Targeted Therapeutic Effect of Bavachinin Nanospheres on Pathological Site of Chronic Asthmatic Mice Model

2021 ◽  
Vol 21 (2) ◽  
pp. 1085-1090
Author(s):  
Chunxia Zhang ◽  
Qian Qin ◽  
Hongle Li
Keyword(s):  
Therapeutic Effect ◽  
Lung Tissue ◽  
Infrared Imaging ◽  
Oral Drug Delivery ◽  
Inflammatory Cells ◽  
Good Effect ◽  
Oral Drug ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Imaging Results

Steroids are the main drugs currently used to treat asthma. However, the toxic and side effects of these drugs and the tolerance of the drugs due to long-term administration are still problems in the clinical treatment of asthma. Bavachinin has a good effect in the treatment of mouse asthma models, and it can effectively inhibit the expression of a variety of cytokines. However, it is extremely difficult to dissolve in water, has low bioavailability, and is quickly cleared in the blood. These characteristics limit its clinical application potential. In this study, nanotechnology was used to construct an effective oral drug delivery system. Through analysis of serum-related antibodies and cytokines, the system showed significant therapeutic effects on asthma-positive groups. Far-infrared imaging results showed that the system has a good targeted enrichment effect on pathological parts, while showing lower toxicity and higher therapeutic effect. Whether it is the splenocyte flow typing or the analysis of lung tissue, the system has verified the excellent treatment, and through the observation of paraffin sections of lung tissue, it was found that the bronchial morphology returned to normal after drug treatment, and the leakage of inflammatory cells was significantly reduced.

scholarly journals Polymeric micelles for oral drug delivery: Why and how

2004 ◽  
Vol 76 (7-8) ◽  
pp. 1321-1335 ◽  
Author(s):  
M. F. Francis ◽  
Mariana Cristea ◽  
F. M. Winnik
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Polymeric Micelles ◽  
Oral Drug Delivery ◽  
Polymeric Micelle ◽  
Water Soluble ◽  
Oral Drug ◽  
Therapeutic Effects ◽  
The Impact

The oral delivery of drugs is regarded as the optimal means for achieving therapeutic effects owing to increased patient compliance. Unfortunately, the oral delivery route is beset with problems such as gastrointestinal (GI) destruction of labile molecules, low levels of macromolecular absorption, etc. To reduce the impact of digestive enzymes and to ensure the absorption of bioactive agents in an unaltered form, molecules may be incorporated into microparticulate carriers. Many approaches to achieve the oral absorption of a wide variety of drugs are currently under investigation. Among the different polymer-based drug delivery systems, polymeric micelles represent a promising delivery vehicle especially intended for poorly water-soluble pharmaceutical active ingredients in order to improve their oral bioavailability. Recent findings of a dextran-based polymeric micelle study for solubilization of a highly lipophilic drug, cyclosporin A (CsA), will be discussed.

scholarly journals Allergen specific Treg upregulated by lung-stage schistosome infection alleviates allergic airway inflammation via inhibiting IgE secretion

2020 ◽  
Author(s):  
Zhi dan Li ◽  
Wei Zhang ◽  
fang Luo ◽  
jian Li ◽  
Wen bin Yang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Therapeutic Effect ◽  
Lung Tissue ◽  
Allergic Airway Inflammation ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Schistosome Infection ◽  
Allergen Sensitization ◽  
Asthma Attack

Schistosome infection showed protective effects against allergic airway inflammation (AAI). However,controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. Moreover, most previous studies focused on understanding the preventive effect of schistosome infection on asthma (infection before allergen sensitization), while its therapeutic effects (infection after allergen sensitization) were rarely investigated. In this study, we investigated the therapeutic effects of schistosome infection on AAI using a mouse model of OVA induced asthma. To explore how the timing of schistosome infection influences its therapeutic effect, the mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day before OVA induced asthma attack (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage schistosome infection could relieve OVA induced asthma in a mouse model. The therapeutic effect was mediated by the upregulated OVA specific Treg which suppressed IgE production and Th2 cytokine secretion. Our results may facilitate the discovery of a new therapy for AAI.

scholarly journals Treatment of the bone marrow stromal stem cell supernatant by nasal administration—a new approach to EAE therapy

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xi Wang ◽  
Wantong Zhai ◽  
Jiahui Zhu ◽  
Wei Zhao ◽  
Xiaoyi Zou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Therapeutic Effect ◽  
Inflammatory Cells ◽  
Nasal Administration ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
The Central Nervous System ◽  
Functional Features

Abstract Introduction Multiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS). CNS has its own unique structural and functional features, while the lack of precision regulatory element with high specificity as therapeutic targets makes the development of disease treatment in the bottleneck. Recently, the immunomodulation and neuroprotection capabilities of bone marrow stromal stem cells (BMSCs) were shown in experimental autoimmune encephalomyelitis (EAE). However, the administration route and the safety evaluation limit the application of BMSC. In this study, we investigated the therapeutic effect of BMSC supernatant by nasal administration. Methods In the basis of the establishment of the EAE model, the BMSC supernatant were treated by nasal administration. The clinical score and weight were used to determine the therapeutic effect. The demyelination of the spinal cord was detected by LFB staining. ELISA was used to detect the expression of inflammatory factors in serum of peripheral blood. Flow cytometry was performed to detect pro-inflammatory cells in the spleen and draining lymph nodes. Results BMSC supernatant by nasal administration can alleviate B cell-mediated clinical symptoms of EAE, decrease the degree of demyelination, and reduce the inflammatory cells infiltrated into the central nervous system; lessen the antibody titer in peripheral bloods; and significantly lower the expression of inflammatory factors. As a new, non-invasive treatment, there are no differences in the therapeutic effects between BMSC supernatant treated by nasal route and the conventional applications, i.e. intraperitoneal or intravenous injection. Conclusions BMSC supernatant administered via the nasal cavity provide new sights and new ways for the EAE therapy.

scholarly journals Allergen Specific Treg Upregulated by Lung-stage Schistosome Infection Alleviates Allergic Airway Inflammation via Inhibiting IgE Secretion

2020 ◽  
Author(s):  
Zhi dan Li ◽  
Wei Zhang ◽  
Fang Luo ◽  
Jian Li ◽  
Wen bin Yang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Therapeutic Effect ◽  
Lung Tissue ◽  
Allergic Airway Inflammation ◽  
Specific Ige ◽  
Therapeutic Effects ◽  
Lung Pathology ◽  
Protective Effects ◽  
Schistosome Infection

Abstract Background. Schistosome infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist regarding the timing of helminth infection and the underlying mechanisms. Moreover, the therapeutic effects of schistosome infection on asthma were rarely investigated. Methods. The mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). Lung pathology, inflammatory cytokines, IgE and frequency of Treg were measured to evaluate the therapeutic effect. The modulation of allergen specific Treg were elucidated by adoptive transfer and Treg deletion in vivo. Finally, RNAseq was employed to explore the key molecules and pathways that might contribute to Treg upregulation. Results. We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. Conclusions. Our results proved that lung-stage schistosome infection could relieve OVA induced AAI in mouse model by the upregulated OVA specific Treg, which may facilitate the discovery of a new therapy for asthma.

scholarly journals Nanocomposites-Based Targeted Oral Drug Delivery Systems with Infliximab in a Murine Colitis Model

2020 ◽  
Author(s):  
Jung Min Kim ◽  
Da Hye Kim ◽  
Hyo Jeong Park ◽  
Hyun Woo Ma ◽  
I Seul Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Oral Drug Delivery ◽  
Systemic Exposure ◽  
Treated Group ◽  
Delivery Systems ◽  
Oral Drug ◽  
Therapeutic Effects ◽  
Murine Colitis ◽  
Promising Therapeutic Approach

Abstract Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. We developed a colon-specific drug delivery system for the oral administration of IFX using ternary nanocomposite carriers. Nanocomposite carriers consisting of liposomes, aminoclay-coated liposomes (AC-L), Eudragit S100 AC-L (EAC-L) or those carrying IFX (IFX-L, AC-IFX-L, and EAC-IFX-L) were orally administered to mice with dextran sulfate sodium-induced colitis. We evaluated the effects of nanocomposite carriers on lymphocytes and monocytes in peripheral blood mononuclear cells (PBMC) of IBD patients. We studied the therapeutic effects of the nanocomposites themselves and nanocomposites with IFX at target sites in vivo and in vitro . All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions ( Tnfa , Il1b , and Il17 ). We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.

scholarly journals Essential Oil-Rich Chinese Formula Luofushan-Baicao Oil Inhibits the Infection of Influenza A Virus through the Regulation of NF-κB P65 and IRF3 Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xin Mao ◽  
Shuyin Gu ◽  
Huiting Sang ◽  
Yilu Ye ◽  
Jingyan Li ◽  
...  
Keyword(s):  
Essential Oil ◽  
Influenza A Virus ◽  
Lung Tissue ◽  
Viral Protein ◽  
Influenza A ◽  
Poly I:C ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Polycytidylic Acid

Background. Luofushan-Baicao Oil (LBO) is an essential oil-rich traditional Chinese medicine (TCM) formula that is commonly used to treat cold, cough, headache, sore throat, swelling, and pain. However, the anti-influenza activities of LBO and the underlying mechanism remain to be investigated. Methods. The in vitro anti-influenza activity of LBO was tested with methyl thiazolyl tetrazolium (MTT) and plaque assays. The effects of LBO on the expressions of viral nucleoprotein and cytokines were evaluated. In the polyinosinic-polycytidylic acid- (Poly I: C-) induced inflammation model, the influences of LBO on the expression of cytokines and the activation of NF-κB P65 (P65) and interferon regulatory factor 3 (IRF3) were tested. After influenza A virus (IVA) infection, mice were administered with LBO for 5 days. The lung index, histopathologic change, the expression of viral protein, P65, and IRF3 in the lung tissue were measured. The levels of proinflammatory cytokines in serum were examined. Results. In vitro, LBO could significantly inhibit the infection of IVA, decrease the formation of plaques, and reduce the expression of viral nucleoprotein and cytokines. LBO could also effectively downregulate the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and interferon-β and the activation of P65 and IRF3 in Poly I:C-treated cells. In the IVA-infected mice model, inhalation of LBO with atomizer could decrease the lung index, alleviate the pathological injury in the lung tissue, and reduce the serum levels of IL-1β and IL-6. LBO could significantly downregulate the expression of viral protein (nucleoprotein, PB2, and matrix 2 ion channel) and the phosphorylation of P65 and IRF3 in the lungs of mice. Conclusion. The therapeutic effects of LBO on treating influenza might result from the regulation of the immune response of IVA infection. LBO can be developed as an alternative therapeutic agent for influenza prevention.

scholarly journals Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Kai Wang ◽  
Boxiang Du ◽  
Yan Zhang ◽  
Congyou Wu ◽  
Xiuli Wang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Lung Tissue ◽  
Gene Knockout ◽  
Inflammatory Factors ◽  
Mouse Lung ◽  
Therapeutic Effects ◽  
Proliferation And Differentiation ◽  
Differentiation Status ◽  
Mouse Lung Tissue ◽  
Vimentin Gene

Acute respiratory distress syndrome (ARDS) is difficult to treat and has a high mortality rate. Mesenchymal stem cells (MSCs) have an important therapeutic effect in ARDS. While the mechanism of MSC migration to the lungs remains unclear, the role of MSCs is of great clinical significance. To this end, we constructed vimentin knockout mice, extracted bone MSCs from the mice, and used them for the treatment of LPS-induced ARDS. H&E staining and Masson staining of mouse lung tissue allowed us to assess the degree of damage and fibrosis of mouse lung tissue. By measuring serum TNF-α, TGF-β, and INF-γ, we were able to monitor the release of inflammatory factors. Finally, through immunoprecipitation and gene knockout experiments, we identified upstream molecules that regulate vimentin and elucidated the mechanism that mediates MSC migration. As a result, we found that MSCs from wild-type mice can significantly alleviate ARDS and reduce lung inflammation, while vimentin gene knockout reduced the therapeutic effect of MSCs in ARDS. Cytological experiments showed that vimentin gene knockout can significantly inhibit the migration of MSCs and showed that it changes the proliferation and differentiation status of MSCs. Further experiments found that vimentin’s regulation of MSC migration is mainly mediated by Rab7a. Rab7a knockout blocked the migration of MSCs and weakened the therapeutic effect of MSCs in ARDS. In conclusion, we have shown that the Vimentin-Rab7a pathway mediates migration of MSCs and leads to therapeutic effects in ARDS.

Applications of Ion Exchange Resin in Oral Drug Delivery Systems

2017 ◽  
Vol 7 (03) ◽  
Author(s):  
Kathpalia Harsha ◽  
Das Sukanya
Keyword(s):  
Drug Delivery ◽  
Ion Exchange ◽  
Drug Delivery Systems ◽  
Oral Drug Delivery ◽  
Physical Stability ◽  
Delivery Systems ◽  
Oral Drug ◽  
Ion Exchange Resins ◽  
Exchange Resins ◽  
Oral Drug Delivery Systems

Ion Exchange Resins (IER) are insoluble polymers having styrene divinylbenzene copolymer backbone that contain acidic or basic functional groups and have the ability to exchange counter ions with the surrounding aqueous solutions. From the past many years they have been widely used for purification and softening of water and in chromatographic columns, however recently their use in pharmaceutical industry has gained considerable importance. Due to the physical stability and inert nature of the resins, they can be used as a versatile vehicle to design several modified release dosage forms The ionizable drug is complexed with the resin owing to the property of ion exchange. This resin complex dissociatesin vivo to release the drug. Based on the dissociation strength of the drug from the drug resin complex, various release patterns can be achieved. Many formulation glitches can be circumvented using ion exchange resins such as bitter taste and deliquescence. These resins also aid in enhancing disintegrationand stability of formulation. This review focuses on different types of ion exchange resins, their preparation methods, chemistry, properties, incompatibilities and their application in various oral drug delivery systems as well as highlighting their use as therapeutic agents.

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