Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation

Elshaimaa Sayed, Christina Karavasili, Ketan Ruparelia, Rita Haj-Ahmad, Georgia Charalambopoulou, Theodore Steriotis, Dimitra Giasafaki, Paul Cox, Neenu Singh, Lefki Pavlina N. Giassafaki, Aggeliki Mpenekou, Catherine K. Markopoulou, Ioannis S. Vizirianakis, Ming Wei Chang, Dimitrios G. Fatouros, Zeeshan Ahmad

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Encapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials.

LanguageEnglish
Pages142-155
Number of pages14
JournalJournal of Controlled Release
Volume278
Early online date30 Mar 2018
DOIs
Publication statusPublished - 28 May 2018

Fingerprint

Antineoplastic Agents
Solubility
Water
Silicon Dioxide
Pharmaceutical Preparations
Permeability
Chalcone
Caco-2 Cells
Microwaves
Particle Size
Biological Availability
Intestines
In Vitro Techniques
Technology
Drug Liberation

Keywords

  • Chalcones
  • Cytocompatibility
  • Electrohydrodynamic atomization
  • Electrospraying
  • Ex vivo
  • Mesoporous silica
  • Molecular modeling
  • Poor solubility

Cite this

Sayed, Elshaimaa ; Karavasili, Christina ; Ruparelia, Ketan ; Haj-Ahmad, Rita ; Charalambopoulou, Georgia ; Steriotis, Theodore ; Giasafaki, Dimitra ; Cox, Paul ; Singh, Neenu ; Giassafaki, Lefki Pavlina N. ; Mpenekou, Aggeliki ; Markopoulou, Catherine K. ; Vizirianakis, Ioannis S. ; Chang, Ming Wei ; Fatouros, Dimitrios G. ; Ahmad, Zeeshan. / Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent : in vitro and ex vivo evaluation. In: Journal of Controlled Release. 2018 ; Vol. 278. pp. 142-155.
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Sayed, E, Karavasili, C, Ruparelia, K, Haj-Ahmad, R, Charalambopoulou, G, Steriotis, T, Giasafaki, D, Cox, P, Singh, N, Giassafaki, LPN, Mpenekou, A, Markopoulou, CK, Vizirianakis, IS, Chang, MW, Fatouros, DG & Ahmad, Z 2018, 'Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation', Journal of Controlled Release, vol. 278, pp. 142-155. https://doi.org/10.1016/j.jconrel.2018.03.031

Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent : in vitro and ex vivo evaluation. / Sayed, Elshaimaa; Karavasili, Christina; Ruparelia, Ketan; Haj-Ahmad, Rita; Charalambopoulou, Georgia; Steriotis, Theodore; Giasafaki, Dimitra; Cox, Paul; Singh, Neenu; Giassafaki, Lefki Pavlina N.; Mpenekou, Aggeliki; Markopoulou, Catherine K.; Vizirianakis, Ioannis S.; Chang, Ming Wei; Fatouros, Dimitrios G.; Ahmad, Zeeshan.

In: Journal of Controlled Release, Vol. 278, 28.05.2018, p. 142-155.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent

T2 - Journal of Controlled Release

AU - Sayed, Elshaimaa

AU - Karavasili, Christina

AU - Ruparelia, Ketan

AU - Haj-Ahmad, Rita

AU - Charalambopoulou, Georgia

AU - Steriotis, Theodore

AU - Giasafaki, Dimitra

AU - Cox, Paul

AU - Singh, Neenu

AU - Giassafaki, Lefki Pavlina N.

AU - Mpenekou, Aggeliki

AU - Markopoulou, Catherine K.

AU - Vizirianakis, Ioannis S.

AU - Chang, Ming Wei

AU - Fatouros, Dimitrios G.

AU - Ahmad, Zeeshan

N1 - No accepted version. Not for REF. New member of staff.

PY - 2018/5/28

Y1 - 2018/5/28

N2 - Encapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials.

AB - Encapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials.

KW - Chalcones

KW - Cytocompatibility

KW - Electrohydrodynamic atomization

KW - Electrospraying

KW - Ex vivo

KW - Mesoporous silica

KW - Molecular modeling

KW - Poor solubility

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DO - 10.1016/j.jconrel.2018.03.031

M3 - Article

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EP - 155

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