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Design, Development, and In Vitro Characterization of Pirfenidone-Loaded Biodegradable Nanoparticles for Idiopathic Pulmonary Fibrosis

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Abstract

Purpose

The purpose of this study was to develop inhalable pirfenidone (PFD) nanoparticles for the delivery of the medicine to specific alveolar epithelial cells (AECs) in the idiopathic pulmonary fibrosis (IPF) treatment. PFD has major problems like low oral route absorption due to the presence of food, faster elimination half-life, and potent phototoxicity. PFD-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles provide enhanced release of drug and reduce its toxicity, dose, and dosing frequency by targeting the AECs.

Methods

The PFD-loaded PLGA NPs were prepared by a single emulsion solvent evaporation method. The preliminary studies were carried out with process parameters like the selection of organic phase, effect of organic phase volume, effect of stabilizer (PVA) concentration, drug:polymer ratio, and sonication time. The effects of two formulation variables including the drug:polymer ratio and surfactant concentration were examined by using 32 full factorial design applied to get optimized formulation. The final product was lyophilized and made free-flowing powder formulation for pulmonary administration.

Results

Optimized PFD-loaded PLGA NPs showed initial burst release followed by sustained up to 71.19 ± 5.39% at 24 h. The particle size, polydispersity index, zeta potential, and % entrapment efficiency were found to be 523 ± 6.42 nm, 0.183 ± 0.011, 1.62 ± 0.22 mV, and 44.14 ± 3.74% respectively.

Conclusions

There was no significant aggregation of PFD-loaded PLGA NPs during 6 months of stability study and spherical shape nanoparticle with smooth surface as per SEM study. Hence, PFD-loaded PLGA NPs can be a suitable alternative to the currently available therapy.

Graphical Abstract

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Data Availability

All data and material are available upon request. Data attached as supplimentary material too.

Abbreviations

AECs:

Alveolar epithelial cells

ANOVA:

Analysis of variance

DCM:

Dichloromethane

DoE:

Design of the experiment

DSC:

Differential scanning calorimetry

EE:

Entrapment efficiency

FDA:

Food and Drug Administration

FTIR:

Fourier transform infrared spectroscopy

GSD:

Geometric standard deviation

IPF:

Idiopathic pulmonary fibrosis

MMAD:

Mass median aerodynamic diameter

NPs:

Nanoparticles

PFD:

Pirfenidone

PLGA:

Poly(D,L-lactic-co-glycolic acid)

PVA:

Polyvinyl alcohol

PI:

Polydispersity index

SEM:

Scanning electron microscopy

TNF-α:

Tumor necrosis factor-α

TGF-β:

Transforming growth factor-β

ZP:

Zeta potential

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Acknowledgements

The authors would like to thank Dr. Praful Bharadiya and Dr. Mihir Raval for their helpful comments. The authors are also thankful to Meck Pharmaceuticals & Chemicals Private Limited and ZCL Chemicals Ltd., Gujarat, India, for providing respective gift samples.

Funding

The Department of Technical Education, Government of Gujarat, India, provided the financial assistance (minor research grant) provided under the SSIP (Student Startup & Innovation Policy) scheme and KS Patel Centre for Entrepreneurship, RK University, for this project.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, RK University, Rajkot, Gujarat, 360020, India

    Kiran R. Dudhat

  2. Gujarat Technological University, Chandkheda, Gujarat, India

    Kiran R. Dudhat

  3. Indukaka Ipcowala College of Pharmacy, Gujarat Technological University, New Vallabh Vidyanagar, Anand, Gujarat, 388121, India

    Harsha V. Patel

  4. B. K. Mody Government Pharmacy College, Gujarat Technological University, Rajkot, Gujarat, 360004, India

    Dhaval D. Mori

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Contributions

The authors Ms. Kiran Dudhat and Dr. Harsha Patel are considerably subsidized to the writing of this research article. Ms. Kiran Dudhat, who is the first author, has played a critical part in this article. Development, design, and evaluation of the PFD-loaded PLGA nanoparticles were by her. Dr. Harsha Patel and Dr. Dhaval Mori provided guidance and reviewed the article judgmentally for its knowledgeable content and assisted in the concluding endorsement of the version to be published.

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Correspondence to Kiran R. Dudhat.

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Dudhat, K.R., Patel, H.V. & Mori, D.D. Design, Development, and In Vitro Characterization of Pirfenidone-Loaded Biodegradable Nanoparticles for Idiopathic Pulmonary Fibrosis. J Pharm Innov 18, 1908–1925 (2023). https://doi.org/10.1007/s12247-023-09763-0

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