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SIRT 1 Activator Loaded Inhaled Antiangiogenic Liposomal Formulation Development for Pulmonary Hypertension

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Abstract

Pulmonary hypertension (PH) is characterized by the rise in mean pulmonary arterial pressure (≥ 20 mmHg at rest) due to the narrowing of the pulmonary arterial networks. Current treatments provide symptomatic treatment and the underlying progress of PH continues leading to higher mortality rates due to non-reversal of the disease. This warrants the need for drug therapies targeting angiogenesis and vascular remodeling mechanisms. Resveratrol, SIRT 1 activator, alters various signaling pathways, inhibits apoptosis, and negatively regulates angiogenesis either by increasing the production of anti-angiogenic factors or inhibiting pro-angiogenic factors. Our work describes the liposomal formulation development, physicochemical characterization, and in vitro aerosolization performance of resveratrol liposomal dry powder formulation. The resveratrol liposomal dry powder formulation reduces the right ventricular systolic pressure measured during right jugular vein catheterization and significantly reverses the PH disease pathological changes as demonstrated by histological observations of pulmonary arterial lumen and ventricular hypertrophy. The developed resveratrol liposomal dry powder formulation alleviates the pulmonary arterial remodeling through its antiangiogenic mechanism and indicates a promising therapeutic strategy for PH treatment.

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Acknowledgements

The authors are thankful to Total Herbs Solution (Mumbai) for providing Resveratrol, Capsugel India Pvt Ltd for providing HPMC capsules (size 3), Lipoid GmbH (Germany) for providing DPPC, and DFE Pharma Ltd for providing Lactohale® 200 and Lactohale® 300 as gift samples. Authors are also thankful to Prof. Sadhana Sathaye for providing the Biopac instrument facility.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (East), Mumbai, 400 019, India

    Sagar Dhoble & Vandana Patravale

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  1. Sagar Dhoble
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  2. Vandana Patravale
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Contributions

All authors contributed to the study’s conception and design. Conceptualization, resources, methodology, formal analysis, data curation, resources, software, and writing—review and editing: Sagar Dhoble. Conceptualization, project administration, supervision, data curation, investigation, validation, and writing—review and editing: Vandana Patravale. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Vandana Patravale.

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The authors have complied with all the ethical standards set by the institutional and national guidelines for the performance of all the animal experiments. The animal studies were performed as per the approved protocols by the Institutional Animal Ethics Committee (IAEC) of the Institute of Chemical Technology (ICT), Mumbai, India, in line with the standards of the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA), India.

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The authors declare no competing interests.

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Dhoble, S., Patravale, V. SIRT 1 Activator Loaded Inhaled Antiangiogenic Liposomal Formulation Development for Pulmonary Hypertension. AAPS PharmSciTech 23, 158 (2022). https://doi.org/10.1208/s12249-022-02312-x

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