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

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1825
Author(s):  
Eride Quarta ◽  
Fabio Sonvico ◽  
Ruggero Bettini ◽  
Claudio De Luca ◽  
Alessandro Dotti ◽  
...  

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.

2014 ◽  
Vol 70 (a1) ◽  
pp. C67-C67
Author(s):  
Babak Mostaghaci ◽  
Brigitta Loretz ◽  
Robert Haberkorn ◽  
Guido Kickelbick ◽  
Claus-Michael Lehr

Calcium phosphate has been the point of interest for in vitro gene delivery for many years because of its biocompatibility and straight forward application. However, there are some limitations regarding in vivo administration of these particles mostly because of vast agglomeration of the particles and lack of strong bond between the particles and pDNA. We introduced a simple single step method to functionalize calcium phosphate nanoparticles with Aminosilanes having a different number of amine groups. The nanoparticles were characterized chemically and structurally and their toxicity and interaction with pDNA were studied as well. Results revealed that different crystalline phase of calcium phosphate nanoparticles (Brushite and Hydroxyapatite) with a size below 150 nm were prepared, depending on conditions of synthesis and phase, each with a narrow size distribution. The aminosilane agents caused oriented nucleation and growth of crystallites and can decrease the pH for producing hydroxyapatite phase. The phenomenon could be revealed with the presence of anisotropy in the structure of synthesized hydroxyapatite. The number of amine groups in the Aminosilane agent could change the phase transition pH. Brushite particles revealed to have stronger interaction with pDNA mostly because of their higher positive surface charge. Both particles showed blood compatibility and negligible toxicity. Transfection experiment revealed the capability of both brushite and hydroxyapatite particles to transfect A549 and HEK293 cells. The new modified nanoparticles can be stored in a dried state and re-dispersed easily at the time of administration. Moreover, the transfection efficiency is higher in comparison with conventional calcium phosphate. This study showed the impact of presence and type of the modifying agent on the crystal structure and the amount of surface functionalization of nanoparticles, which in consequence influenced their interaction with cells.


2020 ◽  
Vol 110 ◽  
pp. 254-265
Author(s):  
Leonardo Rojas-Sánchez ◽  
Ejuan Zhang ◽  
Viktoriya Sokolova ◽  
Maohua Zhong ◽  
Hu Yan ◽  
...  

2017 ◽  
Vol 64 ◽  
pp. 401-410 ◽  
Author(s):  
Viktoriya Sokolova ◽  
Zou Shi ◽  
Shunmei Huang ◽  
Yanqin Du ◽  
Mathis Kopp ◽  
...  

2017 ◽  
Vol 29 (04) ◽  
pp. 1750027 ◽  
Author(s):  
Ko-Chung Yen ◽  
I-Hua Chen ◽  
Feng-Huei Lin

A major aim of gene therapy is the efficient and specific delivery of therapeutic gene into the desired target tissues. Development of reliable vectors is a major challenge in gene therapy. The aim of this study is to develop calcium phosphate nanoparticles as novel non-viral vectors for the gene delivery system. Calcium phosphate nanoparticles were prepared by water-in-oil microemulsion method with a water to surfactant molar ratio, Wo [Formula: see text] 2–10. This paper studies the design and synthesis of ultra-low size, highly monodispersed DNA doped calcium phosphate nanoparticles of size around 100[Formula: see text]nm in diameter. The structure of DNA-calcium phosphate nanocomplex observed by TEM was displayed as a shell-like structure. This study used pEGFP as a reporter gene. The encapsulating efficiency to encapsulate DNA inside the nanoparticles was greater than 80%. In the MTT test, both calcium phosphate nanoparticles and DNA-calcium phosphate nanocomplex have no negative effect for 293T cells. By gel electrophoresis of free and entrapped pEGFP DNA, the DNA encapsulated inside the nanoparticles was protected from the external DNaseI environment. In vitro transfection studies in 293T cell-line, the DNA-calcium phosphate nanocomplex could be used safely to transfer the encapsulated DNA into the 293T cells and expression green fluorescent protein. The characteristic of DNA-calcium phosphate nanocomplex to deliver DNA belongs to slow release. The property of DNA-calcium phosphate nanocomplex was fit in the requirement of non-viral vectors for the gene delivery system.


2020 ◽  
Vol 36 (10) ◽  
pp. 1343-1355 ◽  
Author(s):  
Wen Zhou ◽  
Xian Peng ◽  
Xuedong Zhou ◽  
Michael D. Weir ◽  
Mary Anne S. Melo ◽  
...  

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