SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene: Lamellarity and Drug-Loading as Key Features for a Rational Drug Delivery Design

被引:34
作者
Di Sotto, Antonella [1 ]
Paolicelli, Patrizia [2 ]
Nardoni, Martina [2 ]
Abete, Lorena [1 ]
Garzoli, Stefania [2 ]
Di Giacomo, Silvia [1 ]
Mazzanti, Gabriela [1 ]
Casadei, Maria Antonietta [2 ]
Petralito, Stefania [2 ]
机构
[1] Sapienza Univ Rome, Dept Physiol & Pharmacol V Erspamer, Ple Aldo Moro 5, I-00185 Rome, Italy
[2] Sapienza Univ Rome, Dept Chem & Technol Drugs, Ple Aldo Moro 5, I-00185 Rome, Italy
关键词
lipophilic compound; caryophyllene sesquiterpene; antiproliferative activity; liposomes; lamellarity; drug loading; CHOLESTEROL; OXIDE; BACTERIAL; DOXORUBICIN; INHIBITION; ANTICANCER;
D O I
10.3390/pharmaceutics10040274
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The natural sesquiterpene beta-caryophyllene (CRY) has been highlighted to possess interesting pharmacological potentials, particularly due to its chemopreventive and analgesic properties. However, the poor solubility of this sesquiterpene in aqueous fluids can hinder its uptake into cells, resulting in inconstant responses of biological systems, thus limiting its application. Therefore, identifying a suitable pharmaceutical form for increasing CRY bioavailability represents an important requirement for exploiting its pharmacological potential. In the present study, the ability of soybean phosphatidylcholine (SPC) liposomes to improve bioavailability and absorption of CRY in cancer cells has been evaluated. Liposomal formulations of CRY, differing for lamellarity (i.e., unilamellar and multilamellar vesicles or ULV and MLV) and for the drug loading (i.e., 1:0.1, 1:0.3 and 1:0.5 mol/mol between SPC and CRY) were designed with the aim of maximizing CRY amount in the liposome bilayer, while avoiding its leakage during storage. The low-loaded formulations significantly potentiated the antiproliferative activity of CRY in both HepG2 and MDA-MB-468 cells, reaching a maximum IC50 lowering (from two to five folds) with 1:0.3 and 1:0.1 SPC/CRY MLV. Conversely, increasing liposome drug-loading reduced the ability for CRY release, likely due to a possible interaction between SPC and CRY that affects the membrane properties, as confirmed by physical measures.
引用
收藏
页数:17
相关论文
共 39 条
[1]  
Akopian David, 2015, Int J Biochem Res Rev, V5, P214
[2]  
Bangham A D, 1978, Ann N Y Acad Sci, V308, P2, DOI 10.1111/j.1749-6632.1978.tb22010.x
[3]   β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway [J].
Bento, Allisson Freire ;
Marcon, Rodrigo ;
Dutra, Rafael Cypriano ;
Claudino, Rafaela Franco ;
Cola, Maira ;
Pereira Leite, Daniela Ferraz ;
Calixto, Joao B. .
AMERICAN JOURNAL OF PATHOLOGY, 2011, 178 (03) :1153-1166
[4]  
Botre F., 2011, RECENT ADV DOPING AN, V19, P24
[5]   Protective Effect of β-Caryophyllene, a Natural Bicyclic Sesquiterpene, Against Cerebral Ischemic Injury [J].
Chang, Hyun-Joo ;
Kim, Ji-Myung ;
Lee, Jae-Chul ;
Kim, Won-Ki ;
Chun, Hyang Sook .
JOURNAL OF MEDICINAL FOOD, 2013, 16 (06) :471-480
[6]   Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes [J].
Coimbra, Maria ;
Isacchi, Benedetta ;
van Bloois, Louis ;
Torano, Javier Sastre ;
Ket, Aldo ;
Wu, Xiaojie ;
Broere, Femke ;
Metselaar, Josbert M. ;
Rijcken, Cristianne J. F. ;
Storm, Gert ;
Bilia, Rita ;
Schiffelers, Raymond M. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2011, 416 (02) :433-442
[7]   Microemulsions containing Copaifera multijuga Hayne oil-resin: Challenges to achieve an efficient system for β-caryophyllene delivery [J].
de Oliveira Neves, Jamilly Kelly ;
Apolinario, Alexsandra Conceicao ;
Alcantara Saraiva, Karina Lidiane ;
Casimiro da Silva, Dayanne Tomaz ;
de Freitas Araujo Reis, Mysrayn Yargo ;
Goulart de Lima Damasceno, Bolivar Ponciano ;
Pessoa, Adalberto, Jr. ;
Moraes Galvao, Marcos Aurelio ;
Lira Soares, Luiz Alberto ;
da Veiga Junior, Valdir Florencio ;
da Silva, Jose Alexsandro ;
Converti, Attilio .
INDUSTRIAL CROPS AND PRODUCTS, 2018, 111 :185-192
[8]   Caryophyllane sesquiterpenes inhibit DNA-damage by tobacco smoke in bacterial and mammalian cells [J].
Di Giacomo, Silvia ;
Abete, Lorena ;
Cocchiola, Rossana ;
Mazzanti, Gabriela ;
Eufemi, Margherita ;
Di Sotto, Antonella .
FOOD AND CHEMICAL TOXICOLOGY, 2018, 111 :393-404
[9]   Chemosensitizing Properties of β-Caryophyllene and β-Caryophyllene Oxide in Combination with Doxorubicin in Human Cancer Cells [J].
Di Giacomo, Silvia ;
Di Sotto, Antonella ;
Mazzanti, Gabriela ;
Wink, Michael .
ANTICANCER RESEARCH, 2017, 37 (03) :1191-1196
[10]   Mutagenicity of Cigarette Butt Waste in the Bacterial Reverse Mutation Assay: The Protective Effects of β-Caryophyllene and β-Caryophyllene Oxide [J].
Di Giacomo, Silvia ;
Mazzanti, Gabriela ;
Di Sotto, Antonella .
ENVIRONMENTAL TOXICOLOGY, 2016, 31 (11) :1319-1328