TY - JOUR
T1 - New long-acting injectable microspheres prepared by IVL-DrugFluidic™ system
T2 - 1-month and 3-month in vivo drug delivery of leuprolide
AU - Kim, Minsung
AU - Kim, Ju Hee
AU - Kim, Seyeon
AU - Maharjan, Ravi
AU - Kim, Nam Ah
AU - Jeong, Seong Hoon
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/6/25
Y1 - 2022/6/25
N2 - The microspheres for 1-month (PLGA-based) and 3-month (PLA-based) drug releases of leuprolide were manufactured using an IVL-DrugFluidic™ system and their morphology, particle size and distribution, and encapsulation efficiency were compared with the commercialized products. In vivo test was also conducted to monitor the amount of leuprolide and testosterone in plasma after a single subcutaneous injection in male Sprague–Dawley (SD) rats and male Beagle dogs. The median diameter, span value, drug loading, and encapsulation efficiency of PLGA-based microspheres (63.29 μm, 0.26, 13.15%, and 78.90%, respectively) and PLA-based microspheres (80.28 μm, 0.21, 14.42%, and 86.50%, respectively) demonstrated narrow particle size distribution (monodispersed) and efficient drug loading/encapsulation efficiency. Both the microspheres exhibited a desired time-dependent drug release profile and reduced initial burst release by 16-fold in SD rats and 240-fold in Beagle dogs compared to Leuplin DPS®. Moreover, the testosterone level in plasma was suppressed to < 0.50 ng/mL after 28 days with a steady plasma drug concentration. The results suggested that newly developed leuprolide-loaded microspheres produced by the IVL-DrugFluidic™ system could provide extended drug release with advantages such as reduced initial burst release and testosterone level suppression, along with steady plasma drug concentration, over the existing products.
AB - The microspheres for 1-month (PLGA-based) and 3-month (PLA-based) drug releases of leuprolide were manufactured using an IVL-DrugFluidic™ system and their morphology, particle size and distribution, and encapsulation efficiency were compared with the commercialized products. In vivo test was also conducted to monitor the amount of leuprolide and testosterone in plasma after a single subcutaneous injection in male Sprague–Dawley (SD) rats and male Beagle dogs. The median diameter, span value, drug loading, and encapsulation efficiency of PLGA-based microspheres (63.29 μm, 0.26, 13.15%, and 78.90%, respectively) and PLA-based microspheres (80.28 μm, 0.21, 14.42%, and 86.50%, respectively) demonstrated narrow particle size distribution (monodispersed) and efficient drug loading/encapsulation efficiency. Both the microspheres exhibited a desired time-dependent drug release profile and reduced initial burst release by 16-fold in SD rats and 240-fold in Beagle dogs compared to Leuplin DPS®. Moreover, the testosterone level in plasma was suppressed to < 0.50 ng/mL after 28 days with a steady plasma drug concentration. The results suggested that newly developed leuprolide-loaded microspheres produced by the IVL-DrugFluidic™ system could provide extended drug release with advantages such as reduced initial burst release and testosterone level suppression, along with steady plasma drug concentration, over the existing products.
KW - Drug-delivery system
KW - IVL-DrugFluidic™
KW - Initial burst release
KW - Leuprolide
KW - Long-acting injectables
UR - http://www.scopus.com/inward/record.url?scp=85131646111&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2022.121875
DO - 10.1016/j.ijpharm.2022.121875
M3 - Article
C2 - 35636628
AN - SCOPUS:85131646111
SN - 0378-5173
VL - 622
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 121875
ER -