PMID- 25543531
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20151119
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 16
IP  - 2
DP  - 2015 Feb 9
TI  - Injectable biodegradable hydrogels from vitamin D-functionalized polycarbonates 
      for the delivery of avastin with enhanced therapeutic efficiency against 
      metastatic colorectal cancer.
PG  - 465-75
LID - 10.1021/bm5015206 [doi]
AB  - Humanized vascular endothelial growth factor (VEGF) antibody (bevacizumab; 
      Avastin) is a highly effective monoclonal antibody against metastatic colorectal 
      cancer and several other advanced late stage cancers. However, limited aqueous 
      solubility and short circulation half-life of the antibody result in long 
      infusion time (30-90 min) and frequent injections. Such direful medical 
      procedures often cause considerable patient inconvenience and prolonged pharmacy 
      preparation. Subcutaneous delivery of Avastin using injectable hydrogels can 
      continuously provide Avastin to treat the malignancy and mitigate antibody 
      degradation. In this study, ABA triblock copolymers of vitamin D-functionalized 
      polycarbonate and poly(ethylene glycol), that is, VDm-PEG-VDm were synthesized 
      and employed to form physically cross-linked injectable hydrogels for 
      encapsulation and subcutaneous delivery of Avastin in a sustained fashion. 
      Antitumor studies were performed using two different HCT116 xenograft mouse 
      models: a subcutaneous and an intraperitoneal metastatic tumor models. The 
      therapeutic efficacy of Avastin-loaded hydrogel injected subcutaneously (s.c.) 
      was compared to an Avastin solution injected via either intravenous (i.v.) or 
      intraperitoneal (i.p.) route. In the subcutaneous tumor model, the Avastin-loaded 
      hydrogel resulted in greater tumor suppression as compared to i.v. and i.p. 
      administration of Avastin solution. The biodistribution pattern of the hydrogel 
      delivery system was also different from the other formulations as there was 
      significantly higher accumulation in the tumor tissue and lesser accumulation 
      within the liver and kidneys as compared to Avastin delivered through i.v. and 
      i.p. administration. Furthermore, in vivo studies carried out on mice with 
      peritoneal metastasis demonstrated that Avastin-loaded hydrogel and weekly 
      administration of Avastin solution resulted in higher survival (87 and 77% over 
      62 days, respectively) when compared to the control, blank hydrogel and bolus 
      Avastin solution (i.v.; 50-60%). The antimetastatic activity of Avastin delivered 
      using a one-time injection of the hydrogel was as effective as that of 4x weekly 
      injections (i.v.) of Avastin. The reduced injection frequency provided by the 
      subcutaneous formulation may enhance patient convenience and compliance for 
      metastatic cancer therapy.
FAU - Lee, Ashlynn L Z
AU  - Lee AL
AD  - Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 
      Singapore 138669, Singapore.
FAU - Ng, Victor W L
AU  - Ng VW
FAU - Gao, Shujun
AU  - Gao S
FAU - Hedrick, James L
AU  - Hedrick JL
FAU - Yang, Yi Yan
AU  - Yang YY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150116
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biocompatible Materials)
RN  - 0 (Hydrogels)
RN  - 0 (Polycarboxylate Cement)
RN  - 1406-16-2 (Vitamin D)
RN  - 25766-59-0 (polycarbonate)
RN  - 2S9ZZM9Q9V (Bevacizumab)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/*metabolism
MH  - Bevacizumab
MH  - Biocompatible Materials/administration & dosage/metabolism
MH  - Colorectal Neoplasms/drug therapy/*metabolism
MH  - Drug Delivery Systems/*methods
MH  - Female
MH  - HCT116 Cells
MH  - HEK293 Cells
MH  - Humans
MH  - Hydrogels/administration & dosage/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Polycarboxylate Cement/*metabolism
MH  - Treatment Outcome
MH  - Vitamin D/administration & dosage/*metabolism
MH  - Xenograft Model Antitumor Assays/methods
EDAT- 2014/12/30 06:00
MHDA- 2015/10/27 06:00
CRDT- 2014/12/30 06:00
PHST- 2014/12/30 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
AID - 10.1021/bm5015206 [doi]
PST - ppublish
SO  - Biomacromolecules. 2015 Feb 9;16(2):465-75. doi: 10.1021/bm5015206. Epub 2015 Jan 
      16.