Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Analysis of Gefitinib and Azacitidine in Formulations
2.3. Preparation of NLC Formulations
2.4. Physicochemical Characterization
2.4.1. Particle Size, Polydispersity Index, and Zeta Potential Measurements
2.4.2. Calculation of Drug Content and Entrapment Efficiency
2.5. Differential Scanning Calorimetry (DSC)
2.6. Powder X-ray Diffractometer (PXRD)
2.7. In Vitro Release Study
2.8. In Vitro Cytotoxicity Study
2.9. Hemocompatibility Study
2.10. Statistical Analysis
3. Results and Discussion
3.1. Method Performance and Assay Validation
3.2. Physicochemical Properties of Prepared NLCs
3.3. DSC
3.4. PXRD
3.5. In Vitro Release Study
3.6. In Vitro Cytotoxicity against Lung Cancer Cell Line
3.6.1. Effect of Anticancer Agents’ Codelivery
3.6.2. Effect of NLC Formulations
3.7. Hemocompatibility Study
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Deng, Y.; Zhao, P.; Zhou, L.; Xiang, D.; Hu, J.; Liu, Y.; Ruan, J.; Ye, X.; Zheng, Y.; Yao, J.; et al. Epidemiological trends of tracheal, bronchus, and lung cancer at the global, regional, and national levels: A population-based study. J. Hematol. Oncol. 2020, 13, 98. [Google Scholar] [CrossRef]
- Shanker, M.; Willcutts, D.; Roth, J.A.; Ramesh, R. Drug resistance in lung cancer. Lung Cancer Targets Ther. 2010, 1, 23–36. [Google Scholar]
- Huang, J.; Deng, G.; Wang, S.; Zhao, T.; Chen, Q.; Yang, Y.; Yang, Y.; Zhang, J.; Nan, Y.; Liu, Z.; et al. A NIR-II Photoactivatable “ROS Bomb” with High-Density Cu2O-Supported MoS2 Nanoflowers for Anticancer Therapy. Adv. Sci. 2023, 2302208. [Google Scholar]
- Yang, Y.; Huang, J.; Liu, M.; Qiu, Y.; Chen, Q.; Zhao, T.; Xiao, Z.; Yang, Y.; Jiang, Y.; Huang, Q.; et al. Emerging Sonodynamic Therapy-Based Nanomedicines for Cancer Immunotherapy. Adv. Sci. 2023, 10, 2204365. [Google Scholar]
- Gong, J.; Shi, T.; Liu, J.; Pei, Z.; Liu, J.; Ren, X.; Li, F.; Qiu, F. Dual-drug codelivery nanosystems: An emerging approach for overcoming cancer multidrug resistance. Biomed. Pharmacother. 2023, 161, 114505. [Google Scholar]
- Hu, Y.; Zhang, J.; Hu, H.; Xu, S.; Xu, L.; Chen, E. Gefitinib encapsulation based on nano-liposomes for enhancing the curative effect of lung cancer. Cell Cycle 2020, 19, 3581–3594. [Google Scholar] [CrossRef]
- Javadi, S.; Zhiani, M.; Mousavi, M.A.; Fathi, M. Crosstalk between Epidermal Growth Factor Receptors (EGFR) and integrins in resistance to EGFR tyrosine kinase inhibitors (TKIs) in solid tumors. Eur. J. Cell Biol. 2020, 99, 151083. [Google Scholar]
- Sherif, A.Y.; Harisa, G.I.; Alanazi, F.K. The Chimera of TPGS and Nanoscale Lipid Carriers as Lymphatic Drug Delivery Vehicles to Fight Metastatic Cancers. Curr. Drug Deliv. 2023. [Google Scholar] [CrossRef]
- Sherif, Y.A.; Harisa, I.G.; Alanazi, K.F. SLN Mediate Active Delivery of Gefitinib into A549 Cell Line: Optimization, Biosafety, and Cytotoxicity Studies. Drug Deliv. Lett. 2023, 13, 133–150. [Google Scholar]
- Wang, H.; Huang, Y. Combination therapy based on nano codelivery for overcoming cancer drug resistance. Med. Drug Discov. 2020, 6, 100024. [Google Scholar]
- Müller, A.M.; Florek, M. 5-Azacytidine/5-Azacitidine. In Small Molecules in Oncology; Springer: Berlin/Heidelberg, Germany, 2014; pp. 299–324. [Google Scholar]
- Vendetti, F.P.; Topper, M.; Huang, P.; Dobromilskaya, I.; Easwaran, H.; Wrangle, J.; Baylin, S.B.; Poirier, J.T.; Rudin, C.M. Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer. Oncotarget 2015, 6, 56. [Google Scholar] [CrossRef] [Green Version]
- Cheng, H.; Zou, Y.; Shah, C.D.; Fan, N.; Bhagat, T.D.; Gucalp, R.; Kim, M.; Verma, A.; Piperdi, B.; Spivack, S.D. First-in-human study of inhaled Azacitidine in patients with advanced non-small cell lung cancer. Lung Cancer 2021, 154, 99–104. [Google Scholar] [CrossRef]
- Sharma, A.; Shambhwani, D.; Pandey, S.; Singh, J.; Lalhlenmawia, H.; Kumarasamy, M.; Singh, S.K.; Chellappan, D.K.; Gupta, G.; Prasher, P.; et al. Advances in lung cancer treatment using nanomedicines. ACS Omega 2022, 8, 10–41. [Google Scholar] [CrossRef] [PubMed]
- Ejigah, V.; Owoseni, O.; Bataille-Backer, P.; Ogundipe, O.D.; Fisusi, F.A.; Adesina, S.K. Approaches to improve macromolecule and nanoparticle accumulation in the tumor microenvironment by the enhanced permeability and retention effect. Polymers 2022, 14, 2601. [Google Scholar] [CrossRef]
- Huang, Q.; Yang, Y.; Zhu, Y.; Chen, Q.; Zhao, T.; Xiao, Z.; Wang, M.; Song, X.; Jiang, Y.; Yang, Y.; et al. Oral Metal-Free Melanin Nanozymes for Natural and Durable Targeted Treatment of Inflammatory Bowel Disease (IBD). Small 2023, 9, 2207350. [Google Scholar] [CrossRef]
- Song, X.; Huang, Q.; Yang, Y.; Ma, L.; Liu, W.; Ou, C.; Chen, Q.; Zhao, T.; Xiao, Z.; Wang, M.; et al. Efficient Therapy of Inflammatory Bowel Disease (IBD) with Highly Specific and Durable Targeted Ta2C Modified with Chondroitin Sulfate (TACS). Adv. Mater. 2023, 2301585. [Google Scholar] [CrossRef] [PubMed]
- Huang, Q.; Liu, Z.; Yang, Y.; Yang, Y.; Huang, T.; Hong, Y.; Zhang, J.; Chen, Q.; Zhao, T.; Xiao, Z.; et al. Selenium Nanodots (SENDs) as Antioxidants and Antioxidant-Prodrugs to Rescue Islet β Cells in Type 2 Diabetes Mellitus by Restoring Mitophagy and Alleviating Endoplasmic Reticulum Stress. Adv. Sci. 2023, 10, 2300880. [Google Scholar] [CrossRef]
- Harisa, G.I.; Sherif, A.Y.; Alanazi, F.K. Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons. J. Membr. Biol. 2023, 256, 199–222. [Google Scholar] [PubMed]
- Wang, L.; Liu, G.; Hu, Y.; Gou, S.; He, T.; Feng, Q.; Cai, K. Doxorubicin-loaded polypyrrole nanovesicles for suppressing tumor metastasis through combining photothermotherapy and lymphatic system-targeted chemotherapy. Nanoscale 2022, 14, 3097–3111. [Google Scholar] [CrossRef]
- Munir, R.; Lisec, J.; Swinnen, J.V.; Zaidi, N. Lipid metabolism in cancer cells under metabolic stress. Br. J. Cancer 2019, 120, 1090–1098. [Google Scholar] [CrossRef]
- Butler, L.M.; Perone, Y.; Dehairs, J.; Lupien, L.E.; de Laat, V.; Talebi, A.; Loda, M.; Kinlaw, W.B.; Swinnen, J.V. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv. Drug Deliv. Rev. 2020, 159, 245–293. [Google Scholar] [PubMed]
- Sherif, A.Y.; Harisa, G.I.; Alanazi, F.K.; Nasr, F.A.; Alqahtani, A.S. Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line. AAPS PharmSciTech 2022, 23, 183. [Google Scholar] [CrossRef] [PubMed]
- Fan, W.; Yu, Z.; Peng, H.; He, H.; Lu, Y.; Qi, J.; Dong, X.; Zhao, W.; Wu, W. Effect of particle size on the pharmacokinetics and biodistribution of parenteral nanoemulsions. Int. J. Pharm. 2020, 586, 119551. [Google Scholar] [CrossRef] [PubMed]
- Son, G.H.; Na, Y.G.; Huh, H.W.; Wang, M.; Kim, M.K.; Han, M.G.; Byeon, J.J.; Lee, H.K.; Cho, C.W. Systemic design and evaluation of ticagrelor-loaded nanostructured lipid carriers for enhancing bioavailability and antiplatelet activity. Pharmaceutics 2019, 11, 222. [Google Scholar] [CrossRef] [Green Version]
- Sherif, A.Y.; Harisa, G.I.; Alanazi, F.K.; Nasr, F.A.; Alqahtani, A.S. PEGylated SLN as a promising approach for lymphatic delivery of gefitinib to lung cancer. Int. J. Nanomed. 2022, 17, 3287–3311. [Google Scholar] [CrossRef] [PubMed]
- Hasan, M.K.; Enomoto, K.; Kikuchi, M.; Narumi, A.; Takahashi, S.; Kawaguchi, S. Dispersion of submicron-sized SiO2/Al2O3-coated TiO2 particles and efficient encapsulation via the emulsion copolymerization of methacrylates using a thermoresponsive polymerizable nonionic surfactant. Polym. J. 2023, 55, 617–629. [Google Scholar]
- Harisa, G.I.; Sherif, A.Y.; Alanazi, F.K.; Ali, E.A.; Omran, G.A.; Nasr, F.A.; Attia, S.M.; Alqahtani, A.S. TPGS decorated NLC shift gefitinib from portal absorption into lymphatic delivery: Intracellular trafficking, biodistribution and bioavailability studies. Colloids Surf. B Biointerfaces 2023, 223, 113148. [Google Scholar] [CrossRef]
- Kesharwani, P.; Md, S.; Alhakamy, N.A.; Hosny, K.M.; Haque, A. QbD enabled azacitidine loaded liposomal nanoformulation and its in vitro evaluation. Polymers 2021, 13, 250. [Google Scholar] [CrossRef]
- Rohilla, S.; Awasthi, R.; Mehta, M.; Chellappan, D.K.; Gupta, G.; Gulati, M.; Singh, S.K.; Anand, K.; Oliver, B.G.; Dua, K. Preparation and Evaluation of Gefitinib Containing Nanoliposomal Formulation for Lung Cancer Therapy. BioNanoScience 2022, 12, 241–255. [Google Scholar] [CrossRef]
- Moura, R.B.P.; Andrade, L.M.; Alonso, L.; Alonso, A.; Marreto, R.N.; Taveira, S.F. Combination of lipid nanoparticles and iontophoresis for enhanced lopinavir skin permeation: Impact of electric current on lipid dynamics. Eur. J. Pharm. Sci. 2022, 168, 106048. [Google Scholar] [CrossRef]
- Owens, K.; Argon, S.; Yu, J.; Yang, X.; Wu, F.; Lee, S.C.; Sun, W.J.; Ramamoorthy, A.; Zhang, L.; Ragueneau-Majlessi, I. Exploring the Relationship of Drug BCS Classification, Food Effect, and Gastric pH-Dependent Drug Interactions. AAPS J. 2021, 24, 16. [Google Scholar] [PubMed]
- Perera, G.; Zipser, M.; Bonengel, S.; Salvenmoser, W.; Bernkop-Schnürch, A. Development of phosphorylated nanoparticles as zeta potential inverting systems. Eur. J. Pharm. Biopharm. 2015, 97, 250–256. [Google Scholar] [CrossRef]
- Fernandes, R.S.; Silva, J.O.; Monteiro, L.O.; Leite, E.A.; Cassali, G.D.; Rubello, D.; Cardoso, V.N.; Ferreira, L.A.; Oliveira, M.C.; de Barros, A.L. Doxorubicin-loaded nanocarriers: A comparative study of liposome and nanostructured lipid carrier as alternatives for cancer therapy. Biomed. Pharmacother. 2016, 84, 252–257. [Google Scholar] [CrossRef]
- Ghate, V.M.; Kodoth, A.K.; Shah, A.; Vishalakshi, B.; Lewis, S.A. Colloidal nanostructured lipid carriers of pentoxifylline produced by microwave irradiation ameliorates imiquimod-induced psoriasis in mice. Colloids Surf. B Biointerfaces 2019, 181, 389–399. [Google Scholar] [CrossRef]
- Ebrahimi, S.; Farhadian, N.; Karimi, M.; Ebrahimi, M. Enhanced bactericidal effect of ceftriaxone drug encapsulated in nanostructured lipid carrier against gram-negative Escherichia coli bacteria: Drug formulation, optimization, and cell culture study. Antimicrob. Resist. Infect. Control 2020, 9, 28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, X.; Zhao, L.; Almasy, L.; Garamus, V.M.; Zou, A.; Willumeit, R.; Fan, S. Preparation and characterization of 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) formulations. Int. J. Pharm. 2013, 450, 225–234. [Google Scholar] [CrossRef] [Green Version]
- Argemí, A.; Vega, A.; Subra-Paternault, P.; Saurina, J. Characterization of azacytidine/poly (l-lactic) acid particles prepared by supercritical antisolvent precipitation. J. Pharm. Biomed. Anal. 2009, 50, 847–852. [Google Scholar] [CrossRef]
- Ribeiro, M.D.M.; Arellano, D.B.; Grosso, C.R.F. The effect of adding oleic acid in the production of stearic acid lipid microparticles with a hydrophilic core by a spray-cooling process. Food Res. Int. 2012, 47, 38–44. [Google Scholar] [CrossRef]
- Nayek, S.; Raghavendra, N.; Kumar, B.S. Development of novel S PC-3 gefitinib lipid nanoparticles for effective drug delivery in breast cancer. Tissue distribution studies and cell cytotoxicity analysis. J. Drug Deliv. Sci. Technol. 2021, 61, 102073. [Google Scholar] [CrossRef]
- Alshetaili, A.S. Gefitinib loaded PLGA and chitosan coated PLGA nanoparticles with magnified cytotoxicity against A549 lung cancer cell lines. Saudi J. Biol. Sci. 2021, 28, 5065–5073. [Google Scholar] [CrossRef]
- Galvao, J.G.; Trindade, G.G.; Santos, A.J.; Santos, R.L.; Chaves Filho, A.B.; Lira, A.A.; Miyamoto, S.; Nunes, R.S. Effect of Ouratea sp. butter in the crystallinity of solid lipids used in nanostructured lipid carriers (NLCs). J. Therm. Anal. Calorim. 2016, 123, 941–948. [Google Scholar] [CrossRef]
- Lin, Y.; Yin, W.; Li, Y.; Liu, G. Influence of different solid lipids on the properties of a novel nanostructured lipid carrier containing Antarctic krill oil. Int. J. Food Sci. Technol. 2022, 57, 2886–2895. [Google Scholar] [CrossRef]
- Jansook, P.; Fülöp, Z.; Ritthidej, G.C. Amphotericin B loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carrier (NLCs): Physicochemical and solid-solution state characterizations. Drug Dev. Ind. Pharm. 2019, 45, 560–567. [Google Scholar] [CrossRef] [PubMed]
- Pandey, S.S.; Patel, M.A.; Desai, D.T.; Patel, H.P.; Gupta, A.R.; Joshi, S.V.; Shah, D.O.; Maulvi, F.A. Bioavailability enhancement of repaglinide from transdermally applied nanostructured lipid carrier gel: Optimization, in vitro and in vivo studies. J. Drug Deliv. Sci. Technol. 2020, 57, 101731. [Google Scholar] [CrossRef]
- Holder, J.E.; Ferguson, C.; Oliveira, E.; Lodeiro, C.; Trim, C.M.; Byrne, L.J.; Bertolo, E.; Wilson, C.M. The use of nanoparticles for targeted drug delivery in non-small cell lung cancer. Front. Oncol. 2023, 13, 1154318. [Google Scholar] [CrossRef]
- Almoustafa, H.A.; Alshawsh, M.A.; Al-Suede FS, R.; Alshehade, S.A.; Abdul Majid AM, S.; Chik, Z. The Chemotherapeutic Efficacy of Hyaluronic Acid Coated Polymeric Nanoparticles against Breast Cancer Metastasis in Female NCr-Nu/Nu Nude Mice. Polymers 2023, 15, 284. [Google Scholar] [CrossRef]
- Makeen, H.A.; Mohan, S.; Al-Kasim, M.A.; Attafi, I.M.; Ahmed, R.A.; Syed, N.K.; Sultan, M.H.; Al-Bratty, M.; Alhazmi, H.A.; Safhi, M.M.; et al. Gefitinib loaded nanostructured lipid carriers: Characterization, evaluation and anti-human colon cancer activity in vitro. Drug Deliv. 2020, 27, 622–631. [Google Scholar] [CrossRef] [Green Version]
- De, K. Decapeptide modified doxorubicin loaded solid lipid nanoparticles as targeted drug delivery system against prostate cancer. Langmuir 2021, 37, 13194–13207. [Google Scholar] [CrossRef]
- Kashyap, K.; Handa, M.; Shukla, R. Azacitidine loaded PLGA nanoparticles and their dual release mechanism. Curr. Nanomed. (Former. Recent Pat. Nanomed.) 2020, 10, 280–289. [Google Scholar] [CrossRef]
- Zhou, W.; Jia, Y.; Liu, Y.; Chen, Y.; Zhao, P. Tumor Microenvironment-Based Stimuli-Responsive Nanoparticles for Controlled Release of Drugs in Cancer Therapy. Pharmaceutics 2022, 14, 2346. [Google Scholar] [CrossRef]
- Zhang, C.; Peng, F.; Liu, W.; Wan, J.; Wan, C.; Xu, H.; Lam, C.W.; Yang, X. Nanostructured lipid carriers as a novel oral delivery system for triptolide: Induced changes in pharmacokinetics profile associated with reduced toxicity in male rats. Int. J. Nanomed. 2014, 9, 1049–1063. [Google Scholar]
- Zhang, J.; Li, S.; An, F.F.; Liu, J.; Jin, S.; Zhang, J.C.; Wang, P.C.; Zhang, X.; Lee, C.S.; Liang, X.J. Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release. Nanoscale 2015, 7, 13503–13510. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Salvi, V.R.; Pawar, P. Nanostructured lipid carriers (NLC) system: A novel drug targeting carrier. J. Drug Deliv. Sci. Technol. 2019, 51, 255–267. [Google Scholar] [CrossRef]
- Wang, J.; Wang, F.; Li, X.; Zhou, Y.; Wang, H.; Zhang, Y. Uniform carboxymethyl chitosan-enveloped Pluronic F68/poly (lactic-co-glycolic acid) nano-vehicles for facilitated oral delivery of gefitinib, a poorly soluble antitumor compound. Colloids Surf. B Biointerfaces 2019, 177, 425–432. [Google Scholar] [CrossRef] [PubMed]
- Huang, Y.; Dai, Y.; Wen, C.; He, S.; Shi, J.; Zhao, D.; Wu, L.; Zhou, H. circSETD3 contributes to acquired resistance to gefitinib in non-small-cell lung cancer by targeting the miR-520h/ABCG2 pathway. Mol. Ther. Nucleic Acids 2020, 21, 885–899. [Google Scholar] [CrossRef]
- Sherif, A.Y.; Harisa, G.I.; Shahba, A.A.; Alanazi, F.K.; Qamar, W. Optimization of Gefitinib-Loaded Nanostructured Lipid Carrier as a Biomedical Tool in the Treatment of Metastatic Lung Cancer. Molecules 2023, 28, 448. [Google Scholar] [CrossRef]
- Abdolahpour, S.; Mahdieh, N.; Jamali, Z.; Akbarzadeh, A.; Toliyat, T.; Paknejad, M. Development of doxorubicin-loaded nanostructured lipid carriers: Preparation, characterization, and in vitro evaluation on MCF-7 cell line. BioNanoScience 2017, 7, 32–39. [Google Scholar] [CrossRef]
- Zhang, X.-G.; Miao, J.; Dai, Y.-Q.; Du, Y.-Z.; Yuan, H.; Hu, F.-Q. Reversal activity of nanostructured lipid carriers loading cytotoxic drug in multi-drug resistant cancer cells. Int. J. Pharm. 2008, 361, 239–244. [Google Scholar] [CrossRef]
- Shah, P.; Chavda, K.; Vyas, B.; Patel, S. Formulation development of linagliptin solid lipid nanoparticles for oral bioavailability enhancement: Role of P-gp inhibition. Drug Deliv. Transl. Res. 2021, 11, 1166–1185. [Google Scholar] [CrossRef]
- Tanaudommongkon, I.; Tanaudommongkon, A.; Prathipati, P.; Nguyen, J.T.; Keller, E.T.; Dong, X. Curcumin nanoparticles and their cytotoxicity in docetaxel-resistant castration-resistant prostate cancer cells. Biomedicines 2020, 8, 253. [Google Scholar] [CrossRef]
- Hiremath, C.G.; Heggnnavar, G.B.; Kariduraganavar, M.Y.; Hiremath, M.B. Co-delivery of paclitaxel and curcumin to foliate positive cancer cells using Pluronic-coated iron oxide nanoparticles. Prog. Biomater. 2019, 8, 155–168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tran, N.; Mulet, X.; Hawley, A.M.; Hinton, T.M.; Mudie, S.T.; Muir, B.W.; Giakoumatos, E.C.; Waddington, L.J.; Kirby, N.M.; Drummond, C.J. Nanostructure and cytotoxicity of self-assembled monoolein–capric acid lyotropic liquid crystalline nanoparticles. RSC Adv. 2015, 5, 26785–26795. [Google Scholar] [CrossRef]
- Wu, K.W.; Sweeney, C.; Dudhipala, N.; Lakhani, P.; Chaurasiya, N.D.; Tekwani, B.L.; Majumdar, S. Primaquine loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE): Effect of lipid matrix and surfactant on drug entrapment, in vitro release, and ex vivo hemolysis. AAPS PharmSciTech 2021, 22, 240. [Google Scholar] [CrossRef] [PubMed]
Acquity UPLC (H10UPH) | Acquity TQD MS (QBB1203) | ||
---|---|---|---|
Isocratic mobile phase | 50% acetonitrile: 50%, 0.1% formic acid (pH: 3.2) | ESI | Positive ESI |
Nitrogen (drying gas; 350 °C) at 100 L/H flow rate | |||
Flow rate: 0.2 mL/min | Cone gas: 100 L/H flow rate | ||
Injection volume: 5.0 μL | The voltage of extractor: 3.0 (V) | ||
Eclipse plus-C18 column | 50 mm long | The voltage of RF lens: 0.1 (V) | |
2.1 mm i.d. | Capillary voltage: 4 KV | ||
3.5 μm particle size | Collision cell | Argon gas (collision gas) at 0.14 mL/min flow rate | |
T: 22.0 ± 2.0 °C | Mode | MRM |
Formulation Code * | Lipid Phase | Aqueous Phase | |||||
---|---|---|---|---|---|---|---|
SA | OA | GEF | AZT | P-188 | TPGS | Water | |
Plain-NLC | 450 | 150 | 0 | 0 | 120 | 7.5 | 14,272.5 |
GEF-NLC | 450 | 150 | 15 | 0 | 120 | 7.5 | 14,257.5 |
AZT-NLC | 450 | 150 | 0 | 15 | 120 | 7.5 | 14,257.5 |
GEF-AZT-NLC | 450 | 150 | 15 | 15 | 120 | 7.5 | 14,242.5 |
Measured Parameter * | Plain-NLC | GEF-NLC | AZT-NLC | GEF-AZT-NLC | |
---|---|---|---|---|---|
Particle size (nm) | 258.0 ± 11.2 | 272.1 ± 21.3 | 235.1 ± 11.8 | 268.9 ± 23.6 | |
Polydispersity index | 0.171 ± 0.01 | 0.129 ± 0.09 | 0.149 ± 0.05 | 0.204 ± 0.08 | |
Zeta potential (mV) | −31.1 ± 3.3 | −23.9 ± 1.2 | −17.0 ± 2.0 | −15.3 ± 1.2 | |
Drug content (mg/mL) | GEF | --- | 1.01 ± 0.2 | --- | 1.04 ± 0.3 |
AZT | --- | --- | 1.03 ± 0.5 | 0.98 ± 0.5 | |
Entrapment efficiency (%) | GEF | --- | 97.2 ± 0.8 | --- | 96.7 ± 0.6 |
AZT | --- | --- | 96.8 ± 1.1 | 98.3 ± 0.9 |
Anticancer Agent | IC50 (μg/mL) * |
---|---|
GEF | 11.14 ± 0.44 |
AZT | 4.89 ± 0.22 |
GEF + AZT | 4.31 ± 0.10 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Elzayat, E.M.; Sherif, A.Y.; Nasr, F.A.; Attwa, M.W.; Alshora, D.H.; Ahmad, S.F.; Alqahtani, A.S. Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles. Materials 2023, 16, 5364. https://doi.org/10.3390/ma16155364
Elzayat EM, Sherif AY, Nasr FA, Attwa MW, Alshora DH, Ahmad SF, Alqahtani AS. Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles. Materials. 2023; 16(15):5364. https://doi.org/10.3390/ma16155364
Chicago/Turabian StyleElzayat, Ehab M., Abdelrahman Y. Sherif, Fahd A. Nasr, Mohamed W. Attwa, Doaa H. Alshora, Sheikh F. Ahmad, and Ali S. Alqahtani. 2023. "Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles" Materials 16, no. 15: 5364. https://doi.org/10.3390/ma16155364
APA StyleElzayat, E. M., Sherif, A. Y., Nasr, F. A., Attwa, M. W., Alshora, D. H., Ahmad, S. F., & Alqahtani, A. S. (2023). Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles. Materials, 16(15), 5364. https://doi.org/10.3390/ma16155364