title: Betulin complex in γ-cyclodextrin derivatives: properties and antineoplasic activities in in vitro and in vivo tumor models.
abstract: Given the present high incidence of melanoma and skin cancer, interest in potential drugs of plant origin has increased significantly. Pentacyclic lupane-type triterpenes are widely distributed in plants, offering numerous pharmacological benefits. Betulin is an important compound in the bark of Betula pendula Roth and has important therapeutic properties, including antitumor activities. Its biological effect is limited by its poor water solubility, which can be improved by cyclodextrin complexation. The best results have been obtained by using a novel cyclodextrin derivative, octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonate)]-γ-CD. The complexes between betulin and the previously mentioned cyclodextrin were analyzed by scanning electron microscopy (SEM)and differential scanning calorimetry (DSC) and pharmacologically evaluated in vitro (MTT and immunocytochemistry tests) and in vivo in C57BL/6J mice. The solubility of betulin is improved by cyclodextrin complexation, which creates a stable complex that improves the in vitro and in vivo properties of the active compound.
authors.affiliation: Faculty of Pharmacy, University of Medicine and Pharmacy, 2 Eftimie Murgu, Timisoara 300041, Romania. cadehelean@umft.ro.
authors.forename: Codruta
authors.initials: C
authors.lastname: Soica
authors.forename: Cristina
authors.initials: C
authors.lastname: Dehelean
authors.forename: Corina
authors.initials: C
authors.lastname: Danciu
authors.forename: Hai Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wenz
authors.forename: Rita
authors.initials: R
authors.lastname: Ambrus
authors.forename: Florina
authors.initials: F
authors.lastname: Bojin
authors.forename: Mariana
authors.initials: M
authors.lastname: Anghel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004338:Drug Combinations; D005434:Flow Cytometry; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D047408:gamma-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D053143:Caspase 2; D004338:Drug Combinations; D014315:Triterpenes; D047408:gamma-Cyclodextrins; C002503:betulin; D000094062:Betulinic Acid