Inhalable Microparticles Embedding Calcium Phosphate Nanoparticles for Heart Targeting: The Formulation Experimental Design.

Eride Quarta,Dimitrios M Rekkas,Alessandro Dotti,Francesca Buttini,Giovanna Trevisi,Daniele Catalucci,Lorenzo Degli Esposti,Alessandra Rossi,Paolo Colombo,Fabio Sonvico,Gaia Colombo,Claudio De Luca,Tin Wui Wong,Ruggero Bettini,Michele Iafisco

doi:10.3390/pharmaceutics13111825

Abstract

Inhalation of Calcium Phosphate nanoparticles (CaPs) has recently unmasked the potential of this nanomedicine for a respiratory lung-to-heart drug delivery targeting the myocardial cells. In this work, we investigated the development of a novel highly respirable dry powder embedding crystalline CaPs. Mannitol was selected as water soluble matrix excipient for constructing respirable dry microparticles by spray drying technique. A Quality by Design approach was applied for understanding the effect of the feed composition and spraying feed rate on typical quality attributes of inhalation powders. The in vitro aerodynamic behaviour of powders was evaluated using a medium resistance device. The inner structure and morphology of generated microparticles were also studied. The 1:4 ratio of CaPs/mannitol led to the generation of hollow microparticles, with the best aerodynamic performance. After microparticle dissolution, the released nanoparticles kept their original size.

Highlights

In a follow-up paper, the in vivo administration by nebulization of MP-loaded Calcium Phosphate nanoparticles (CaPs) enabled their internalization into cardiomyocytes and restored cardiac function in a mouse model of cardiomyopathy [2]
In consideration of its relevance for the industrial manufacturing time, the feed rate of the liquid to dry was selected as a process parameter
We have studied the preparation by spray drying of inhalable mannitol microparticles embedding nanoparticles of calcium phosphate

Summary

Introduction

In a follow-up paper, the in vivo administration by nebulization of MP-loaded CaPs enabled their internalization into cardiomyocytes and restored cardiac function in a mouse model of cardiomyopathy [2]. This heart targeted treatment took advantage of the pulmonary administration route for cardiac accumulation of drug loaded CaPs. drug loaded CaPs (hydrodynamic mean diameter < 200 nm) present complexity for the administration by inhalation due to difficulty to control their nano size before and after delivery. Their physical stability is improved, the dose control is more predictable, and the product could be used in home or care settings

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Results

Conclusion