PMID- 31071977
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231012
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 11
IP  - 5
DP  - 2019 May 8
TI  - Systemic Design and Evaluation of Ticagrelor-Loaded Nanostructured Lipid Carriers 
      for Enhancing Bioavailability and Antiplatelet Activity.
LID - 10.3390/pharmaceutics11050222 [doi]
LID - 222
AB  - Ticagrelor (TGL), a P2Y(12) receptor antagonist, is classified as 
      biopharmaceutics classification system (BCS) class IV drug due to its poor 
      solubility and permeability, resulting in low oral bioavailability. 
      Nanostructured lipid carriers (NLC) are an efficient delivery system for the 
      improvement of bioavailability of BCS class IV drugs. Hence, we prepared 
      TGL-loaded NLC (TGL-NLC) to enhance the oral bioavailability and antiplatelet 
      activity of TGL with a systemic design approach. The optimized TGL-NLC with 
      Box-Behnken design showed a small particle size of 87.6 nm and high encapsulation 
      efficiency of 92.1%. Scanning electron microscope (SEM), differential scanning 
      calorimetry (DSC), and powder X-ray diffraction (PXRD) were performed to 
      investigate the characteristics of TGL-NLC. Furthermore, TGL-NLC exhibited 
      biocompatible cytotoxicity against Caco-2 cells. Cellular uptake of TGL-NLC was 
      1.56-fold higher than that of raw TGL on Caco-2 cells. In pharmacokinetic study, 
      the oral bioavailability of TGL-NLC was 254.99% higher than that of raw TGL. In 
      addition, pharmacodynamic study demonstrated that the antiplatelet activity of 
      TGL-NLC was superior to that of raw TGL, based on enhanced bioavailability of 
      TGL-NLC. These results suggest that TGL-NLC can be applied for efficient oral 
      absorption and antiplatelet activity of TGL.
FAU - Son, Gi-Ho
AU  - Son GH
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      kyk2576@naver.com.
AD  - Present affiliation: Korea United Pharmaceutical Co. Ltd., 25-23, 
      Nojangongdan-gil. Jeondong-myeon, Sejong 30011, Korea. kyk2576@naver.com.
FAU - Na, Young-Guk
AU  - Na YG
AUID- ORCID: 0000-0002-7937-1626
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      youngguk@cnu.ac.kr.
FAU - Huh, Hyun Wook
AU  - Huh HW
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      hhw3573@nate.com.
FAU - Wang, Miao
AU  - Wang M
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      wmclare@163.com.
FAU - Kim, Min-Ki
AU  - Kim MK
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      zkzkang@naver.com.
FAU - Han, Min-Gu
AU  - Han MG
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      linuxfalcon@naver.com.
FAU - Byeon, Jin-Ju
AU  - Byeon JJ
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      jinju.byeon.cnu@gmail.com.
FAU - Lee, Hong-Ki
AU  - Lee HK
AUID- ORCID: 0000-0003-3670-386X
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      dvmlhk@gmail.com.
FAU - Cho, Cheong-Weon
AU  - Cho CW
AUID- ORCID: 0000-0001-8390-0132
AD  - College of Pharmacy and Institute of Drug Research and Development, Chungnam 
      National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea. 
      chocw@cnu.ac.kr.
LA  - eng
GR  - 2016R1A2B4011294/National Research Foundation of Korea (NRF) funded by the 
      Ministry of Education, Science and Technology/
PT  - Journal Article
DEP - 20190508
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC6572397
OTO - NOTNLM
OT  - Box-Behnken design
OT  - antiplatelet activity
OT  - bioavailability
OT  - design of experiments
OT  - nanostructured lipid carrier
OT  - ticagrelor
COIS- The authors declare no conflict of interest. Gi-Ho Son is employees of Korea 
      United Pharmaceutical Co. Ltd. The company had no role in the design of the 
      study; in the collection, analyses, or interpretation of data; in the writing of 
      the manuscript, and in the decision to publish the results.
EDAT- 2019/05/11 06:00
MHDA- 2019/05/11 06:01
PMCR- 2019/05/01
CRDT- 2019/05/11 06:00
PHST- 2019/04/15 00:00 [received]
PHST- 2019/05/03 00:00 [revised]
PHST- 2019/05/06 00:00 [accepted]
PHST- 2019/05/11 06:00 [entrez]
PHST- 2019/05/11 06:00 [pubmed]
PHST- 2019/05/11 06:01 [medline]
PHST- 2019/05/01 00:00 [pmc-release]
AID - pharmaceutics11050222 [pii]
AID - pharmaceutics-11-00222 [pii]
AID - 10.3390/pharmaceutics11050222 [doi]
PST - epublish
SO  - Pharmaceutics. 2019 May 8;11(5):222. doi: 10.3390/pharmaceutics11050222.