Abstract
In order to improve water solubility of a lipophilic drug, tacrolimus (FK506), two prodrugs (FK506-G or FK506-S) such as FK506-M32-LS-G (FK506-G) and FK506-M32-LS-SL (FK506-S) were synthesized. Two prodrugs (FK506-G or FK506-S), including FK506, were characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), enzymatic kinetics, and cytotoxicity. A phase solubility test was conducted in distilled water, and the solubility of two prodrugs (FK506-G or FK506-S) was measured in various pH values for pH solubility profiles. Most interesting was that FK506-S showed the highest solubility, 866 μg/mL in water. In vitro enzymatic kinetics of two prodrugs (FK506-G or FK506-S) in human plasma was evaluated by measuring the decrease of FK506-G or FK506-S as well as the increase of FK506 by HPLC, and FK506-G or FK506-S was metabolized in 1 h in human plasma. Two prodrugs (FK506-G or FK506-S) including FK506 showed an IC50 of 336.6 μg/mL for FK506, 337.9 μg/mL for FK506-G, or 480.1 μg/mL for FK506-S against a conjunctive cell line, Clone 1-5c-4 cells. Taken together, FK506-S could be the most optimal prodrug for aqueous preparations based on preformulation data.
| Original language | English |
|---|---|
| Pages (from-to) | 1313-1319 |
| Number of pages | 7 |
| Journal | Bulletin of the Korean Chemical Society |
| Volume | 37 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2016 Aug 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Chemistry(all)
Cite this
}
Preformulation of FK506 prodrugs for improving solubility. / Na, Young Guk; Jun, Hye Suk; Kim, Daehee; Park, Byong Chul; Lim, Si Kyu; Lee, Ki Ho; Hwang, Sung Joo; Park, Jeong Sook; Jung, Sang Hun; Cho, Cheong Weon.
In: Bulletin of the Korean Chemical Society, Vol. 37, No. 8, 01.08.2016, p. 1313-1319.Research output: Contribution to journal › Article
TY - JOUR
T1 - Preformulation of FK506 prodrugs for improving solubility
AU - Na, Young Guk
AU - Jun, Hye Suk
AU - Kim, Daehee
AU - Park, Byong Chul
AU - Lim, Si Kyu
AU - Lee, Ki Ho
AU - Hwang, Sung Joo
AU - Park, Jeong Sook
AU - Jung, Sang Hun
AU - Cho, Cheong Weon
PY - 2016/8/1
Y1 - 2016/8/1
N2 - In order to improve water solubility of a lipophilic drug, tacrolimus (FK506), two prodrugs (FK506-G or FK506-S) such as FK506-M32-LS-G (FK506-G) and FK506-M32-LS-SL (FK506-S) were synthesized. Two prodrugs (FK506-G or FK506-S), including FK506, were characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), enzymatic kinetics, and cytotoxicity. A phase solubility test was conducted in distilled water, and the solubility of two prodrugs (FK506-G or FK506-S) was measured in various pH values for pH solubility profiles. Most interesting was that FK506-S showed the highest solubility, 866 μg/mL in water. In vitro enzymatic kinetics of two prodrugs (FK506-G or FK506-S) in human plasma was evaluated by measuring the decrease of FK506-G or FK506-S as well as the increase of FK506 by HPLC, and FK506-G or FK506-S was metabolized in 1 h in human plasma. Two prodrugs (FK506-G or FK506-S) including FK506 showed an IC50 of 336.6 μg/mL for FK506, 337.9 μg/mL for FK506-G, or 480.1 μg/mL for FK506-S against a conjunctive cell line, Clone 1-5c-4 cells. Taken together, FK506-S could be the most optimal prodrug for aqueous preparations based on preformulation data.
AB - In order to improve water solubility of a lipophilic drug, tacrolimus (FK506), two prodrugs (FK506-G or FK506-S) such as FK506-M32-LS-G (FK506-G) and FK506-M32-LS-SL (FK506-S) were synthesized. Two prodrugs (FK506-G or FK506-S), including FK506, were characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), enzymatic kinetics, and cytotoxicity. A phase solubility test was conducted in distilled water, and the solubility of two prodrugs (FK506-G or FK506-S) was measured in various pH values for pH solubility profiles. Most interesting was that FK506-S showed the highest solubility, 866 μg/mL in water. In vitro enzymatic kinetics of two prodrugs (FK506-G or FK506-S) in human plasma was evaluated by measuring the decrease of FK506-G or FK506-S as well as the increase of FK506 by HPLC, and FK506-G or FK506-S was metabolized in 1 h in human plasma. Two prodrugs (FK506-G or FK506-S) including FK506 showed an IC50 of 336.6 μg/mL for FK506, 337.9 μg/mL for FK506-G, or 480.1 μg/mL for FK506-S against a conjunctive cell line, Clone 1-5c-4 cells. Taken together, FK506-S could be the most optimal prodrug for aqueous preparations based on preformulation data.
UR - http://www.scopus.com/inward/record.url?scp=84979503401&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979503401&partnerID=8YFLogxK
U2 - 10.1002/bkcs.10861
DO - 10.1002/bkcs.10861
M3 - Article
AN - SCOPUS:84979503401
VL - 37
SP - 1313
EP - 1319
JO - Bulletin of the Korean Chemical Society
JF - Bulletin of the Korean Chemical Society
SN - 0253-2964
IS - 8
ER -