Design of experiments approach on the preparation of dry inhaler chitosan composite formulations by supercritical CO2-assisted spray-drying

Cabral, Renato P.; Sousa, Ana M. L.; Silva, Ana Sofia; Paninho, Ana B.; Temtem, Márcio; Costa, Evaldo; Casimiro, Teresa; Aguiar‐Ricardo, Ana

doi:10.1016/j.supflu.2016.04.001

Cited by 23 publications

(39 citation statements)

References 44 publications

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“…The XRD diffractogram identifies the amorphous state of CHT_Fe@Au_POX-SH, similar to the XRD diffractogram reported for CHT alone [32]. No crystalline peaks were observed.…”

Section: Resultssupporting

confidence: 80%

“…However, nanoparticles are not in a suitable size for deep lung deposition, as they can be easily exhaled or muccociliary cleared out [29]. It has been established that the optimal aerodynamic diameter for particle deposition into the deep lung region is between 0.5 and 5 μm [30,31,32]. Therefore, to overcome this limitation, dry powder formulations containing both nanoparticles presented as nanocomposites and micro particles (nano-in-micro formulations) are the focus of study.…”

Section: Introductionmentioning

confidence: 99%

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Supercritical CO2-Assisted Spray Drying of Strawberry-Like Gold-Coated Magnetite Nanocomposites in Chitosan Powders for Inhalation

Silva

Fernández‐Lodeiro

et al. 2017

Materials

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Lung cancer is one of the leading causes of death worldwide. Therefore, it is of extreme importance to develop new systems that can deliver anticancer drugs into the site of action when initiating a treatment. Recently, the use of nanotechnology and particle engineering has enabled the development of new drug delivery platforms for pulmonary delivery. In this work, POXylated strawberry-like gold-coated magnetite nanocomposites and ibuprofen (IBP) were encapsulated into a chitosan matrix using Supercritical Assisted Spray Drying (SASD). The dry powder formulations showed adequate morphology and aerodynamic performances (fine particle fraction 48%–55% and aerodynamic diameter of 2.6–2.8 µm) for deep lung deposition through the pulmonary route. Moreover, the release kinetics of IBP was also investigated showing a faster release of the drug at pH 6.8, the pH of lung cancer. POXylated strawberry-like gold-coated magnetite nanocomposites proved to have suitable sizes for cellular internalization and their fluorescent capabilities enable their future use in in vitro cell based assays. As a proof-of-concept, the reported results show that these nano-in-micro formulations could be potential drug vehicles for pulmonary administration.

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“…The XRD diffractogram identifies the amorphous state of CHT_Fe@Au_POX-SH, similar to the XRD diffractogram reported for CHT alone [32]. No crystalline peaks were observed.…”

Section: Resultssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Supercritical CO2-Assisted Spray Drying of Strawberry-Like Gold-Coated Magnetite Nanocomposites in Chitosan Powders for Inhalation

Silva

Fernández‐Lodeiro

et al. 2017

Materials

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“…Carbon dioxide UN1013 was obtained from Air Liquid. The POxylated polyurea dendrimers (PURE G4 OMeOx 48 and PURE G4 OEtOx 48 ) were synthesized as reported . FTIR spectra were obtained with a PerkinElmer Spectrum 1000 instrument.…”

Section: Methodsmentioning

confidence: 99%

POxylated Dendrimer‐Based Nano‐in‐Micro Dry Powder Formulations for Inhalation Chemotherapy

et al. 2018

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POxylated polyurea dendrimer (PUREG4OOx48)‐based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO2‐assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. In vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREG4OOx48 nanoparticles were much more cytotoxic than the free drug. Additionally, the DPFs did not show higher cytotoxicity than the respective nanoparticles, and DOX‐DPFs showed a higher chemotherapeutic effect than PTX formulations in adenocarcinoma cells.

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“…SASD Process and Apparatus : 2.5 g of CHT were dissolved in acidic water (acetic acid 1% v/v) under stirring for 24 h. The solution was filtered and 360 mg of PURE G4 OEtOx or PURE G4 OMeOx previously dissolved in 14.5 mL of ethanol was added. The mixture was homogenized under stirring and fed to a laboratory scale SASD apparatus . After liquefying in a cryogenic bath, liquid carbon dioxide was pumped through a high‐pressure pump (HPLC pump K‐501, Knauer) into a heated bath and then mixed and solubilized within the liquid solution in the static mixer at 10 MPa.…”

Section: Methodsmentioning

confidence: 99%

Nano-in-Micro POxylated Polyurea Dendrimers and Chitosan Dry Powder Formulations for Pulmonary Delivery

Restani

Silva

Pires

et al. 2016

Part. Part. Syst. Charact.

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Pulmonary administration offers excellent advantages over conventional drug delivery routes, including increasing therapeutics bioavailability, and avoiding long‐term safety issues. Formulations of nano‐in‐micro dry powders for lung delivery are engineered using (S)‐ibuprofen as a model drug. These biodegradable formulations comprise nanoparticles of drug‐loaded POxylated polyurea dendrimers coated with chitosan using supercritical‐fluid‐assisted spray drying. The formulations are characterized in terms of morphology, particle‐size distribution, in vitro aerodynamic particle pulmonary distribution, and glutathione‐S‐transferase assay. It is demonstrated that ibuprofen‐loaded nanoparticles can be successfully incorporated into microspheres with adequate aerodynamic properties, mass median aerodynamic diameter (1.86–3.83 μm), and fine particle fraction (28%–45%), for deposition into the deep lung. The (S)‐ibuprofen dry powder formulations show enhanced solubility, high swelling behavior and a sustained drug release at physiologic pH. Also, POxylated polyureas decrease the (S)‐ibuprofen toxic effect on cancer cellular growth. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assays show no significant cytotoxicity on the metabolic activity of human lung adenocarcinoma ephithelial (A549) cell line for the lowest concentration (1 × 10−3 m), even for longer periods of contact with the cells (up to 120 h), and in the normal human dermal fibroblasts cell line the toxic effect is also reduced.

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Design of experiments approach on the preparation of dry inhaler chitosan composite formulations by supercritical CO2-assisted spray-drying

Cited by 23 publications

References 44 publications

Supercritical CO2-Assisted Spray Drying of Strawberry-Like Gold-Coated Magnetite Nanocomposites in Chitosan Powders for Inhalation

Supercritical CO2-Assisted Spray Drying of Strawberry-Like Gold-Coated Magnetite Nanocomposites in Chitosan Powders for Inhalation

POxylated Dendrimer‐Based Nano‐in‐Micro Dry Powder Formulations for Inhalation Chemotherapy

Nano-in-Micro POxylated Polyurea Dendrimers and Chitosan Dry Powder Formulations for Pulmonary Delivery

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