TY - JOUR
T1 - Selective anti-ErbB3 aptamer modified sorafenib microparticles
T2 - In vitro and in vivo toxicity assessment
AU - Ali, Muhammad Yasir
AU - Tariq, Imran
AU - Farhan Sohail, Muhammad
AU - Amin, Muhammad Umair
AU - Ali, Sajid
AU - Pinnapireddy, Shashank Reddy
AU - Ali, Asad
AU - Schäfer, Jens
AU - Bakowsky, Udo
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/12
Y1 - 2019/12
N2 - The delivery of aptamer modified therapeutic moieties to specific tissue sites has become one of the major therapeutic choices to reduce the toxicity of inhibitory drugs. Bearing this in mind, the current study was designed using sorafenib (SFB) encapsulated microparticles (MP) prepared with biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) copolymer. The surfaces of these microparticles were modified with RNA aptamer having a binding affinity towards ErbB3 receptors. SFB-loaded MP (MPS) were prepared by o/w solvent evaporation method and the surface was coupled with the amino group of aptamer by EDC/NHS chemistry. Physiochemical investigations were done by dynamic light scattering, scanning electron microscopy and FTIR. In vitro apoptosis assay, cell viability assay and metastatic progression showed a significant decrease (p < 0.001) in vitro cell viability for MPS and MPS-Apt as compared to MP. The synergistic combination of SFB and aptamer also decreased the metastatic progression of cells for an extended period. Microparticles were also evaluated for in vivo toxicity in female BALB/c mice. It was evident that the presence of aptamer decreased the generalized toxicity of MPS-Apt, as measured by mean body weight loss and blood profiles, keeping all the blood formed elements level within acceptable limits. The histopathological investigations showed some necrotic and pyknotic bodies. In a similar fashion, liver function test and renal function tests showed pronounced effects of formulations on vital organs.
AB - The delivery of aptamer modified therapeutic moieties to specific tissue sites has become one of the major therapeutic choices to reduce the toxicity of inhibitory drugs. Bearing this in mind, the current study was designed using sorafenib (SFB) encapsulated microparticles (MP) prepared with biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) copolymer. The surfaces of these microparticles were modified with RNA aptamer having a binding affinity towards ErbB3 receptors. SFB-loaded MP (MPS) were prepared by o/w solvent evaporation method and the surface was coupled with the amino group of aptamer by EDC/NHS chemistry. Physiochemical investigations were done by dynamic light scattering, scanning electron microscopy and FTIR. In vitro apoptosis assay, cell viability assay and metastatic progression showed a significant decrease (p < 0.001) in vitro cell viability for MPS and MPS-Apt as compared to MP. The synergistic combination of SFB and aptamer also decreased the metastatic progression of cells for an extended period. Microparticles were also evaluated for in vivo toxicity in female BALB/c mice. It was evident that the presence of aptamer decreased the generalized toxicity of MPS-Apt, as measured by mean body weight loss and blood profiles, keeping all the blood formed elements level within acceptable limits. The histopathological investigations showed some necrotic and pyknotic bodies. In a similar fashion, liver function test and renal function tests showed pronounced effects of formulations on vital organs.
KW - CLSM
KW - Cancer
KW - PLGA
KW - Polymer
KW - SEM
UR - http://www.scopus.com/inward/record.url?scp=85073947993&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2019.10.003
DO - 10.1016/j.ejpb.2019.10.003
M3 - Article
C2 - 31626948
AN - SCOPUS:85073947993
SN - 0939-6411
VL - 145
SP - 42
EP - 53
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -
