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Gene Expression Effects of the Delivery of SN-38 via Poly(D-L-lactide-co-caprolactone) Nanoparticles Comprising Dense and Collapsed Poloxamer Coronae

Journal of Pharmaceutical Innovation volume 18, pages 585–593 (2023)Cite this article

Abstract

Purpose

SN-38 is an antineoplastic drug with a three orders of magnitude higher activity than its prodrug, irinotecan, a common chemotherapeutic of choice in the treatment of colorectal cancer. A considerable number of genes are known to alter their expression under the influence of free SN-38, but no studies have looked at the gene expression effects of SN-38 delivered via poly(D-L-lactide-co-caprolactone) (PLCL) nanoparticles yet.

Method

We evaluated changes to expression levels of genes encoding for ubiquitin D (UBD), fibroblast growth factor 3 (FGF3), histone (HIST), and regulator of cell cycle (RGCC) in SW-480 colon cancer cells in response to free SN-38 and two types of poloxamer-coated PLCL (PEO-PPO-PEO/PLCL) nanoparticles as carriers for SN-38, containing different conformations of the hydrophilic stealth corona: dense or collapsed.

Results

Both the free drug and the two drug-loaded nanoformulations upregulated UBD and RGCC and downregulated FGF3 and HIST, which was consistent with the pharmacological activity of SN-38. Still, there was a clear difference in gene expression levels in SW-480 cells depending on whether they were challenged with free SN-38 or with nanoparticles loaded with SN-38. Most critically, the delivery of SN-38 with the nanoparticles prolonged its mode of action and, in the case of genes such as UBD, FGF3, and HIST, provided for a more intense effect on gene expression alteration than that achieved by the drug alone.

Conclusions

Nanoparticles comprising the collapsed PEO-PPO-PEO corona produced a more intense effect on gene expression alteration than the nanoparticles with the dense PEO-PPO-PEO corona.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Biopharmacy, Pharmacy Division, Faculty of Medicine, University of Prishtina “Hasan Prishtina” St. Blvd. i Dëshmorëve n.n., 10000, Prishtina, Republic of Kosovo

    Rozafa Koliqi & Arlinda Daka Grapci

  2. Department of Pharmaceutical Chemistry, Pharmacy Division, Faculty of Medicine, University of Prishtina “Hasan Prishtina” St. Blvd. i Dëshmorëve n.n., 10000, Prishtina, Republic of Kosovo

    Pranvera Breznica Selmani

  3. TardigradeNano LLC, Irvine, CA, USA

    Vuk Uskoković

  4. Department of Mechanical Engineering, San Diego State University, San Diego, CA, USA

    Vuk Uskoković

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  1. Rozafa Koliqi
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Correspondence to Vuk Uskoković.

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Koliqi, R., Grapci, A.D., Selmani, P.B. et al. Gene Expression Effects of the Delivery of SN-38 via Poly(D-L-lactide-co-caprolactone) Nanoparticles Comprising Dense and Collapsed Poloxamer Coronae. J Pharm Innov 18, 585–593 (2023). https://doi.org/10.1007/s12247-022-09672-8

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