Evolution from small molecule to nano-drug delivery systems: An emerging approach for cancer therapy of ursolic acid

Shao, Jingwei; Fang, Yifan; Zhao, Rui; Chen, Fangmin; Yang, Mingyue; Jiang, Jiali; Chen, Zixuan; Yuan, Xiaotian; Lee, Jia

doi:10.1016/j.ajps.2020.03.001

Cited by 45 publications

(31 citation statements)

References 128 publications

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“…The poor solubility of compounds translates into a short half-life in blood circulation, low bioavailability, and the insufficient effectiveness of therapy [ 25 , 26 ]. On the other hand, after intravenous administration, the low-molecular-weight triterpenoids can undergo non-specific distribution in the body [ 27 ]. Pharmacological effects may be enhanced by the development of novel drug delivery systems (DDSs) based on nanocarriers.…”

Section: Drug Delivery Systemsmentioning

confidence: 99%

“…Despite the continuous development and undeniable overall benefits of the modern nanoformulations used in DDSs, there are still many unknowns and challenges that limit their widespread use. The current challenges for scientists in designing and manufacturing nanoformulations are related to (i) the properties of the used biomaterials, (ii) production limitations, (iii) loading capacity, (iv) stability, (v) toxicity, and (vi) biological barriers [ 27 , 30 , 48 ]. The properties of biomaterials, like charge of surface group or biodegradability, can affect their cytotoxicity, biocompatibility, and membrane permeability [ 29 ].…”

Section: Drug Delivery Systemsmentioning

confidence: 99%

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Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

2021

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The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many natural phytochemicals have anticancer potential. Pentacyclic triterpenoids, characterized by six- and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom. Among the known natural triterpenoids, we can distinguish lupane-, oleanane-, and ursane-types. Pentacyclic triterpenoids are known to have many biological activities, e.g., anti-inflammatory, antibacterial, hepatoprotective, immunomodulatory, antioxidant, and anticancer properties. Unfortunately, they are also characterized by poor water solubility and, hence, low bioavailability. These pharmacological properties may be improved by both introducing some modifications to their native structures and developing novel delivery systems based on the latest nanotechnological achievements. The development of nanocarrier-delivery systems is aimed at increasing the transport capacity of bioactive compounds by enhancing their solubility, bioavailability, stability in vivo and ensuring tumor-targeting while their toxicity and risk of side effects are significantly reduced. Nanocarriers may vary in sizes, constituents, shapes, and surface properties, all of which affect the ultimate efficacy and safety of a given anticancer therapy, as presented in this review. The presented results demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids.

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Section: Drug Delivery Systemsmentioning

confidence: 99%

Section: Drug Delivery Systemsmentioning

confidence: 99%

Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

2021

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“…Recently, traditional Chinese medicine, especially involving natural products, has attracted increasing attention as antitumor therapy. Ursolic acid (UA), a pentacyclic triterpenoid, can be isolated from various natural sources, such as Salvia officinalis , Rosmarinus officinalis , and Sanguisorba officinalis (Shao et al., 2020 ). It has been reported that UA has various pharmacological properties, including antitumor, anti-inflammatory, antibacterial, and antioxidant effects (Mlala et al., 2019 ; Shao et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Ursolic acid (UA), a pentacyclic triterpenoid, can be isolated from various natural sources, such as Salvia officinalis , Rosmarinus officinalis , and Sanguisorba officinalis (Shao et al., 2020 ). It has been reported that UA has various pharmacological properties, including antitumor, anti-inflammatory, antibacterial, and antioxidant effects (Mlala et al., 2019 ; Shao et al., 2020 ). Previous studies have shown that UA can significantly inhibit proliferation and induce apoptosis of different types of malignant tumor cells, including those of breast cancer, hepatocarcinoma, and gastric cancer (Zhang et al., 2013 , 2016a ; Liu et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

A novel redox-responsive ursolic acid polymeric prodrug delivery system for osteosarcoma therapy

et al. 2021

Drug Delivery

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Ursolic acid (UA), found widely in nature, exerts effective anti-tumoral activity against various malignant tumors. However, the low water solubility and poor bioavailability of UA have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive UA polymeric prodrug was synthesized by conjugating UA to polyethylene glycol using a disulfide bond. This formulation can self-assemble into micelles (U-SS-M) in aqueous solutions to produce small size micelles ($62.5 nm in diameter) with high drug loading efficiency ($16.7%) that exhibit pH and reduction dual-sensitivity. The cell and animal studies performed using the osteosarcoma MG-63 cell line and MG-63 cancer xenograft mice as the model systems consistently confirmed that the U-SS-M formulation could significantly prolong the circulation in blood and favor accumulation in tumor tissue. Targeted accumulation allows the U-SS-M to be effectively internalized by cancer cells, where the rapid release of UA is favored by a glutathione-rich and acidic intracellular environment, and ultimately achieves potent antitumor efficacy.

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“…Cervical cancer [167], breast cancer [168], prostate cancer, lung cancer, hepatocellular carcinoma [169], gall bladder carcinoma, melanoma [170] Gold-ursolic acid into PLGA NP, long-circulating and pH-sensitive liposomes [171], PEG modified liposome [172], ursolic acid-loaded chitosan NP [173], pH-sensitive mesoporous silica NP CD, cyclodextrin; NP, nanoparticle; PCL, polycaprolactone; PEG, polyethylene glycol; PLA, poly(lactide); PLGA, poly lactic-co-glycolic acid; PVP, poly(vinyl pyrrolidone); QD, quantum dot; SLN, solid lipid NP; TPGS, tocopheryl polyethylene glycol 1000 succinate.…”

Section: Ursolic Acidmentioning

confidence: 99%

Emerging Nanopharmaceuticals and Nanonutraceuticals in Cancer Management

et al. 2020

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Nanotechnology is the science of nanoscale, which is the scale of nanometers or one billionth of a meter. Nanotechnology encompasses a broad range of technologies, materials, and manufacturing processes that are used to design and/or enhance many products, including medicinal products. This technology has achieved considerable progress in the oncology field in recent years. Most chemotherapeutic agents are not specific to the cancer cells they are intended to treat, and they can harm healthy cells, leading to numerous adverse effects. Due to this non-specific targeting, it is not feasible to administer high doses that may harm healthy cells. Moreover, low doses can cause cancer cells to acquire resistance, thus making them hard to kill. A solution that could potentially enhance drug targeting and delivery lies in understanding the complexity of nanotechnology. Engineering pharmaceutical and natural products into nano-products can enhance the diagnosis and treatment of cancer. Novel nano-formulations such as liposomes, polymeric micelles, dendrimers, quantum dots, nano-suspensions, and gold nanoparticles have been shown to enhance the delivery of drugs. Improved delivery of chemotherapeutic agents targets cancer cells rather than healthy cells, thereby preventing undesirable side effects and decreasing chemotherapeutic drug resistance. Nanotechnology has also revolutionized cancer diagnosis by using nanotechnology-based imaging contrast agents that can specifically target and therefore enhance tumor detection. In addition to the delivery of drugs, nanotechnology can be used to deliver nutraceuticals like phytochemicals that have multiple properties, such as antioxidant activity, that protect cells from oxidative damage and reduce the risk of cancer. There have been multiple advancements and implications for the use of nanotechnology to enhance the delivery of both pharmaceutical and nutraceutical products in cancer prevention, diagnosis, and treatment.

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Evolution from small molecule to nano-drug delivery systems: An emerging approach for cancer therapy of ursolic acid

Cited by 45 publications

References 128 publications

Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

A novel redox-responsive ursolic acid polymeric prodrug delivery system for osteosarcoma therapy

Emerging Nanopharmaceuticals and Nanonutraceuticals in Cancer Management

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