the functional design and features of smart responsive nanocarriers. The intent is to provide a reference for the development of nucleic acid drugs and their delivery systems.

Development and in vivo evaluation of lipid-based nanocarriers containing Jatropha isabellei dry extract from the dichloromethane fraction intended for oral treatment of arthritic diseases

In this study, a dichloromethane fraction dry extract from the underground parts of Jatropha isabellei (DFJi) was used to prepare lipid nanocarriers (LNCJi) aimed at providing the oral delivery of terpenic compounds in the treatment of arthritis. The lipid nanocarriers were prepared by the spontaneous emulsification method. The lipid nanocarriers displayed sizes ranging from 180 to 200 nm and zeta potential values of around -18 mV. A high value of entrapment efficiency (> 90%) was obtained for jatrophone, which was used as the chemical marker of DFJi. LNCJi stored at 4°C were demonstrated to be stable through measurements of transmitted light after analytical centrifugation of the samples. In vitro drug release studies conducted in biorelevant dissolution media demonstrated that jatrophone release was faster from LNCJi than from free DFJi. When tested in an acute arthritis model, the LNCJi exhibited antinociceptive properties after oral administration of a 50 mg/kg dose, unlike the free DFJi, although no reduction in articular diameter was observed. These results suggest that an increase in the oral absorption of DFJi constituents may have occurred through the carrying of this fraction in LNCJi, thus improving the antinociceptive activity of this compound

Antitumor strategies based on targeted modulation of tumor-associated macrophages / 中国药科大学学报

@#Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in tumors, which generally exhibit anti-inflammatory M2 phenotypes, and are the key inducers of tumor development, metastasis and drug resistance, and thus becoming a popular target in the field of antitumor immunotherapy.The study and application of nanocarriers optimize TAMs-targeted antitumor therapy.According to the characteristics and functions of TAMs, modulation strategies based on TAMs are elaborated, including TAMs depletion, inhibition of TAMs recruitment and TAMs repolarization.At the same time, in order to apply the above strategies more efficiently and overcome the general off-target problems in treatment, specific TAMs-targeted therapies based on nanocarriers are reviewed and analyzed, including passive targeting to TAMs, active targeting to macrophages and specifically active targeting to M2-TAMs. Finally, based on the limitations of targeting TAMs alone, new therapeutic strategies of targeting both TAMs and tumor cells via nanocarrier based delivery systems are introduced to provide new ideas for the application of these strategies in the field of tumor immunotherapy and combination therapy with other antitumor strategies.

The reversed intra- and extracellular pH in tumors as a unified strategy to chemotherapeutic delivery using targeted nanocarriers

Solid tumors are complex entities, comprising a wide variety of malignancies with very different molecular alterations. Despite this, they share a set of characteristics known as "hallmarks of cancer" that can be used as common therapeutic targets. Thus, every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates, and these adaptations lead to alterations in extra- and intracellular pH. These changes in pH are common to all solid tumors, and can be used either as therapeutic targets, blocking the cell proton transporters and reversing the pH changes, or as means to specifically deliver anticancer drugs. In this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic adaptations. We will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light exposure. Finally, we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery, describing how nanocarriers are being used to increase drug stability and specificity.

Synergistic chemo-photothermal therapy of castration-resistant prostate cancer by single-walled carbon nanotube / 上海交通大学学报（医学版）

Objective : To study the synergistic effect of chemo-photothermal on castration-resistant prostate cancer (CRPC) for enhancing the efficacy of chemotherapy by single-walled carbon nanotubes (SWCNTs). Methods ¡¤ High-purity SWCNTs were used as the drug carrier. Firstly, SWCHTs were truncated (shorten SWCNTs, s-SWCNTs) by mixed acid solutions. At the same time, a large amount of -COOH were in-troduced onto the surface of s-SWCNTs. Secondly, the polyethylene glycol (PEG) with amino terminated was successfully modified onto s-SWCNTs through amido linkage in N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride solutions to endow s-SWCNTs with water solubility and biocompatibility. Finally, docetaxel (DTX) was successfully loaded through nano-deposition method and π-π stacking on the surface of s-SWCNTs. Thus a nanosystem with both chemotherapy and photothermal properties was established. The chemo-photothermal therapy synergistic inhibition on CRPC cell line C4-2 in vitro and the anti-tumor effect in vivo were evaluated. Results ¡¤ Fourier transform infrared spectrum and zeta potential test showed that -COOH was successfully introduced onto s-SWCNTs, and the amount of -COOH was 0.412 mol per gram of SWCNTs determined by automatic conduct metric titration. The UV absorption spectrum showed that DTX was successfully loaded onto the nanosystem. By monitoring the UV absorption of the dialysate, DTX could be loaded onto SWCNTs up to 1.35 mg per gram of s-SWCNTs. Under the stimulation of acidic conditions, DTX could be rapidly released from the surface of the nanosystem. The in vitro cell viability and in vivo anti-tumor experiment showed that DTX combined with photothermal had a synergetic effect on killing C4-2 cells than any single treatment model. Conclusion ¡¤ DTX-loaded s-SWCNTs nanosystem with high stability and photothermal effect can inhib-it the growth of CRPC cells and the tumor growth in mice bearing CRPC. The nanosystem with synergistic effect of chemotherapy and photo-thermal therapy could be used in the treatment of prostate cancer which is resistant to chemotherapy drugs.

Research Progress of Nano-drug Delivery Systems for Active Ingredients from Chinese Materia Medica by Modulating EMT to Inhibit Tumor Metastasis / 中国实验方剂学杂志

The epithelial-to-mesenchymal transition (EMT), a process during which cells undergo transition from a polarized epithelial phenotype to a non-polarized mesenchymal phenotype, executed by transcription factors of Twist, Snail and Zeb families. EMT plays an important role in multiple stages of cancer progression such as initiation, tumor growth, and metastasis. Some active ingredients from Chinese materia medica can inhibit EMT by regulating transcription factors and signaling pathways by multiple targets. However, their therapeutic effect was hindered due to various limitation such as solubility, stability, tissue specificity and safety. Therefore, in order to improve the druggability of active ingredients from Chinese materia medica, enhance the therapeutic effect in inhibiting tumor metastasis mediated by EMT and reduce the toxic and side effects, a variety of nano-drug delivery systems have been developed in recent years. Here, we made a review about these drug delivery systems modulating EMT and their research progress in inhibiting tumor metastasis.

Research Progress on Organic-inorganic Hybrid Nanocarriers of Active Ingredients from Chinese Materia Medica / 中国实验方剂学杂志

Nanocarriers for delivering active ingredients from Chinese materia medica play an important role in improving their solubility, membrane permeability and in vivo biological behavior, enhancing the therapeutic efficiency and reducing side effects. They are promising for extensive research and application. As novel nanocarriers, organic-inorganic hybrid nanocarriers composed of organic materials or carriers and inorganic parts possess the dual advantages of organic carriers and inorganic carriers. They may exert desirable action in drug delivery. In addition, they have been designed to improve the stability and biocompatibility, further increase the therapeutic efficiency and reduce side effects. They have also been investigated to achieve multi-functionality. In this paper, the research and application of organic-inorganic hybrid nanocarriers delivering active ingredients from Chinese materia medica were summarized and analyzed. The development and application prospect of organic-inorganic hybrid nanocarriers are prospected. The aim of this review is to provide a reference for the investigation of new drug delivery system for delivering active ingredients from Chinese materia medica efficiently and safely.

Anti-melanoma effect of intratumoral injection of PD-L1-siRNA-loaded phenylboronic acid-modified chitooligosaccharide nanoparticles: a preliminary study / 国际药学研究杂志

Objective: To prepare phenylboronic acid-modified chitooligosaccharide(PBA-COS)nanoparticles(PBA-COS/ siPD-L1) loaded with PD-L1-siRNA(siPD-L1) and investigate the properties and in vivo anti -melanoma(B16F10) effect of the nanoparticles in mice. Methods: PBA-COS/siPD-L1 nanoparticles were prepared by the complex coacervation method. The particle size and Zeta potential of nanoparticles were investigated by dynamic light scattering. Agarose gel electrophoresis was used to evaluate the binding capacity of PBA-COS carriers to siRNA. The morphology of nanoparticles was observed by transmission electron microscope. In vitro cell uptake efficiency was analyzed by flow cytometry. The mouse subcutaneous B16F10 melanoma model was used to in- vestigate the in vivo effect of intratumoral injection of the nanoparticles on the tumor growth and metastasis. The apoptosis of tumor cells and the lung metastasis of tumors were analyzed and examined by TUNEL staining and HE staining, respectively. Results: The particle size of the PBA-COS/siPD-L1 nanoparticles was(101.9±1.89)nm and the Zeta potential was(25.6±1.52)mV. The nanoparticles were observed to be spherical under the transmission electron microscope. The nanoparticles were efficiently ingestible by B16F10 cells, and the intratumoral injection of the nanoparticles could inhibit tumor growth and lung metastasis of B16F10 melanoma in vivo in mice by inducing the B16F10 cell apoptosis. Conclusion: The intratumoral injection of PBA-OS/siPD-L1 nanoparticles could significantly inhibit tumor growth(the tumor inhibition rate was 42.4%, P<0.01)and lung metastasis of melanoma in mice.

Advances in the research of protein nanocarrier materials / 中国药科大学学报

@#Nanotechnology has brought new strategies in the area of pharmaceutical sciences, especially in the drug delivery system. Among them, the application of protein as drug carriers has drawn extensive attention. A wide variety of proteins that have been used fordrug delivery system including the common animal- and plant-basedproteins, as well as the recombinant protein nanoparticles, which possess many advantages such as biocompatibility, biodegradability, low antigenicity, higher stability and drug loading property. This system is of great significance in the fields of clinical treatment, especially targeted therapy of tumors. In this paper, the fabrication of nanoparticles from animal, botanical, and recombinant proteins are described. And then, trend of development in protein-based nanocarriers is also prospected.

Nanometer preparation of traditional Chinese medicine for rheumatoid arthritis / 中国中药杂志

Rheumatoid arthritis( RA) is a chronic autoimmune disease,which can occur at any age. Repeated severe attacks can cause joint deformities. Its pathogenesis is complex,and the pathophysiological process involves many different types of cells. At present,the pathogenesis of RA is still unclear,and the clinical medication mainly aims to alleviate inflammation and symptoms.DMARDs,non-steroidal anti-inflammatory drugs,adrenocortical hormones,biological agents and traditional Chinese medicine are all applied in clinic. Traditional Chinese medicine has a long history in the treatment of RA. In particular,traditional Chinese medicine compounds can treat RA through multiple target points. The combination of nanotechnology and anti-inflammatory traditional Chinese and western medicines has also attracted extensive attention. Nanotechnology can selectively deliver drugs to articular cavity by taking advantage of its small carrier size and biodegradable materials. It can reduce the size of drug delivered,and increase the accuracy,safety and effectiveness of drugs,and further improve the therapeutic efficacy of drugs on RA. In this paper,traditional Chinese and western medicines and their nano-preparations used in the treatment of RA were reviewed in the past five years. The researches of nano-preparation were discussed in terms of pharmacology category. This paper provided reference for the research and development of new-type nano-preparation with outstanding clinical efficacy.

Research Progress on Strategies of Overcoming Doxorubicin Resistance Based on Nanocarriers / 中国药学杂志

Multidrug resistance (MDR) refers to the cross-resistance of tumor cells to multiple chemotherapeutic drugs, which stems from long-term exposure to a certain chemotherapeutic drug. MDR is the most important defense mechanism for tumor cells and the main reason to failure of tumor chemotherapy. As a promising drug delivery system, nanocarriers can effectively overcome MDR by enhancing drug targeting to tumors, releasing drug selectively, increasing cellular uptake, the introduction of photochemical, and deliveing multiple active molecules synergistically. In this review, the progress on applications of nanocarriers in overcoming MDR are summarized.

Preparation and Drug-Loading Property of Mesoporous Silica Nanoparticles as a Novel Nano-Delivery Vector / 中国药学杂志

OBJECTIVE: To prepare mesoporous silica nanoparticles (MSNs) modified by targeted ingredients to improve the tumor cell lethality of antitumor drugs. METHODS: MSNs were prepared by template-hot water method, and modified with amino group and polyethyleneimine. The nano-carriers were characterized by their morphology, particle size and infrared absorption. Meanwhile, the intracellular uptake and in vitro antitumor activity of MSNs were evaluated on human breast carcinoma cell line (MCF-7). RESUTLS Three kinds of nanoparticles, MSNs, MSNs-NH2 and MSNs-PEI were all spherical, with mean diameters of (65±19), (77±17) and (117±21) nm, respectively. Infrared spectrum and differential thermal analysis RESULTS: indicated that the functional groups were linked onto the surface of MSNs, and slower drug release was observed for MSNs-NH2 and MSNs-PEI. Moreover, the cellular uptake of three nanoparticles were 2.05, 2.89, and 2.63 times higher than free doxorubicin, and the cytotoxicity activity against MCF-7 cells were 1.77, 2.21, and 2.19 times, respectively. CONCLUSION: The preparation method can be used to prepare MSNs nano-carriers. MSNs-NH2 and MSNs-PEI have improved carrier property and antitumor activity.

Advances in the hypoxia-responsive antitumor drug nanocarriers and tumor hypoxia relieve / 中国药科大学学报

Hypoxia,a salient feature of solid tumors,is often associated with invasiveness,metastasis and resistance to anticancer drugs.The strategies including the use of oxygen-carriers based on hyperbaric oxygen and blood substitutes to transport oxygen into tumors or in situ generation of O2from the tumor microenvironment endogenous H2O2have been explored to relieve the tumor hypoxia and to improve therapeutic efficiency.In addi-tion,it is potential to design hypoxia-responsive nanocarriers based on tumor hypoxia microenvironment to deliver anticancer drugs to the targeted tumor site,thereby improve drug concentrations in targeted site,significantly increase the antitumor efficiency and reduce the side-effects of drugs.This review gives an overview of the advances in relieving tumor hypoxia and hypoxia-responsive nanocarriers for tumor to provide a reference for the research and development of new antitumor drugs.

Advances in biodegradable functional polymers based protein drug delivery system / 中国药科大学学报

Biodegradable and biocompatible functional polymers show high potential as novel drug carriers in disease diagnosis and therapy.Recently,protein drugs have brought about major breakthroughs in the treatment of various diseases including cancer,while the development of carrier technology is relatively delayed.This article reviews recent advances in biodegradable functional polymers as protein drug nanocarriers.Additionally,we have discussed the perspective of developing new generations of biocompatible and functional polymers.