Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant
Abstract
:1. Introduction
2. Results
2.1. Scanning Electron Microscopy (SEM)
2.2. Loading and Encapsulation Efficiency
2.3. Powder X-ray Diffractometry (pXRD)
2.4. Differential Scanning Calorimetry (DSC)
2.5. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR)
2.6. Pore Analysis
2.7. In Vitro Release Studies
2.8. In Vitro Cell Studies
Cytocompatibility of MSN Particles and Cellular Morphology (Caco-2 Cell Culture)
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Aprepitant Loading into MSNs
4.3. HPLC Analysis of Aprepitant
4.4. Quantification of Drug Loading
4.5. Scanning Electron Microscopy (SEM)
4.6. Powder X-ray Diffracrometry (pXRD)
4.7. Differential Scanning Calorimetry (DSC)
4.8. Thermogravimetric Analysis (TGA)
4.9. ATR-FTIR Spectroscopy
4.10. Determination of Pore Properties
4.11. In Vitro Release Studies
4.12. Cytotoxicity Studies
4.12.1. Caco-2 Cell Cultures
4.12.2. Cytotoxicity Assessment
4.13. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Chircov, C.; Spoială, A.; Păun, C.; Crăciun, L.; Ficai, D.; Ficai, A.; Andronescu, E.; Turculeƫ, Ș.C. Mesoporous Silica Platforms with Potential Applications in Release and Adsorption of Active Agents. Molecules 2020, 25, 3814. [Google Scholar] [CrossRef] [PubMed]
- Manzano, M.; Vallet-Regí, M. Mesoporous Silica Nanoparticles for Drug Delivery. Adv. Funct. Mater. 2020, 30, 1902634. [Google Scholar] [CrossRef]
- McCarthy, C.A.; Ahern, R.J.; Devine, K.J.; Crean, A.M. Role of Drug Adsorption onto the Silica Surface in Drug Release from Mesoporous Silica Systems. Mol. Pharm. 2018, 15, 141–149. [Google Scholar] [CrossRef] [PubMed]
- Maleki, A.; Kettiger, H.; Schoubben, A.; Rosenholm, J.M.; Ambrogi, V.; Hamidi, M. Mesoporous Silica Materials: From Physico-Chemical Properties to Enhanced Dissolution of Poorly Water-Soluble Drugs. J. Control. Release 2017, 262, 329–347. [Google Scholar] [CrossRef]
- Martín, A.; Morales, V.; Ortiz-Bustos, J.; Pérez-Garnes, M.; Bautista, L.F.; García-Muñoz, R.A.; Sanz, R. Modelling the Adsorption and Controlled Release of Drugs from the Pure and Amino Surface-Functionalized Mesoporous Silica Hosts. Microporous Mesoporous Mater. 2018, 262, 23–34. [Google Scholar] [CrossRef]
- Gisbert-Garzarán, M.; Vallet-Regí, M. Influence of the Surface Functionalization on the Fate and Performance of Mesoporous Silica Nanoparticles. Nanomaterials 2020, 10, 916. [Google Scholar] [CrossRef] [PubMed]
- Olver, I.; Shelukar, S.; Thompson, K.C. Nanomedicines in the Treatment of Emesis during Chemotherapy: Focus on Aprepitant. Int. J. Nanomed. 2007, 2, 13–18. [Google Scholar] [CrossRef]
- Sharma, R.; Kamboj, S.; Singh, G.; Rana, V. Development of Aprepitant Loaded Orally Disintegrating Films for Enhanced Pharmacokinetic Performance. Eur. J. Pharm. Sci. 2016, 84, 55–69. [Google Scholar] [CrossRef]
- Kesisoglou, F.; Wu, Y. Understanding the Effect of API Properties on Bioavailability through Absorption Modeling. AAPS J. 2008, 10, 516–525. [Google Scholar] [CrossRef]
- Kesisoglou, F.; Mitra, A. Crystalline Nanosuspensions as Potential Toxicology and Clinical Oral Formulations for BCS II/IV Compounds. AAPS J. 2012, 14, 677–687. [Google Scholar] [CrossRef] [Green Version]
- Kesisoglou, F.; Panmai, S.; Wu, Y. Nanosizing—Oral Formulation Development and Biopharmaceutical Evaluation. Adv. Drug Deliv. Rev. 2007, 59, 631–644. [Google Scholar] [CrossRef]
- Shono, Y.; Jantratid, E.; Kesisoglou, F.; Reppas, C.; Dressman, J.B. Forecasting in Vivo Oral Absorption and Food Effect of Micronized and Nanosized Aprepitant Formulations in Humans. Eur. J. Pharm. Biopharm. 2010, 76, 95–104. [Google Scholar] [CrossRef]
- Ren, L.; Zhou, Y.; Wei, P.; Li, M.; Chen, G. Preparation and Pharmacokinetic Study of Aprepitant–Sulfobutyl Ether-β-Cyclodextrin Complex. AAPS PharmSciTech 2014, 15, 121–130. [Google Scholar] [CrossRef] [Green Version]
- Kamboj, S.; Rana, V. Formulation Optimization of Aprepitant Microemulsion-Loaded Silicated Corn Fiber Gum Particles for Enhanced Bioavailability. Drug Dev. Ind. Pharm. 2016, 42, 1267–1282. [Google Scholar] [CrossRef] [PubMed]
- Kamboj, S.; Sharma, R.; Singh, K.; Rana, V. Aprepitant Loaded Solid Preconcentrated Microemulsion for Enhanced Bioavailability: A Comparison with Micronized Aprepitant. Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 2015, 78, 90–102. [Google Scholar] [CrossRef] [PubMed]
- Niederquell, A.; Kuentz, M. Proposal of Stability Categories for Nano-Dispersions Obtained from Pharmaceutical Self-Emulsifying Formulations. Int. J. Pharm. 2013, 446, 70–80. [Google Scholar] [CrossRef]
- Liu, J.; Zou, M.; Piao, H.; Liu, Y.; Tang, B.; Gao, Y.; Ma, N.; Cheng, G. Characterization and Pharmacokinetic Study of Aprepitant Solid Dispersions with Soluplus. Molecules 2015, 20, 11345–11356. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Penumetcha, S.S.; Gutta, L.N.; Dhanala, H.; Yamili, S.; Challa, S.; Rudraraju, S.; Rudraraju, S.; Rudraraju, V. Hot Melt Extruded Aprepitant–Soluplus Solid Dispersion: Preformulation Considerations, Stability and in Vitro Study. Drug Dev. Ind. Pharm. 2016, 42, 1609–1620. [Google Scholar] [CrossRef] [PubMed]
- Yeo, S.; An, J.; Park, C.; Kim, D.; Lee, J. Design and Characterization of Phosphatidylcholine-Based Solid Dispersions of Aprepitant for Enhanced Solubility and Dissolution. Pharmaceutics 2020, 12, 407. [Google Scholar] [CrossRef] [PubMed]
- Punčochová, K.; Vukosavljevic, B.; Hanuš, J.; Beránek, J.; Windbergs, M.; Štěpánek, F. Non-Invasive Insight into the Release Mechanisms of a Poorly Soluble Drug from Amorphous Solid Dispersions by Confocal Raman Microscopy. Eur. J. Pharm. Biopharm. Off. J. Arb. Pharm. Verfahr. EV 2016, 101, 119–125. [Google Scholar] [CrossRef] [PubMed]
- Punčochová, K.; Ewing, A.V.; Gajdošová, M.; Pekárek, T.; Beránek, J.; Kazarian, S.G.; Štěpánek, F. The Combined Use of Imaging Approaches to Assess Drug Release from Multicomponent Solid Dispersions. Pharm. Res. 2017, 34, 990–1001. [Google Scholar] [CrossRef] [Green Version]
- Barmpalexis, P.; Grypioti, A.; Eleftheriadis, G.K.; Fatouros, D.G. Development of a New Aprepitant Liquisolid Formulation with the Aid of Artificial Neural Networks and Genetic Programming. AAPS PharmSciTech 2018, 19, 741–752. [Google Scholar] [CrossRef]
- Ridhurkar, D.N.; Ansari, K.A.; Kumar, D.; Kaul, N.S.; Krishnamurthy, T.; Dhawan, S.; Pillai, R. Inclusion Complex of Aprepitant with Cyclodextrin: Evaluation of Physico-Chemical and Pharmacokinetic Properties. Drug Dev. Ind. Pharm. 2013, 39, 1783–1792. [Google Scholar] [CrossRef]
- Sayed, E.; Karavasili, C.; Ruparelia, K.; Haj-Ahmad, R.; Charalambopoulou, G.; Steriotis, T.; Giasafaki, D.; Cox, P.; Singh, N.; Giassafaki, L.-P.N.; et al. Electrosprayed Mesoporous Particles for Improved Aqueous Solubility of a Poorly Water Soluble Anticancer Agent: In Vitro and Ex Vivo Evaluation. J. Control. Release 2018, 278, 142–155. [Google Scholar] [CrossRef]
- Bremmell, K.E.; Prestidge, C.A. Enhancing Oral Bioavailability of Poorly Soluble Drugs with Mesoporous Silica Based Systems: Opportunities and Challenges. Drug Dev. Ind. Pharm. 2019, 45, 349–358. [Google Scholar] [CrossRef]
- Wang, Y.; Sun, L.; Jiang, T.; Zhang, J.; Zhang, C.; Sun, C.; Deng, Y.; Sun, J.; Wang, S. The Investigation of MCM-48-Type and MCM-41-Type Mesoporous Silica as Oral Solid Dispersion Carriers for Water Insoluble Cilostazol. Drug Dev. Ind. Pharm. 2014, 40, 819–828. [Google Scholar] [CrossRef] [PubMed]
- Kruk, M.; Jaroniec, M.; Sayari, A. Relations between Pore Structure Parameters and Their Implications for Characterization of MCM-41 Using Gas Adsorption and X-Ray Diffraction. Chem. Mater. 1999, 11, 492–500. [Google Scholar] [CrossRef]
- Sayari, A. Novel Synthesis of High-Quality MCM-48 Silica. J. Am. Chem. Soc. 2000, 122, 6504–6505. [Google Scholar] [CrossRef]
- Datt, A.; El-Maazawi, I.; Larsen, S.C. Aspirin Loading and Release from MCM-41 Functionalized with Aminopropyl Groups via Co-Condensation or Postsynthesis Modification Methods. J. Phys. Chem. C 2012, 116, 18358–18366. [Google Scholar] [CrossRef]
- Umamaheswari, V. Isopropylation of M-Cresol over Mesoporous Al–MCM-41 Molecular Sieves. J. Catal. 2002, 210, 367–374. [Google Scholar] [CrossRef]
- Helmy, R.; Zhou, G.X.; Chen, Y.W.; Crocker, L.; Wang, T.; Wenslow, R.M.; Vailaya, A. Characterization and Quantitation of Aprepitant Drug Substance Polymorphs by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy. Anal. Chem. 2003, 75, 605–611. [Google Scholar] [CrossRef] [PubMed]
- Pirzada, T.; Arvidson, S.A.; Saquing, C.D.; Shah, S.S.; Khan, S.A. Hybrid Silica–PVA Nanofibers via Sol–Gel Electrospinning. Langmuir 2012, 28, 5834–5844. [Google Scholar] [CrossRef]
- Innocenzi, P.; Falcaro, P.; Grosso, D.; Babonneau, F. Order−Disorder Transitions and Evolution of Silica Structure in Self-Assembled Mesostructured Silica Films Studied through FTIR Spectroscopy. J. Phys. Chem. B 2003, 107, 4711–4717. [Google Scholar] [CrossRef]
- Eleftheriadis, G.K.; Filippousi, M.; Tsachouridou, V.; Darda, M.-A.; Sygellou, L.; Kontopoulou, I.; Bouropoulos, N.; Steriotis, T.; Charalambopoulou, G.; Vizirianakis, I.S.; et al. Evaluation of Mesoporous Carbon Aerogels as Carriers of the Non-Steroidal Anti-Inflammatory Drug Ibuprofen. Int. J. Pharm. 2016, 515, 262–270. [Google Scholar] [CrossRef] [PubMed]
- Andriotis, E.G.; Eleftheriadis, G.K.; Karavasili, C.; Fatouros, D.G. Development of Bio-Active Patches Based on Pectin for the Treatment of Ulcers and Wounds Using 3D-Bioprinting Technology. Pharmaceutics 2020, 12, 56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heikkilä, T.; Santos, H.A.; Kumar, N.; Murzin, D.Y.; Salonen, J.; Laaksonen, T.; Peltonen, L.; Hirvonen, J.; Lehto, V.-P. Cytotoxicity Study of Ordered Mesoporous Silica MCM-41 and SBA-15 Microparticles on Caco-2 Cells. Eur. J. Pharm. Biopharm. 2010, 74, 483–494. [Google Scholar] [CrossRef]
- Zheng, N.; Li, J.; Xu, C.; Xu, L.; Li, S.; Xu, L. Mesoporous Silica Nanorods for Improved Oral Drug Absorption. Artif. Cells Nanomedicine Biotechnol. 2018, 46, 1132–1140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Joyce, P.; Ulmefors, H.; Maghrebi, S.; Subramaniam, S.; Wignall, A.; Jõemetsa, S.; Höök, F.; Prestidge, C.A. Enhancing the Cellular Uptake and Antibacterial Activity of Rifampicin through Encapsulation in Mesoporous Silica Nanoparticles. Nanomaterials 2020, 10, 815. [Google Scholar] [CrossRef] [Green Version]
- Lang, Y.; Finn, D.P.; Pandit, A.; Walsh, P.J. Pharmacological Activity of Ibuprofen Released from Mesoporous Silica. J. Mater. Sci. Mater. Med. 2012, 23, 73–80. [Google Scholar] [CrossRef] [PubMed]
- Zaharudin, N.S.; Mohamed Isa, E.D.; Ahmad, H.; Abdul Rahman, M.B.; Jumbri, K. Functionalized Mesoporous Silica Nanoparticles Templated by Pyridinium Ionic Liquid for Hydrophilic and Hydrophobic Drug Release Application. J. Saudi Chem. Soc. 2020, 24, 289–302. [Google Scholar] [CrossRef]
- Cai, Q.; Luo, Z.-S.; Pang, W.-Q.; Fan, Y.-W.; Chen, X.-H.; Cui, F.-Z. Dilute Solution Routes to Various Controllable Morphologies of MCM-41 Silica with a Basic Medium. Chem. Mater. 2001, 13, 258–263. [Google Scholar] [CrossRef]
- Stöber, W.; Fink, A.; Bohn, E. Controlled Growth of Monodisperse Silica Spheres in the Micron Size Range. J. Colloid Interface Sci. 1968, 26, 62–69. [Google Scholar] [CrossRef]
- Gisbert-Garzarán, M.; Berkmann, J.C.; Giasafaki, D.; Lozano, D.; Spyrou, K.; Manzano, M.; Steriotis, T.; Duda, G.N.; Schmidt-Bleek, K.; Charalambopoulou, G.; et al. Engineered pH-Responsive Mesoporous Carbon Nanoparticles for Drug Delivery. ACS Appl. Mater. Interfaces 2020, 12, 14946–14957. [Google Scholar] [CrossRef]
- Vallet-Regi, M.; Rámila, A.; del Real, R.P.; Pérez-Pariente, J. A New Property of MCM-41: Drug Delivery System. Chem. Mater. 2001, 13, 308–311. [Google Scholar] [CrossRef]
- Zhang, Y.; Huo, M.; Zhou, J.; Zou, A.; Li, W.; Yao, C.; Xie, S. DDSolver: An Add-In Program for Modeling and Comparison of Drug Dissolution Profiles. AAPS J. 2010, 12, 263–271. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mosmann, T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. J. Immunol. Methods 1983, 65, 55–63. [Google Scholar] [CrossRef]
- Spanakis, M.; Bouropoulos, N.; Theodoropoulos, D.; Sygellou, L.; Ewart, S.; Moschovi, A.M.; Siokou, A.; Niopas, I.; Kachrimanis, K.; Nikolakis, V.; et al. Controlled Release of 5-Fluorouracil from Microporous Zeolites. Nanomedicine Nanotechnol. Biol. Med. 2014, 10, 197–205. [Google Scholar] [CrossRef] [Green Version]
- Karavasili, C.; Amanatiadou, E.P.; Sygellou, L.; Giasafaki, D.K.; Steriotis, T.A.; Charalambopoulou, G.C.; Vizirianakis, I.S.; Fatouros, D.G. Development of New Drug Delivery System Based on Ordered Mesoporous Carbons: Characterisation and Cytocompatibility Studies. J. Mater. Chem. B 2013, 1, 3167. [Google Scholar] [CrossRef] [PubMed]
Particle Type | Encapsulation Efficiency (%) | Drug Loading (%) |
---|---|---|
MCM-41 | 12.66 | 5.97 |
MCM-48 | 29.67 | 12.92 |
Particle Type | Drug Loading (%) |
---|---|
MCM-41 | 4.52 |
MCM-48 | 13.06 |
Sample | BET Area (m2/g) | Pore Volume 1 (cm3/g) | Pore Diameter 2 (nm) |
---|---|---|---|
MCM-41 | 1145 | 0.98 | 3.8 |
Apr-MCM-41 | 905 | 0.80 | 3.8 |
MCM-48 | 1165 | 0.96 | 3.4 |
Apr-MCM-48 | 690 | 0.51 | 3.4 |
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Christoforidou, T.; Giasafaki, D.; Andriotis, E.G.; Bouropoulos, N.; Theodoroula, N.F.; Vizirianakis, I.S.; Steriotis, T.; Charalambopoulou, G.; Fatouros, D.G. Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant. Int. J. Mol. Sci. 2021, 22, 1896. https://doi.org/10.3390/ijms22041896
Christoforidou T, Giasafaki D, Andriotis EG, Bouropoulos N, Theodoroula NF, Vizirianakis IS, Steriotis T, Charalambopoulou G, Fatouros DG. Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant. International Journal of Molecular Sciences. 2021; 22(4):1896. https://doi.org/10.3390/ijms22041896
Chicago/Turabian StyleChristoforidou, Theodora, Dimitra Giasafaki, Eleftherios G. Andriotis, Nikolaos Bouropoulos, Nikoleta F. Theodoroula, Ioannis S. Vizirianakis, Theodore Steriotis, Georgia Charalambopoulou, and Dimitrios G. Fatouros. 2021. "Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant" International Journal of Molecular Sciences 22, no. 4: 1896. https://doi.org/10.3390/ijms22041896