Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation.
Inflammation
Microparticles
Nanoparticles
Pulmonary administration
Rapamycin
Journal
Drug delivery and translational research
ISSN: 2190-3948
Titre abrégé: Drug Deliv Transl Res
Pays: United States
ID NLM: 101540061
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
accepted:
29
11
2021
pubmed:
20
2
2022
medline:
2
7
2022
entrez:
19
2
2022
Statut:
ppublish
Résumé
It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Nevertheless, Rapa clinical application is still prevented by its unfavorable chemical-physical properties, limited oral bioavailability, and adverse effects related to non-specific biodistribution. In this paper, the design and production of a novel formulation of Rapa based on nano into micro (NiM) particles are detailed. To achieve it, Rapa-loaded nanoparticles were produced by nanoprecipitation of an amphiphilic pegylated poly-ɛ-caprolactone/polyhydroxyethyl aspartamide graft copolymer. The obtained nanoparticles that showed a drug loading of 14.4 wt% (corresponding to an encapsulation efficiency of 82 wt%) did not interact with mucins and were able to release and protect Rapa from degradation in simulated lung and cell fluids. To allow their local administration to the lungs as a dry powder, particle engineering at micro-sized level was done by embedding nanoparticles into mannitol-based microparticles by spray drying. Obtained NiM particles had a mean diameter of about 2-µ, spherical shape and had good potential to be delivered to the lungs by a breath-activated dry powder inhalers. Rheological and turbidity experiments showed that these NiM particles can dissolve in lung simulated fluid and deliver the Rapa-loaded pegylated nanoparticles, which can diffuse through the mucus layer.
Identifiants
pubmed: 35182368
doi: 10.1007/s13346-021-01102-5
pii: 10.1007/s13346-021-01102-5
pmc: PMC8857397
doi:
Substances chimiques
Powders
0
Polyethylene Glycols
3WJQ0SDW1A
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1859-1872Informations de copyright
© 2022. The Author(s).
Références
Racanelli AC, Kikkers SA, Choi AMK, Cloonan SM. Autophagy and inflammation in chronic respiratory disease. Autophagy. 2018;14:221–32.
doi: 10.1080/15548627.2017.1389823
Thakur AK, Chellappan DK, Dua K, Mehta M, Satija S, Singh I. Patented therapeutic drug delivery strategies for targeting pulmonary diseases. Expert Opin Ther Pat Taylor & Francis. 2020;0:1.
Pulivendala G, Bale S, Godugu C. Inhalation of sustained release microparticles for the targeted treatment of respiratory diseases. Drug Deliv. Transl. Res. 2020;10:339–53.
Wang H, Wu L, Sun X. Intratracheal delivery of nano- and microparticles and hyperpolarized gases: a promising strategy for the imaging and treatment of respiratory disease. Chest Elsevier Inc. 2020;157:1579–90.
Beck-Broichsitter M, Merkel OM, Kissel T. Controlled pulmonary drug and gene delivery using polymeric nano-carriers. J Control Release [Internet]. Elsevier B.V.; 2012;161:214–24. Available from: https://doi.org/10.1016/j.jconrel.2011.12.004
Nurbaeti SN, Brillault J, Tewes F, Olivier JC. Sustained-release microparticle dry powders of chloramphenicol palmitate or thiamphenicol palmitate prodrugs for lung delivery as aerosols. Eur J Pharm Sci. 2019;138:105028.
Rodrigues TC, Oliveira MLS, Soares-Schanoski A, Chavez-Rico SL, Figueiredo DB, Gonçalves VM, et al. Mucosal immunization with PspA (pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection. PLoS ONE. 2018;13:1–17.
Sarcinelli MA, Martins da Silva T, Artico Silva AD, Ferreira de Carvalho Patricio B, Mendes de Paiva FC, Santos de Lima R, et al. The pulmonary route as a way to drug repositioning in COVID-19 therapy. J Drug Deliv Sci Technol. 2021;63.
Newman SP. Delivering drugs to the lungs: the history of repurposing in the treatment of respiratory diseases. Adv. Drug Deliv. Rev. [Internet]. Elsevier B.V.; 2018;133:5–18. Available from: https://doi.org/10.1016/j.addr.2018.04.010
Mehta PP, Dhapte-Pawar VS. Repurposing drug molecules for new pulmonary therapeutic interventions. Drug Deliv. Transl. Res. 2020
Laplante M, Sabatini DM. MTOR signaling in growth control and disease. Cell. 2012;149:274–93.
doi: 10.1016/j.cell.2012.03.017
Mitani A, Ito K, Vuppusetty C, Barnes PJ, Mercado N. Restoration of corticosteroid sensitivity in chronic obstructive pulmonary disease by inhibition of mammalian target of rapamycin. Am J Respir Crit Care Med. 2016;193:143–53.
doi: 10.1164/rccm.201503-0593OC
He Y, Zuo C, Jia D, Bai P, Kong D, Chen D, et al. Loss of DP1 aggravates vascular remodeling in pulmonary arterial hypertension via mTORC1 signaling. Am J Respir Crit Care Med. 2020;201:1263–76.
doi: 10.1164/rccm.201911-2137OC
Mushaben EM, Brandt EB, Hershey GKK, Le Cras TD. Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma. PLoS One. 2013;8.
Omarjee L, Perrot F, Meilhac O, Mahe G, Bousquet G, Janin A. Immunometabolism at the cornerstone of inflammaging, immunosenescence, and autoimmunity in COVID-19. Aging (Albany. NY). 2020;12:1–16.
Husain A, Byrareddy SN. Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19. Chem. Biol. Interact. [Internet]. Elsevier B.V. 2020;331:109282. Available from: https://doi.org/10.1016/j.cbi.2020.109282
Haeri A, Osouli M, Bayat F, Alavi S, Dadashzadeh S. Nanomedicine approaches for sirolimus delivery: a review of pharmaceutical properties and preclinical studies. Artif Cells, Nanomedicine Biotechnol. 2018;46:1–14.
Carvalho SR, Watts AB, Peters JI, Liu S, Hengsawas S, Escotet-Espinoza MS, et al. Characterization and pharmacokinetic analysis of crystalline versus amorphous rapamycin dry powder via pulmonary administration in rats. Eur J Pharm Biopharm. 2014;88:136–47.
doi: 10.1016/j.ejpb.2014.05.008
Landh E, Moir LM, Gomes Dos Reis L, Traini D, Young PM, Ong HX. Inhaled rapamycin solid lipid nano particles for the treatment of Lymphangioleiomyomatosis. Eur J Pharm Sci. [Internet]. Elsevier. 2020;142:105098. Available from: https://doi.org/10.1016/j.ejps.2019.105098
Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm American Chemical Society. 2008;5:505–15.
doi: 10.1021/mp800051m
Pilcer G, Amighi K. Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm. 2010;392:1–19.
doi: 10.1016/j.ijpharm.2010.03.017
Huckaby JT, Lai SK. PEGylation for enhancing nanoparticle diffusion in mucus. Adv Drug Deliv Rev. [Internet]. Elsevier B.V. 2018;124:125–39. Available from: https://doi.org/10.1016/j.addr.2017.08.010
Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. [Internet]. Elsevier B.V. 2016;99:28–51. Available from: https://doi.org/10.1016/j.addr.2015.09.012
Lechanteur A, Evrard B. Influence of composition and spray-drying process parameters on carrier-free DPI properties and behaviors in the lung: a review. Pharmaceutics. 2020;12.
Elsayed MMA. Microstructural characterization of carrier-based dry powder inhalation excipients: insights and guidance. Int J Pharm. [Internet]. Elsevier. 2019;568:118482. Available from: https://doi.org/10.1016/j.ijpharm.2019.118482
Porsio B, Craparo EF, Mauro N, Giammona G, Cavallaro G. Mucus and cell-penetrating nanoparticles embedded in nano- into micro formulations for pulmonary delivery of ivacaftor in patients with cystic fibrosis. ACS Appl Mater Interfaces. 2018;10:165–81.
doi: 10.1021/acsami.7b14992
Craparo EF, Drago SE, Giammona G, Cavallaro G. Production of polymeric micro- and nanostructures with tunable properties as pharmaceutical delivery systems. Polymer (Guildf). 2020;200:122596.
Giammona G, Pitarresi G, Craparo EF, Cavallaro G, Buscemi S. New biodegradable hydrogels based on a photo-cross-linkable polyaspartamide and poly(ethylene glycol) derivatives. Release studies of an anticancer drug. Colloid Polym Sci. 2001;279:771–83.
Mendichi R, Giammona G, Cavallaro G, Giacometti SA. Molecular characterization of α, β-poly[(N-hydroxyethyl)-DL- aspartamide] by light scattering and viscometry studies. Polymer (Guildf). 2000;41:8649–57.
doi: 10.1016/S0032-3861(00)00185-3
Craparo EF, Cabibbo M, Conigliaro A, Barreca MM, Musumeci T, Giammona G, et al. Rapamycin-loaded polymeric nanoparticles as an advanced formulation for macrophage targeting in atherosclerosis. 2021
Craparo EF, Porsio B, Mauro N, Giammona G, Cavallaro G. Polyaspartamide-polylactide graft copolymers with tunable properties for the realization of fluorescent nanoparticles for imaging. Macromol Rapid Commun. 2015;36:1409–15.
doi: 10.1002/marc.201500154
Marques MRC, Loebenberg R, Almukainzi M. Simulated biologic fluids with possible application in dissolution testing. Dissolution Technol. 2011;15–28.
Pitarresi G, Palumbo FS, Calabrese R, Craparo EF, Giammona G. Crosslinked hyaluronan with a protein-like polymer: novel bioresorbable films for biomedical applications. J Biomed Mater Res - Part A. 2008;84:413–24.
Craparo EF, Licciardi M, Conigliaro A, Palumbo FS, Giammona G, Alessandro R, et al. Hepatocyte-targeted fluorescent nanoparticles based on a polyaspartamide for potential theranostic applications. Polymer (Guildf). Elsevier Ltd. 2015;70:257–70.
Campos MST, Fialho SL, Pereira BG, Yoshida MI, Oliveira MA. Kinetics studies of the degradation of sirolimus in solid state and in liquid medium. J Therm Anal Calorim. 2017;130:1653–61.
doi: 10.1007/s10973-017-6580-1
Zhao J, Weng G, Li J, Zhu J, Zhao J. Polyester-based nanoparticles for nucleic acid delivery. Mater Sci Eng C [Internet]. Elsevier. 2018;92:983–94. Available from: https://doi.org/10.1016/j.msec.2018.07.027
Linares-Alba MA, Gómez-Guajardo MB, Fonzar JF, Brooks DE, García-Sánchez GA, Bernad-Bernad MJ. Preformulation studies of a liposomal formulation containing sirolimus for the treatment of dry eye disease. J Ocul Pharmacol Ther. 2016;32:11–22.
doi: 10.1089/jop.2015.0032