Annonaceous acetogenins nanosuspensions stabilized by poloxamer 188: Preparation, properties and in vivo evaluation

Author(s):  
Jianwei Han ◽  
Xinxin Zhou ◽  
Jingxin Fu ◽  
Guangyu Gao ◽  
Cuiling Zuo ◽  
...  
Author(s):  
Ajith J. George ◽  
Bibu J. Kariyil ◽  
Usha P.T. Ayyappan ◽  
Anu Gopalakrishnan

Background: Triple negative breast cancers (TNBCs) are having high morbidity and shorter survival rate in the population. These types of cancers are having high aggressiveness, lymphatic invasion and absence of receptors. The treatment options for these types of cancers are also scarce. Several studies have been conducted to investigate the effectiveness of seeds of Annona muricata for its anti cancer activities in various cancer cell lines such as lung A549, breast MCF7, colon HT-29, oral KB and human hepatoma cell lines. But works related to its anticancer effect and mechanism of action in TNBCs has not been elucidated. Objective: The present study was undertaken to evaluate the in vitro, in vivo and in silico anticancer potential of chloroform fraction of methanolic extract of seeds of Annona muricata (CMAM) against TNBC along with elucidation of its mechanistic pathway. Methods: In vitro cytotoxicity- and antiproliferative- studies in three triple negative breast cancer cell lines were conducted using MTT and SRB assays respectively. The mechanism through which CMAM exerts its pharmacological effect was elucidated in vitro employing cell morphological assessment studies using acridine orange/ ethidium bromide (AO/EB), intra cellular reactive oxygen species assay, DNA fragmentation assay, agarose gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cell cycle analysis, annexin binding assay and caspase activated mitochondria mediated apoptotic assays using western blot. In vivo evaluation in 4T1 induced murine mammary tumour model was also conducted. Phytoconstituents in CMAM was analysed using liquid chromatography mass spectroscopy. In silico binding studies with various annonaceous acetogenins against BCL-2 and cyclin E were performed. Results: Cytotoxicity studies in MDA-MD-231, 4TI and BT-549 revealed the IC50 value of CMAM to be 2.5±0.14, 4.8±0.3 and 4.5±0.16 µg/mL respectively. Anti proliferative studies in 4T1, MDA-MB-231 and BT-549 revealed the GI50 values to be 0.128+0.03, 18.03+0.20, 0.95+0.04 µg/mL respectively. CMAM exhibited its cytotoxicity through the lysis of cell membrane, ROS dependent caspase activated mitochondria mediated apoptosis, and arresting the S phase of the cell cycle. In vivo evaluation also supported the tumoricidal property of CMAM as evidenced by reduction in tumour volume and serum biomarkers. Histopathologically there was a marked reduction in cellularity, nuclear chromatin condensation and a few normal cells in group treated with CMAM at a dose of 31mg/Kg. Phytoconstituent evaluation has revealed the presence of annonaceous acetogenins in CMAM. Among the various annonaceous acetogenins, muricatacin alone showed lipophilicity and binding affinity towards BCL-2 and cyclin E1. Conclusion: The current study shows the effectiveness of CMAM against TNBC both in vitro and in vivo. This anticancerous effect of CMAM could be by virtue of its ROS dependent caspase activated mitochondria mediated apoptosis and the S-phase arrest of the cell cycle in the TNBCs. Our results indicate that the presence of annonaceous acetogenins, especially muricatacin, could be contributing to this anticanceros effect of CMAM. Thus muricatacin could be a potential candidate for the targeted therapy of TNBCs.


2007 ◽  
Vol 343 (1-2) ◽  
pp. 228-237 ◽  
Author(s):  
M NEWA ◽  
K BHANDARI ◽  
D LI ◽  
T KWON ◽  
J KIM ◽  
...  

2020 ◽  
Vol 20 (1) ◽  
pp. 76-87
Author(s):  
S.A. Chime ◽  
A.A. Attama ◽  
G.C. Onunkwo

Background: Stavudine is an antiretroviral therapy with so many side effects and has a short half-life of 1.5 h. It degrades to thymine under hydrolytic, oxidative and photolytic conditions hence has major formulation challenges. Objectives: To formulate sustained release lipid based stavudine and to study the properties of the formulations by in vitro and in vivo methods. Methods: Stavudine tablets were formulated by moulding using validated tablets moulds. The carrier used were solidified reverse micellar solution (SRMS) made up of varying ratios of hydrogenated palm oil and Phospholipid admixtures. Evaluation tests were carried out on the tablets using both Pharmacopoeial and non Pharmacopoeial test. Drug release was studied in both simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). In vivo release was studied using Wistar rats. Results: The results showed that stavudine tablets exhibited weight range of 372 ± 0.14 to 386 ± 0.52 mg, friability ranged from 0.00 to 0.13 % and hardness ranged from 4.27 ± 0.25 to 5.30 ± 0.21 Kgf. Tablets formulated with SRMS 1:2 had erosion time range of 60.80 ± 1.23 to 87.90 ± 2.33 min and was affected significantly by the presence of Poloxamer 188 (p < 0.05). The formulations exhibited T100 % at 10 to13 h in SIF. Stavudine tablets showed the area under the curve (AUC) of 854.0 μg/h/ml, significantly higher than the AUC of the reference (p < 0.05). Conclusion: Stavudine SRMS-based tablets had good stability and sustained release properties. Formulations containing 1 % Poloxamer 188 exhibited enhanced in vivo absorption and hence could be used once daily in order to enhance the bioavailability of this drug..


2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S598-S598 ◽  
Author(s):  
Laurent Martarello ◽  
Vincent J Cunningham ◽  
Julian C Matthews ◽  
Eugenii Rabiner ◽  
Steen Jakobsen ◽  
...  

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S595-S595 ◽  
Author(s):  
Wynne K Schiffer ◽  
Deborah Pareto-Onghena ◽  
HaiTao Wu ◽  
Kuo-Shyan Lin ◽  
Andrew R Gibbs ◽  
...  

Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  

2008 ◽  
Vol 56 (S 1) ◽  
Author(s):  
D Ruzicka ◽  
W Eichinger ◽  
I Hettich ◽  
S Bleiziffer ◽  
R Guenzinger ◽  
...  
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