PMID- 24405470
OWN - NLM
STAT- MEDLINE
DCOM- 20150514
LR  - 20181202
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 11
IP  - 8
DP  - 2014 Aug 4
TI  - Doxorubicin and lapatinib combination nanomedicine for treating resistant breast 
      cancer.
PG  - 2600-11
LID - 10.1021/mp400687w [doi]
AB  - Our objective was to design a polymeric micelle-based doxorubicin and lapatinib 
      combination therapy for treating multidrug resistant (MDR) breast cancers. 
      Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonylpropylene carbonate) 
      (PEG-PBC) polymers were synthesized for preparing doxorubicin and lapatinib 
      loaded micelles using a film dispersion method. Micelles were characterized by 
      determining critical micelle concentration (CMC), particle size distribution, and 
      drug loading. The anticancer effects were determined in vitro with MTT assays as 
      well as with lactate dehydrogenase (LDH) release studies. In addition, the 
      cellular uptake of drug-loaded micelles was determined with fluorescence 
      microscopy and flow cytometry. Finally, in vivo anticancer activity and tolerance 
      of developed formulations were evaluated in resistant breast tumor bearing mice. 
      PEG5K-PBC7K polymer synthesized in this study had a low CMC value (1.5 mg/L) 
      indicating an excellent dynamic stability. PEG-PBC micelles could efficiently 
      load both doxorubicin and lapatinib drugs with a loading density of 21% and 8.4%, 
      respectively. The mean particle size of these micelles was 100 nm and was not 
      affected by drug loading. The use of lapatinib as an adjuvant sensitized drug 
      resistant MCF-7/ADR cells to doxorubicin treatment. Cellular uptake studies 
      showed enhanced doxorubicin accumulation in MCF-7/ADR cells in the presence of 
      lapatinib. The doxorubicin and lapatinib combination therapy showed a significant 
      decrease in tumor growth compared to doxorubicin monotherapy. In conclusion, we 
      have developed PEG-PBC micelle formulations for the delivery of doxorubicin and 
      lapatinib. The combination therapy of doxorubicin plus lapatinib has a great 
      potential for treating MDR breast cancer.
FAU - Wang, Huiyuan
AU  - Wang H
AD  - Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Hai-ke 
      Rd, Shanghai 201203, China.
FAU - Li, Feng
AU  - Li F
FAU - Du, Chengan
AU  - Du C
FAU - Wang, Huixin
AU  - Wang H
FAU - Mahato, Ram I
AU  - Mahato RI
FAU - Huang, Yongzhuo
AU  - Huang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140117
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Micelles)
RN  - 0 (Polypropylenes)
RN  - 0 (Quinazolines)
RN  - 0 (poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene 
      carbonate))
RN  - 0VUA21238F (Lapatinib)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 80168379AG (Doxorubicin)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/*drug therapy
MH  - Doxorubicin/*administration & dosage
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - L-Lactate Dehydrogenase/chemistry
MH  - Lapatinib
MH  - MCF-7 Cells
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Micelles
MH  - Microscopy, Fluorescence
MH  - Nanomedicine/*methods
MH  - Nanotechnology/methods
MH  - Neoplasm Transplantation
MH  - Particle Size
MH  - Polyethylene Glycols/chemistry
MH  - Polypropylenes/chemistry
MH  - Quinazolines/*administration & dosage/chemistry
EDAT- 2014/01/11 06:00
MHDA- 2015/05/15 06:00
CRDT- 2014/01/11 06:00
PHST- 2014/01/11 06:00 [entrez]
PHST- 2014/01/11 06:00 [pubmed]
PHST- 2015/05/15 06:00 [medline]
AID - 10.1021/mp400687w [doi]
PST - ppublish
SO  - Mol Pharm. 2014 Aug 4;11(8):2600-11. doi: 10.1021/mp400687w. Epub 2014 Jan 17.