Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme.
Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ(9)-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain.
Dolores
D
Hernán Pérez de la Ossa
Mar
M
Lorente
Maria Esther
ME
Gil-Alegre
Sofía
S
Torres
Elena
E
García-Taboada
María Del Rosario
Mdel R
Aberturas
Jesús
J
Molpeceres
Guillermo
G
Velasco
Ana Isabel
AI
Torres-Suárez
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002185:Cannabidiol / Q000008:administration & dosage*; D002188:Cannabis / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D013759:Dronabinol / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D011108:Polymers / Q000008:administration & dosage; D014183:Transplantation, Heterologous
D011108:Polymers; D002185:Cannabidiol; D013759:Dronabinol