2. Academic Validation
  3. Ivermectin Enhanced Antitumor Activity of Resiquimod in a Co-Loaded Squalene Emulsion

Ivermectin Enhanced Antitumor Activity of Resiquimod in a Co-Loaded Squalene Emulsion

  • J Pharm Sci. 2022 Jun 11;S0022-3549(22)00249-0. doi: 10.1016/j.xphs.2022.06.005.
Zhongkun Zhang 1,  Jimmy Chun-Tien Kuo 2,  Chi Zhang 3,  Yirui Huang 4,  Robert J Lee 5
Affiliations

Affiliations

  • 1 Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, 500 W 12th Avenue, Columbus, OH, 43210, USA. Electronic address: zhang.5763@osu.edu.
  • 2 Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, 500 W 12th Avenue, Columbus, OH, 43210, USA. Electronic address: kuo.249@osu.edu.
  • 3 Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, 500 W 12th Avenue, Columbus, OH, 43210, USA. Electronic address: zhang.9395@osu.edu.
  • 4 Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, 500 W 12th Avenue, Columbus, OH, 43210, USA.
  • 5 Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, 500 W 12th Avenue, Columbus, OH, 43210, USA. Electronic address: lee.1339@osu.edu.
PMID: 35697319 DOI: 10.1016/j.xphs.2022.06.005
Abstract

Immunogenic cell death (ICD) plays an important role in sensitizing tumor cells to antigen-presenting cells followed by antitumor immunity. However, a successful antitumor response by ICD requires both apoptotic tumor microenvironments and activated immune systems. Ivermectin (IVM) has been shown to induce cell Apoptosis through Autophagy which can be a great candidate for ICD therapy. However, a single treatment of IVM-free drug is not an ideal Anticancer therapy due to its anti-inflammatory effects and cytotoxicity. In the present study, IVM was shown to enhance the ICD process in addition to the treatment of resiquimod (R848), a TLR7/8 agonist, when co-loaded in a squalene-based nanoemulsion (NE). R848-IVM co-loaded NE was developed and characterized in vitro. Antitumor activity of R848-IVM NE was also evaluated in vitro and in vivo. R848-IVM NE exhibited long-term stability and reduced cytotoxicity by IVM. In vivo studies demonstrated that IVM significantly augments the ICD by upregulating CD8a and releasing HMGB1 in tumor tissue, which could enhance R848-driven antitumor immunity. R848-IVM NE treatment showed strong antitumor activity with over 80% tumor growth inhibition, suggesting a potential combination therapy of systemic co-delivering IVM with TLR agonists against solid Cancer.

Keywords

Ivermectin; Nanoemulsions; Solid Tumors; TLR Agonists.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z