Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles: implications on oral bioavailability, antitumor efficacy, and drug-induced toxicity
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Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles : implications on oral bioavailability, antitumor efficacy, and drug-induced toxicity. / Jain, Amit K; Thanki, Kaushik; Jain, Sanyog.
In: Molecular Pharmaceutics, Vol. 10, No. 9, 03.09.2013, p. 3459-74.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles
T2 - implications on oral bioavailability, antitumor efficacy, and drug-induced toxicity
AU - Jain, Amit K
AU - Thanki, Kaushik
AU - Jain, Sanyog
PY - 2013/9/3
Y1 - 2013/9/3
N2 - The present investigation reports the preparation, optimization, and characterization of orally administrable PLGA-NPs co-encapsulated with tamoxifen (Tmx) and quercetin (QT). The developed formulation was found to have particle size 185.3 ± 1.20 nm, PDI 0.184 ± 0.004, entrapment efficiency 67.16 ± 1.24% Tmx, 68.60 ± 1.58% QT at a Tmx/QT ratio of 1:2 w/w. The stability of the freeze-dried formulation was established in simulated gastrointestinal fluids for 8 h and at accelerated stability condition for 3 months. DPPH free radical scavenging assay confirmed that the functional architecture of QT was retained in freeze-dried NPs. Higher cellular uptake, cytotoxicity, and nuclear co-localization of Tmx-QT-NPs in MCF-7 cells revealed higher efficiency of the formulation. At the same time, higher Caco-2 cell uptake revealed its potential for oral delivery, which was well corroborated with in vivo pharmacokinetics, which suggested ∼ 5-fold and ∼ 3-fold increase in oral bioavailability as compared to the free Tmx citrate and free QT, respectively. Concomitantly, significantly higher tumor suppression was observed in the case of the developed formulation in contrast to respective free drug(s) and their combination when tested against a DMBA-induced breast cancer model in female SD rats. Multiple oral administrations of Tmx-QT-NPs efficiently controlled the tumor angiogenesis as revealed by normalized levels of respective markers (MMP-2 and MMP-9). The safety profile of Tmx-QT-NPs was also established, and no measurable hepatotoxicity or oxidative stress was observed when measured as a function of respective biochemical markers in contrast to free drug(s) and their combinations. In a nutshell, the co-encapsulation strategy with PLGA-NPs could be a promising approach in improving oral delivery of Tmx and QT for cancer therapy.
AB - The present investigation reports the preparation, optimization, and characterization of orally administrable PLGA-NPs co-encapsulated with tamoxifen (Tmx) and quercetin (QT). The developed formulation was found to have particle size 185.3 ± 1.20 nm, PDI 0.184 ± 0.004, entrapment efficiency 67.16 ± 1.24% Tmx, 68.60 ± 1.58% QT at a Tmx/QT ratio of 1:2 w/w. The stability of the freeze-dried formulation was established in simulated gastrointestinal fluids for 8 h and at accelerated stability condition for 3 months. DPPH free radical scavenging assay confirmed that the functional architecture of QT was retained in freeze-dried NPs. Higher cellular uptake, cytotoxicity, and nuclear co-localization of Tmx-QT-NPs in MCF-7 cells revealed higher efficiency of the formulation. At the same time, higher Caco-2 cell uptake revealed its potential for oral delivery, which was well corroborated with in vivo pharmacokinetics, which suggested ∼ 5-fold and ∼ 3-fold increase in oral bioavailability as compared to the free Tmx citrate and free QT, respectively. Concomitantly, significantly higher tumor suppression was observed in the case of the developed formulation in contrast to respective free drug(s) and their combination when tested against a DMBA-induced breast cancer model in female SD rats. Multiple oral administrations of Tmx-QT-NPs efficiently controlled the tumor angiogenesis as revealed by normalized levels of respective markers (MMP-2 and MMP-9). The safety profile of Tmx-QT-NPs was also established, and no measurable hepatotoxicity or oxidative stress was observed when measured as a function of respective biochemical markers in contrast to free drug(s) and their combinations. In a nutshell, the co-encapsulation strategy with PLGA-NPs could be a promising approach in improving oral delivery of Tmx and QT for cancer therapy.
KW - Administration, Oral
KW - Animals
KW - Antineoplastic Agents, Hormonal
KW - Breast Neoplasms
KW - Caco-2 Cells
KW - Female
KW - Humans
KW - Lactic Acid
KW - Nanoparticles
KW - Oxidative Stress
KW - Polyglycolic Acid
KW - Polymers
KW - Quercetin
KW - Rats
KW - Rats, Sprague-Dawley
KW - Tamoxifen
U2 - 10.1021/mp400311j
DO - 10.1021/mp400311j
M3 - Journal article
C2 - 23927416
VL - 10
SP - 3459
EP - 3474
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 9
ER -
ID: 161995333