Preparation of novel pirfenidone microspheres for lung-targeted delivery: in vitro and in vivo study

Li, Dianbo; Gong, Lidong

doi:10.2147/dddt.s113670

Cited by 11 publications

(2 citation statements)

References 23 publications

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“…PF has been used in animal models for treating chronic hepatitis C, hypertrophic cardiomyopathy and fibrotic renal disorders 28–30. PF can be administered intratracheally, orally and intravenously as microspheres, aerosols, and liposomes respectively 31–33. Clinically, PF has been used for the treatment of lung fibrosis 34,35.…”

Section: Introductionmentioning

confidence: 99%

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFβ-induced HSC-T6 cells activation</p>

Ullah

Oupický

2019

IJN

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Background: Liver fibrosis is a chronic liver disease associated with an excessive accumulation of extracellualr matrix (ECM) proteins which ultimately lead to cirrohosis and hepatocellular carcinoma. Purpose: Liver fibrosis therapies that use combination approaches with the ability to affect multiple disease pathways have proven higher efficacies. This study aimed at optimizing and characterizing the co-encapsulation of pirfenidone (PF) and AMD3100 (AMD) into CXCR4-targeted combination liposomes (CTC liposome) for CXCR4 targeting, and the inhibition of major molecular culprits ie α-SMA, CXCR4, TGFβ, and P-p38 involved in liver fibrosis in-vitro. Methods: The CTC liposomes were prepared using the thin-film hydration method. The concentration of encapsulated AMD and PF was measured by HPLC and UV spectrophotometry, respectively. Tramsmission electron microscopy (TEM) was used to determine the liposomal morphology. The CXCR4 targeting ability was determined by CXCR4 redistribution assay. Confocal microscopy and flowcytometry were used to determine the CXCR4 mediated cell uptake. The apoptosis inducing and protein downreguating ability of CTC liposomes were determined by apoptosis assay and western blot analysis, respectively. In-vivo biodistribution and Hoechst staining were used to confirm the feasibility of CTC liposome for the in-vivo applications and drug targeted accumulation, respectively. Results: The TEM studies revealed that CTC liposomes were spherical in shape. The cumulative release of AMD and PF from CTC liposome was 67% and 84%, respectively, at 48 h. Compared to the free drug counterparts, encapsulated drugs displayed higher cell viability. The CXCR4 redistribution assay confirmed the CXCR4 targeting and antagonistic ability of CTC liposomes. The CTC liposomes were internalized more effectively via caveolae-mediated endocytic pathways. CTC liposomes displayed aggressive apoptosis (87.3%) in TGFβ-induced activated HSC-T6 cells suggesting a propensity to fibrosis regression. Also, CTC liposomes significantly reduced α-SMA (65%), CXCR4 (77%), TGFβ (89%), and P-p38 (66%) expressions, better than free drugs. CTC@IR780 liposomes (CTC liposomes incorporating IR780 dye) were more accumulated in fibrotic livers compared to free IR780, as judged by in-vivo imaging, biodistribution analysis, and Hoechst staining. These findings suggest that this simple and stable CTC liposomal system holds a great promise for the treatment and prevention of liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFβ-induced HSC-T6 cells activation</p>

Ullah

Oupický

2019

IJN

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“…This has enabled the long term use of a drug class that otherwise would have 4 elicited severe adverse effects by systemic dosing. Pulmonary administration has been studied and proposed also for the currently used IPF drug pirfenidone (12,30,38,43) and N-acetylcysteine (7,31).…”

mentioning

confidence: 99%

Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice

Vartiainen

Raula

Bimbo

et al. 2018

International Journal of Pharmaceutics

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The aim of this work was to study the antifibrotic effect of pulmonary administration of tilorone to lung fibrosis. L-leucine coated tilorone particles were prepared and their aerosolization properties were analyzed using two dry powder inhalers (Easyhaler and Twister). In addition, the biological activity and cell monolayer permeation was tested. The antifibrotic effect of tilorone delivered by oropharyngeal aspiration was studied in vivo using a silica-induced model of pulmonary fibrosis in mice in a preventive setting. When delivered from the Easyhaler in an inhalation simulator, the emitted dose and fine particle fraction were independent from the pressure applied and showed dose repeatability. However, with Twister the aerosolization was pressure-dependent indicating poor compatibility between the device and the formulation. The formulation showed more consistent permeation through a differentiated Calu-3 cell monolayer compared to pristine tilorone. Tilorone decreased the histological fibrosis score in vivo in systemic and local administration, but only systemic administration decreased the mRNA expression of type I collagen. The difference was hypothesized to result from 40-fold higher drug concentration in tissue samples in the systemic administration group. These results show that tilorone can be formulated as inhalable dry powder and has potential as an oral and inhalable antifibrotic drug.

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Pulmonary Targeting Crosslinked Cyclodextrin Metal–Organic Frameworks for Lung Cancer Therapy

Xiong

et al. 2020

Adv Funct Materials

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Lung cancer is a serious threat to human health with the highest morbidity and mortality; metastatic lung cancer accounts for a majority of cancerrelated deaths. Hence, there is considerable interest in developing efficient lung-targeted drug delivery systems to improve overall survival and quality of life of lung cancer patients. Based on the lung-targeting characteristics of cubic crosslinked cyclodextrin metal-organic framework (CDF) nanoparticles, this study shows the synthesis of a nanoplatform using RGD-functionalized CDF to co-deliver low-molecular-weight heparin (LMWH) and doxorubicin (DOX) for treatment of lung cancer. Rational design of the DOX-loaded RGD-CDF-LMWH nanoplatform (RCLD) is carried out. RCLD nanoparticles are efficiently targeted to lung tumors following intravenous administration; RCLD accumulation in the lung is 5.8 times greater than that in the liver. Moreover, RCLD inhibits migration and invasion of cancer cells in vitro and significantly diminishes lung tumor nodule count and area of spread in human A549 and murine B16F10 lung cancer models in vivo. Furthermore, RCLD does not show serum enzyme or histopathologic indicators of tissue damage or adverse hematologic effects. Therefore, the multiple antitumor activities of this novel RCLD nanoplatform, alongside its safety profile for normal tissues, strongly support its use for targeted treatment of lung cancer.

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Preparation of novel pirfenidone microspheres for lung-targeted delivery: in vitro and in vivo study

Cited by 11 publications

References 23 publications

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFβ-induced HSC-T6 cells activation</p>

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFβ-induced HSC-T6 cells activation</p>

Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice

Pulmonary Targeting Crosslinked Cyclodextrin Metal–Organic Frameworks for Lung Cancer Therapy

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Preparation of novel pirfenidone microspheres for lung-targeted delivery: in vitro and in vivo study

Cited by 11 publications

References 23 publications

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGF&beta;-induced HSC-T6 cells activation</p>

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGF&beta;-induced HSC-T6 cells activation</p>

Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice

Pulmonary Targeting Crosslinked Cyclodextrin Metal–Organic Frameworks for Lung Cancer Therapy

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Product

Resources

About

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFβ-induced HSC-T6 cells activation</p>

<p>CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFβ-induced HSC-T6 cells activation</p>