Initial Leuprolide Acetate Release from Poly(D,L-lactide-co-glycolide) in Situ Forming Implants as Studied by Ultraviolet-Visible Imaging
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Initial Leuprolide Acetate Release from Poly(D,L-lactide-co-glycolide) in Situ Forming Implants as Studied by Ultraviolet-Visible Imaging. / Li, Zhuoxuan; Mu, Huiling; Larsen, Susan Weng; Jensen, Henrik; Ostergaard, Jesper.
In: Molecular Pharmaceutics, Vol. 17, No. 12, 2020, p. 4522-4532.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Initial Leuprolide Acetate Release from Poly(D,L-lactide-co-glycolide) in Situ Forming Implants as Studied by Ultraviolet-Visible Imaging
AU - Li, Zhuoxuan
AU - Mu, Huiling
AU - Larsen, Susan Weng
AU - Jensen, Henrik
AU - Ostergaard, Jesper
PY - 2020
Y1 - 2020
N2 - The initial drug release from in situ forming implants is affected by factors such as the physicochemical properties of the active pharmaceutical ingredient, the type of the excipients utilized, and the surrounding environment. The feasibility of UV-vis imaging for characterization of the initial behavior of poly(Dplactide-co-glycolide) (PLGA)/1-methyl-2-pyrrolidinone (NMP) in situ forming implants was investigated. The in vitro release of leuprolide acetate (LA) and implant formation in real time were monitored using dual-wavelength imaging at 280 and 525 nm, respectively, in matrices based on agarose gel and hyaluronic acid (HA) solution emulating the subcutaneous matrix. Three hours upon injection of the pre-formulation, approximately 15% of the total amount of LA administered was found in the agarose gel, while 5% was released from the implant into the HA solution. Concurrently, more extensive swelling of the implants in the HA solution as compared to implants in the agarose gel was observed. Transport of both LA and the solvent NMP was investigated using UV-vis imaging in a small-scale cell where the geometry of the formulation was controlled, showing a linear correlation between drug release and solvent escape. Light microscopy showed that the microstructures of the resulting implants in agarose gel and HA solution were different, which may be attributed to the different solvent exchange rates. UV imaging was also used to examine the interaction of LA with the release medium by characterizing the diffusion of LA in agarose gel, HA solution, and phosphate buffered saline. The reduced LA diffusivity in HA solution as compared to agarose gel and the LA distribution coefficient in the agarose gel-HA system indicated the presence of interactions between LA and HA Our findings show that the external environment affects the solvent exchange kinetics for in situ forming implants in vitro, resulting in different types of initial release behavior. UV-vis imaging in combination with biorelevant matrices may offer an interesting approach in the development of in situ forming implant delivery systems.
AB - The initial drug release from in situ forming implants is affected by factors such as the physicochemical properties of the active pharmaceutical ingredient, the type of the excipients utilized, and the surrounding environment. The feasibility of UV-vis imaging for characterization of the initial behavior of poly(Dplactide-co-glycolide) (PLGA)/1-methyl-2-pyrrolidinone (NMP) in situ forming implants was investigated. The in vitro release of leuprolide acetate (LA) and implant formation in real time were monitored using dual-wavelength imaging at 280 and 525 nm, respectively, in matrices based on agarose gel and hyaluronic acid (HA) solution emulating the subcutaneous matrix. Three hours upon injection of the pre-formulation, approximately 15% of the total amount of LA administered was found in the agarose gel, while 5% was released from the implant into the HA solution. Concurrently, more extensive swelling of the implants in the HA solution as compared to implants in the agarose gel was observed. Transport of both LA and the solvent NMP was investigated using UV-vis imaging in a small-scale cell where the geometry of the formulation was controlled, showing a linear correlation between drug release and solvent escape. Light microscopy showed that the microstructures of the resulting implants in agarose gel and HA solution were different, which may be attributed to the different solvent exchange rates. UV imaging was also used to examine the interaction of LA with the release medium by characterizing the diffusion of LA in agarose gel, HA solution, and phosphate buffered saline. The reduced LA diffusivity in HA solution as compared to agarose gel and the LA distribution coefficient in the agarose gel-HA system indicated the presence of interactions between LA and HA Our findings show that the external environment affects the solvent exchange kinetics for in situ forming implants in vitro, resulting in different types of initial release behavior. UV-vis imaging in combination with biorelevant matrices may offer an interesting approach in the development of in situ forming implant delivery systems.
KW - biorelevant matrix
KW - injectable
KW - in situ forming implant
KW - in vitro release
KW - PLGA
KW - UV-vis imaging
KW - HYDROGEL MATRIX MIMICKING
KW - PHASE INVERSION DYNAMICS
KW - VITRO RELEASE
KW - DRUG-RELEASE
KW - VIVO PERFORMANCE
KW - DIFFUSION
KW - DELIVERY
KW - SYSTEM
KW - LACTIDE
KW - MODEL
U2 - 10.1021/acs.molpharmaceut.0c00625
DO - 10.1021/acs.molpharmaceut.0c00625
M3 - Journal article
C2 - 33164519
VL - 17
SP - 4522
EP - 4532
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 12
ER -
ID: 255735882