Bhushan S. Pattni,† Vladimir V. Chupin,‡ and Vladimir P. Torchilin*,†,§,∥ †Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts 02115, United States ‡Laboratory for Advanced Studies of Membrane Proteins, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia

New Developments in Liposomal Drug Delivery.

Pentacyclic triterpenes are secondary plant metabolites widespread in fruit peel, leaves and stem bark. In particular the lupane-, oleanane-, and ursane triterpenes display various pharmacological effects while being devoid of prominent toxicity. Therefore, these triterpenes are promising leading compounds for the development of new multi-targeting bioactive agents. Screening of 39 plant materials identified triterpene rich (> 0.1% dry matter) plant parts. Plant materials with high triterpene concentrations were then used to obtain dry extracts by accelerated solvent extraction resulting in a triterpene content of 50 - 90%. Depending on the plant material, betulin (birch bark), betulinic acid (plane bark), oleanolic acid (olive leaves, olive pomace, mistletoe sprouts, clove flowers), ursolic acid (apple pomace) or an equal mixture of the three triterpene acids (rosemary leaves) are the main components of these dry extracts. They are quantitatively characterised plant extracts supplying a high concentration of actives and therefore can be used for development of phytopharmaceutical formulations.

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Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts.

Today cancer treatment is not only a question of eliminating cancer cells by induction of cell death. New therapeutic strategies also include targeting the tumour microenvironment, avoiding angiogenesis, modulating the immune response or the chronic inflammation that is often associated with cancer. Furthermore, the induction of redifferentiation of dedifferentiated cancer cells is an interesting aspect in developing new therapy strategies. Plants provide a broad spectrum of potential drug substances for cancer therapy with multifaceted effects and targets. Pentacyclic triterpenes are one group of promising secondary plant metabolites. This review summarizes the potential of triterpenes belonging to the lupane, oleanane or ursane group, to treat cancer by different modes of action. Since Pisha et al. reported in 1995 that betulinic acid is a highly promising anticancer drug after inducing apoptosis in melanoma cell lines in vitro and in vivo, experimental work focused on the apoptosis inducing mechanisms of betulinic acid and other triterpenes. The antitumour effects were subsequently confirmed in a series of cancer cell lines from other origins, for example breast, colon, lung and neuroblastoma. In addition, in the last decade many studies have shown further effects that justify the expectation that triterpenes are useful to treat cancer by several modes of action. Thus, triterpene acids are known mainly for their antiangiogenic effects as well as their differentiation inducing effects. In particular, lupane-type triterpenes, such as betulin, betulinic acid and lupeol, display anti-inflammatory activities which often accompany immune modulation. Triterpene acids as well as triterpene monoalcohols and diols also show an antioxidative potential. The pharmacological potential of triterpenes of the lupane, oleanane or ursane type for cancer treatment seems high; although up to now no clinical trial has been published using these triterpenes in cancer therapy. They provide a multitarget potential for coping with new cancer strategies. Whether this is an effective approach for cancer treatment has to be proven. Because various triterpenes are an increasingly promising group of plant metabolites, the utilisation of different plants as their sources is of interest. Parts of plants, for example birch bark, rosemary leaves, apple peel and mistletoe shoots are rich in triterpenes and provide different triterpene compositions.

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Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy.

Liposomes as carriers of hydrophilic small molecule drugs: strategies to enhance encapsulation and delivery.

https://digital.library.unt.edu/ark:/67531/metadc284556/m2/1/high_res_d/1-s2.0-S0304383514000421-main.pdf

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

Mistletoe (Viscum album L.) contains the triterpene acids oleanolic acid (OA) and betulinic acid (BA), which were found to have anti-tumour properties. In this study, the solubilities of OA and BA were studied in water (up to 0.02 microg/mL in each case) and in alkaline solutions of 10 mM trisodium phosphate (pH 11.5; OA: 77.2 microg/mL; BA: 40.1 microg/mL). Furthermore, triterpene acids were quantified in aqueous mistletoe extracts (pH 7.3; drug to extract ratio 1:25). OA (1.1 microg/mL) and BA (0.9 microg/mL) were extracted with a yield of less than 5%. Preparing plant extracts with basic pH values resulted in a triterpene acid content of 9.3 microg/mL OA and 5.2 microg/mL BA (pH 12.1), reaching neither the solubility limits nor a complete extraction of the plant material. The triterpene acid content of neutral plant extracts above the solubility limit could be due to interactions with biocolloids. Interaction studies were performed by gel permeation chromatography. Different mechanisms of the dissolution at pH 7.3 and pH 10.2 are discussed.

Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L

Membrane interactions of ternary phospholipid/cholesterol bilayers and encapsulation efficiencies of a RIP II protein

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Karin Winkler

Papers

Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L

Membrane interactions of ternary phospholipid/cholesterol bilayers and encapsulation efficiencies of a RIP II protein

Surface rheology of monolayers of phospholipids and cholesterol measured with axisymmetric drop shape analysis

Surface rheology and phase transitions of monolayers of phospholipid/cholesterol mixtures.

Characterization of membrane vesicles in plant extracts