Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles

Lee, Changkyu; Seo, Jisoo; Hwang, Ha Shin; Thao, Le Quang; Lee, Seung–Hyun; Lee, Eun Seong; Lee, Eun Hee; Choi, Han‐Gon; Youn, Yu Seok

doi:10.1016/j.biopha.2016.01.027

Cited by 30 publications

(8 citation statements)

References 31 publications

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“…In addition, the selection of suitable anticancer drugs or combination with other bioactive molecules is also expected to improve their antitumor effects. For example, combination with an immunosuppressive reagent (tacrolimus) is expected to suppress lung fibrosis induced by BLM accumulation in lungs [57]. Further investigations must be undertaken for the establishment of efficient cancer chemotherapeutic systems using pH-sensitive polymer–lipid-incorporated liposomes.…”

Section: Resultsmentioning

confidence: 99%

Bleomycin-Loaded pH-Sensitive Polymer–Lipid-Incorporated Liposomes for Cancer Chemotherapy

et al. 2018

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Cancer chemotherapeutic systems with high antitumor effects and less adverse effects are eagerly desired. Here, a pH-sensitive delivery system for bleomycin (BLM) was developed using egg yolk phosphatidylcholine liposomes modified with poly(ethylene glycol)-lipid (PEG-PE) for long circulation in the bloodstream and 2-carboxycyclohexane-1-carboxylated polyglycidol-having distearoyl phosphatidylethanolamine (CHexPG-PE) for pH sensitization. The PEG-PE/CHexPG-PE-introduced liposomes showed content release responding to pH decrease and were taken up by tumor cells at a rate 2.5 times higher than that of liposomes without CHexPG-PE. BLM-loaded PEG-PE/CHexPG-PE-introduced liposomes exhibited comparable cytotoxicity with that of the free drug. Intravenous administration of these liposomes suppressed tumor growth more effectively in tumor-bearing mice than did the free drug and liposomes without CHexPG-PE. However, at a high dosage of BLM, these liposomes showed severe toxicity to the spleen, liver, and lungs, indicating the trapping of liposomes by mononuclear phagocyte systems, probably because of recognition of the carboxylates on the liposomes. An increase in PEG molecular weight on the liposome surface significantly decreased toxicity to the liver and spleen, although toxicity to the lungs remained. Further improvements such as the optimization of PEG density and lipid composition and the introduction of targeting ligands to the liposomes are required to increase therapeutic effects and to reduce adverse effects.

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Section: Resultsmentioning

confidence: 99%

Bleomycin-Loaded pH-Sensitive Polymer–Lipid-Incorporated Liposomes for Cancer Chemotherapy

et al. 2018

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“…Besides, the specific molecular α‐SMA that is a decisive marker for regulating myofibroblast differentiation was a potential target to suppress the development of fibrosis 21,28 . The main reason is that the excessively proliferated myofibroblasts resulted in serious collagen and ECM deposition 32,43 . After silica inducing, α‐SMA expression in model groups was strikingly up‐regulated compared to that in normal groups.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of suppression oxidative stress and inflammation of quercetin by nano‐decoration for ameliorating silica‐induced pulmonary fibrosis

Yao

Meng

et al. 2023

Environmental Toxicology

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Silicosis is a life‐threatening lung fibrotic disease caused by excessive inhalation of environmental exposure to crystalline silica‐containing dust, whereas achieving therapeutic cures are constrained. Antioxidation and anti‐inflammation are currently recognized as effective strategies to counteract organ fibrosis. Using naturally occurring phytomedicines quercetin (Qu) has emerged in antagonizing fibrotic disorders involving oxidative stress and inflammation, but unfortunately the hydrophilicity deficiency. Herein, chitosan‐assisted encapsulation of Qu in nanoparticles (Qu/CS‐NPs) was first fabricated for silicosis‐associated fibrosis treatment by pulmonary delivery. Qu/CS‐NPs with spherical diameters of ~160 nm, demonstrated a high Qu encapsulated capability, excellent hydrophilic stability, fantastic oxidation radical scavenging action, and outstanding controlled as well as slow release Qu action. A silicosis rat model induced by intratracheal instillation silica was established to estimate the anti‐fibrosis effect of Qu/CS‐NPs. After intratracheal administration, CS‐NPs markedly enhanced Qu anti‐fibrotic therapy efficacy, accompanying the evident changes in reducing ROS and MDA production to mitigate oxidative stress, inhibiting IL‐1β and TNF‐α release, improving lung histological architecture, down‐regulating α‐SAM levels and suppressing ECM deposition, and thereby ameliorating silica‐induced pulmonary fibrosis. Results manifested that the augmented antioxidant and anti‐inflammatory activities of Qu by CS‐NPs delivery was a result of achieving this remarkable improvement in curative effects. Combined with negligible systemic toxicity, nano‐decorated Qu may provide a feasible therapeutic option for silicosis therapy.

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“…There have been different types of formulation strategies implemented in the past decade for the improvement of the TAC solubility in the form of self-microemulsifying drug delivery system (SMEDDS), , inclusion complexes, , solid dispersions, − liposomes, and others such as micelles , or nanoparticles. − Also, in 1999, Yura et al synthesized TAC-dextran bioconjugate with 0.45% drug loading and utilized a radioactive element to track the drug . Also, acid-responsive prodrugs have been synthesized earlier for anticancer drug delivery. − Compared to previous investigations, we have synthesized acid-cleavable HA-ADH-TAC conjugate in our study with improved drug loading, better in vitro sustained drug release, and improved half-life.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid-Tacrolimus Bioconjugate: Synthesis, Characterization, and Pharmacokinetic Investigation of an Acid-Responsive Macromolecular Prodrug

Dheer

Gupta

Singh

et al. 2019

ACS Appl. Bio Mater.

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Polymer-drug conjugates have been the cornerstone of several drug delivery systems owing to their numerous benefits such as improved drug solubilization, controlled release, increased efficacy, and improved pharmacokinetics. Herein, an acid-responsive macromolecular prodrug was synthesized by conjugation of Tacrolimus (TAC; FK506) with chemically modified hyaluronic acid (HA), and its physicochemical and pharmacokinetic properties were studied in detail. The prepared conjugate (HA-ADH-TAC) showed 1% drug loading, sustained drug release, and significantly enhanced solubility for the investigated drug. Additionally, cellular uptake study indicated augmented uptake of this conjugate, and hemolysis assay showed biocompatibility of the developed prodrug. Further, the pharmacokinetic behavior of the conjugate was investigated, and it was observed that pharmacokinetic parameters with the conjugate were improved. The results indicate that the developed HA-tacrolimus conjugate has the edge over the plain drug in terms of improved physicochemical properties and favorable pharmacokinetic response.

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Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles

Cited by 30 publications

References 31 publications

Bleomycin-Loaded pH-Sensitive Polymer–Lipid-Incorporated Liposomes for Cancer Chemotherapy

Bleomycin-Loaded pH-Sensitive Polymer–Lipid-Incorporated Liposomes for Cancer Chemotherapy

Enhancement of suppression oxidative stress and inflammation of quercetin by nano‐decoration for ameliorating silica‐induced pulmonary fibrosis

Hyaluronic Acid-Tacrolimus Bioconjugate: Synthesis, Characterization, and Pharmacokinetic Investigation of an Acid-Responsive Macromolecular Prodrug

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