Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy in vitro.
OBJECTIVE
With the purpose of delivering high doses of glabrescione B (GlaB) to solid tumors after systemic administration, long-circulating GlaB-loaded oil-cored polymeric nanocapsules (NC-GlaB) were formulated.


METHODS
Synthesis of GlaB and its encapsulation in nanocapsules (NCs) was performed. Empty and GlaB-loaded NCs were assessed for their physico-chemical properties, in vitro cytotoxicity and in vivo biodistribution.


RESULTS
GlaB was efficiently loaded into NCs (∽90%), which were small (∽160 nm), homogeneous and stable upon storage. Further, GlaB and NC-GlaB demonstrated specific activities against the cancer stem cells. Preliminary studies in tumor-bearing mice supported the ability of NC to accumulate in pancreatic tumors.


CONCLUSIONS
This study provides early evidence that NC-GlaB has the potential to be utilized in a preclinical setting and justifies the need to perform therapeutic experiments in mice.
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.|Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Rome, Italy.
Cinzia
C
Ingallina
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Pedro M
PM
Costa
Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
Francesca
F
Ghirga
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Rebecca
R
Klippstein
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Julie T
JT
Wang
Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Rome, Italy.|Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
Simone
S
Berardozzi
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Naomi
N
Hodgins
Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
Paola
P
Infante
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh bioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK.
Steven M
SM
Pollard
Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Rome, Italy.
Bruno
B
Botta
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Khuloud T
KT
Al-Jamal
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D002867:Chromones / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D053769:Nanocapsules / Q000737:chemistry*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D002867:Chromones; D004337:Drug Carriers; D053823:Hedgehog Proteins; D053769:Nanocapsules; C000613265:glabrescione B; D011092:Polyethylene Glycols
Hedgehog (Hh) pathway; glabrescione B (GlaB); oil-cored polymeric nanocapsules