Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy

Fahmy, Sherif Ashraf; Sedky, Nada K.; Hassan, Hatem A. F. M.; Abdel-Kader, Nour M.; Mahdy, Noha Khalil; Amin, Muhammad Umair; Preis, Eduard; Bakowsky, Udo

doi:10.3390/pharmaceutics16101282

Open AccessArticle

Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy

by

Sherif Ashraf Fahmy

^1,2,*,†

,

Nada K. Sedky

^3,†

,

Hatem A. F. M. Hassan

^4,5

,

Nour M. Abdel-Kader

^3,6

,

Noha Khalil Mahdy

⁵

,

Muhammad Umair Amin

²,

Eduard Preis

²

and

Udo Bakowsky

^2,*

¹

Department of Chemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, Egypt

²

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany

³

Department of Biochemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, Egypt

⁴

Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, Kent ME4 4TB, UK

⁵

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt

⁶

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo 11566, Egypt

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Pharmaceutics 2024, 16(10), 1282; https://doi.org/10.3390/pharmaceutics16101282

Submission received: 30 August 2024 / Revised: 25 September 2024 / Accepted: 27 September 2024 / Published: 30 September 2024

(This article belongs to the Special Issue The State-of-the-art in Improving the Antitumor Efficacy of Platinum Drugs)

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Abstract

Carboplatin (Cp) is a potent chemotherapeutic agent, but its effectiveness is constrained by its associated side effects. Frankincense, an oleo-gum resin from the Boswellia sacra tree, has demonstrated cytotoxic activity against cancer cells. This study explored the synergistic potential of nanoparticles formulated from Boswellia sacra methanolic extract (BME), to enhance the therapeutic efficacy of Cp at reduced doses. Nanoparticles were prepared via the nanoprecipitation method, loaded with Cp, and coated with positively charged chitosan (CS) for enhanced cell interaction, yielding Cp@CS/BME NPs with an average size of 160.2 ± 4.6 nm and a zeta potential of 12.7 ± 1.5 mV. In vitro release studies revealed a pH-sensitive release profile, with higher release rates at pH 5.4 than at pH 7.4, highlighting the potential for targeted drug delivery in acidic tumor environments. In vitro studies on HT-29 and Caco-2 colorectal cancer cell lines demonstrated the nanoformulation’s ability to significantly increase Cp uptake and cytotoxic activity. Apoptosis assays further confirmed increased induction of cell death with Cp@CS/BME NPs. Cell-cycle analysis revealed that treatment with Cp@CS/BME NPs led to a significant increase in the sub-G1 phase, indicative of enhanced apoptosis, and a marked decrease in the G1-phase population coupled with an increased G2/M-phase arrest in both cell lines. Further gene expression analysis demonstrated a substantial downregulation of the anti-apoptotic gene Bcl-2 and an upregulation of the pro-apoptotic genes Bax, PUMA, and BID following treatment with Cp@CS/BME NPs. Thus, this study presents a promising and innovative strategy for enhancing the therapeutic efficacy of chemotherapeutic agents using naturally derived ingredients while limiting the side effects.

Keywords: colorectal cancer; chemotherapy; nanomedicine; nanoprecipitation; pH-sensitive release

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MDPI and ACS Style

Fahmy, S.A.; Sedky, N.K.; Hassan, H.A.F.M.; Abdel-Kader, N.M.; Mahdy, N.K.; Amin, M.U.; Preis, E.; Bakowsky, U. Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy. Pharmaceutics 2024, 16, 1282. https://doi.org/10.3390/pharmaceutics16101282

AMA Style

Fahmy SA, Sedky NK, Hassan HAFM, Abdel-Kader NM, Mahdy NK, Amin MU, Preis E, Bakowsky U. Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy. Pharmaceutics. 2024; 16(10):1282. https://doi.org/10.3390/pharmaceutics16101282

Chicago/Turabian Style

Fahmy, Sherif Ashraf, Nada K. Sedky, Hatem A. F. M. Hassan, Nour M. Abdel-Kader, Noha Khalil Mahdy, Muhammad Umair Amin, Eduard Preis, and Udo Bakowsky. 2024. "Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy" Pharmaceutics 16, no. 10: 1282. https://doi.org/10.3390/pharmaceutics16101282

APA Style

Fahmy, S. A., Sedky, N. K., Hassan, H. A. F. M., Abdel-Kader, N. M., Mahdy, N. K., Amin, M. U., Preis, E., & Bakowsky, U. (2024). Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy. Pharmaceutics, 16(10), 1282. https://doi.org/10.3390/pharmaceutics16101282

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Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy

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