Steady Augmentation of Anti-Osteoarthritic Actions of Rapamycin by Liposome-Encapsulation in Collaboration with Low-Intensity Pulsed Ultrasound

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2020 Jun 18

PMID 32547027

Citations 20

Authors

Chung-Hwan Chen

Shyh Ming Kuo

Yin-Chun Tien

Po-Chih Shen

Yi-Wen Kuo

Han Hsiang Huang

Affiliations

Soon will be listed here.

Abstract

Introduction: Rapamycin has been considered as a potential treatment for osteoarthritis (OA). Drug carriers fabricated from liposomes can prolong the effects of drugs and reduce side effects of drugs. Low-intensity pulsed ultrasound (LIPUS) has been found to possess anti-OA effects.

Materials And Methods: The anti-osteoarthritic effects of liposome-encapsulated rapamycin (L-rapa) combined with LIPUS were examined by culture of normal and OA chondrocytes in alginate beads and further validated in OA prone Dunkin-Hartley guinea pigs.

Results: L-rapa with LIPUS largely up-regulated aggrecan and type II collagen mRNA in human OA chondrocytes (HOACs). L-rapa with LIPUS caused significant enhancement in proteoglycan and type II collagen production in HOACs. Large decreases in both MMP-13 and IL-6 proteins were found in the HOACs exposed to L-rapa with LIPUS. Intra-articular injection of 40 μL L-rapa at both 5 μM and 50 μM twice a week combined with LIPUS thrice a week for 8 weeks significantly increased GAGs and type II collagen in the cartilage of knee. Results on OARSI score showed that intra-articular injection of 5 μM L-rapa with LIPUS displayed the greatest anti-OA effects. Immunohistochemistry revealed that L-rapa with or without LIPUS predominantly reduced MMP-13 in vivo. The values of complete blood count and serum biochemical examinations remained in the normal ranges after the injections with or without LIPUS. These data indicated that intra-articular injection of L-rapa collaborated with LIPUS is not only effective against OA but a safe OA therapy.

Conclusion: Taken together, L-rapa combined with LIPUS possessed the most consistently and effectively anabolic and anti-catabolic effects in HOACs and the spontaneous OA guinea pigs. This study evidently revealed that liposome-encapsulation collaborated with LIPUS is able to reduce the effective dose and administration frequency of rapamycin and further stably reinforce its therapeutic actions against OA.

Citing Articles

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Inhibition of mTORC1 by rapamycin results in feedback activation of Akt and aggravates hallmarks of osteoarthritis in female mice and non-human primates.

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Zhou J, Ning E, Lu L, Zhang H, Yang X, Hao Y Front Med (Lausanne). 2024; 11:1292473.

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Jia W, Zhou Z, Zhan W J Funct Biomater. 2023; 14(10).

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