Inhaled deep eutectic solvent based-nanoemulsion of pirfenidone in idiopathic pulmonary fibrosis

Kang, Ji‐Houn; Yang, Min-Seok; Kwon, Taek Kwan; Kim, Dong-Wook; Park, Chun‐Woong

doi:10.1016/j.jconrel.2022.10.045

Cited by 15 publications

(4 citation statements)

References 84 publications

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“…Notably, pirfenidone and nintedanib have been recommended by guidelines for the treatment of IPF. However, their effectiveness and safety have not been clearly defined, and they have some side effects . As shown in the results of this study for monitoring the survival status of mice, the three-week treatment with pirfenidone significantly reduced body weight and even led to increased mortality in mice, which is in contrast to the RLX-free treatment group’s anti-fibrotic properties.…”

Section: Discussionmentioning

confidence: 99%

“…However, their effectiveness and safety have not been clearly defined, and they have some side effects. 48 As shown in the results of this study for monitoring the survival status of mice, the three-week treatment with pirfenidone significantly reduced body weight and even led to increased mortality in mice, which is in contrast to the RLX-free treatment group's anti-fibrotic properties. RLX was inhaled via the respiratory tract using porous microspheres as a drug delivery system, which allowed for long-term slow release and improved deposition efficiency.…”

Section: Discussionmentioning

confidence: 99%

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Relaxin-Loaded Inhaled Porous Microspheres Inhibit Idiopathic Pulmonary Fibrosis and Improve Pulmonary Function Post-Bleomycin Challenges

Qiu

Shi

et al. 2023

Mol. Pharmaceutics

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Idiopathic pulmonary fibrosis (IPF) causes worsening pulmonary function, and no effective treatment for the disease etiology is available now. Recombinant Human Relaxin-2 (RLX), a peptide agent with anti-remodeling and anti-fibrotic effects, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, due to its short circulating half-life, optimal efficacy requires continuous infusion or repeated injections. Here, we developed the porous microspheres loading RLX (RLX@PMs) and evaluated their therapeutic potential on IPF by aerosol inhalation. RLX@PMs have a large geometric diameter as RLX reservoirs for a longterm drug release, but smaller aerodynamic diameter due to their porous structures, which were beneficial for higher deposition in the deeper lungs. The results showed a prolonged release over 24 days, and the released drug maintained its peptide structure and activity. RLX@PMs protected mice from excessive collagen deposition, architectural distortion, and decreased compliance after a single inhalation administration in the bleomycin-induced pulmonary fibrosis model. Moreover, RLX@PMs showed better safety than frequent gavage administration of pirfenidone. We also found RLX-ameliorated human myofibroblastinduced collagen gel contraction and suppressed macrophage polarization to the M2 type, which may be the reason for reversing fibrosis. Hence, RLX@PMs represent a novel strategy for the treatment of IPF and suggest clinical translational potential.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relaxin-Loaded Inhaled Porous Microspheres Inhibit Idiopathic Pulmonary Fibrosis and Improve Pulmonary Function Post-Bleomycin Challenges

Qiu

Shi

et al. 2023

Mol. Pharmaceutics

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“…An anti-fibrotic drug known as pirfenidone (PFD) is prescribed for the management of idiopathic pulmonary fibrosis (IPF). 12 , 13 PFD possesses anti-inflammatory, anti-fibrotic, and antioxidant functions in different animal models. In addition, in the context of tumor therapy, PFD is proven to be effective in suppressing TGF-β expression, thereby suppressing the activation of CAFs and the production of collagen, consequently impeding tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer

Zhou,

Du,

Jia

et al. 2024

Sig Transduct Target Ther

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Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for it. The tumor microenvironment (TME) in pancreatic cancer, distinguished by fibrosis and the existence of cancer-associated fibroblasts (CAFs), exerts a pivotal influence on both tumor advancement and resistance to therapy. Recent advancements in the field of engineered extracellular vesicles (EVs) offer novel avenues for targeted therapy in pancreatic cancer. This study aimed to develop engineered EVs for the targeted reprogramming of CAFs and modulating the TME in pancreatic cancer. EVs obtained from bone marrow mesenchymal stem cells (BMSCs) were loaded with miR-138-5p and the anti-fibrotic agent pirfenidone (PFD) and subjected to surface modification with integrin α5-targeting peptides (named IEVs-PFD/138) to reprogram CAFs and suppress their pro-tumorigenic effects. Integrin α5-targeting peptide modification enhanced the CAF-targeting ability of EVs. miR-138-5p directly inhibited the formation of the FERMT2-TGFBR1 complex, inhibiting TGF-β signaling pathway activation. In addition, miR-138-5p inhibited proline-mediated collagen synthesis by directly targeting the FERMT2-PYCR1 complex. The combination of miR-138-5p and PFD in EVs synergistically promoted CAF reprogramming and suppressed the pro-cancer effects of CAFs. Preclinical experiments using the orthotopic stroma-rich and patient-derived xenograft mouse models yielded promising results. In particular, IEVs-PFD/138 effectively reprogrammed CAFs and remodeled TME, which resulted in decreased tumor pressure, enhanced gemcitabine perfusion, tumor hypoxia amelioration, and greater sensitivity of cancer cells to chemotherapy. Thus, the strategy developed in this study can improve chemotherapy outcomes. Utilizing IEVs-PFD/138 as a targeted therapeutic agent to modulate CAFs and the TME represents a promising therapeutic approach for pancreatic cancer.

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“…It is an emerging practice to improve solubility and dissolution of pharmaceutical active agents. , A eutectic mixture is a composition of two or more components that displays the minimum freezing point among all possible mixtures of these components. − A eutectic mixture containing drug–drug, drug–excipient, or excipient–excipient contents may inhibit each other’s crystallization process, resulting in a lower melting point than either separated component . In a simpler description, eutectic systems may result in a liquid formation upon mixing the two solids (known as the liquefaction effect), which is a crucial phenomenon in pharmaceutical compounding, formulation, stability, and manufacturing. − To illustrate these points, eutectic mixtures are reported to increase drug solubility, dissolution, permeation, and bioavailability. − …”

Section: Introductionmentioning

confidence: 99%

Eutectics in Pharmacy Curriculum: A Simple Demonstration with Pharmaceutical Relevance

Daou,

Arakkal,

Alkilany

2023

J. Chem. Educ.

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In chemistry, a eutectic mixture refers to a mixture of two or more components at which the lowest possible freezing point is observed. This phenomenon is covered in a wide range of curricula such as physics, chemistry, chemical engineering, and pharmacy to various depths. Despite the significance of this phenomenon in pharmaceutical compounding and formulation, standard pharmacy curricula provide only limited coverage of the eutectic mixture and the theoretical aspects associated with its phase diagram. A practical session on a eutectic mixture should augment the theoretical pedagogical component and enable a more profound understanding. Despite the existence of educational publications that discuss this phenomenon from a chemical perspective, there is currently no reported experimental laboratory specifically focused on the eutectic phenomenon and its implications in the field of pharmacy. In this study, we employ camphor and menthol as pharmaceutical active ingredients that illustrate a robust eutectic phenomenon within practical temperature ranges. Moreover, we utilize the eutectic phenomenon and the resulting liquefaction effect upon mixing camphor and menthol to prepare semisolid pharmaceutical dosage forms (gels and rubs), demonstrating to students the impact of this phenomenon in drug compounding and formulation.

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Inhaled deep eutectic solvent based-nanoemulsion of pirfenidone in idiopathic pulmonary fibrosis

Cited by 15 publications

References 84 publications

Relaxin-Loaded Inhaled Porous Microspheres Inhibit Idiopathic Pulmonary Fibrosis and Improve Pulmonary Function Post-Bleomycin Challenges

Relaxin-Loaded Inhaled Porous Microspheres Inhibit Idiopathic Pulmonary Fibrosis and Improve Pulmonary Function Post-Bleomycin Challenges

Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer

Eutectics in Pharmacy Curriculum: A Simple Demonstration with Pharmaceutical Relevance

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