Anti-cancer activity of bromelain nanoparticles by oral administration
Authors: Priyanka Bhatnagar
Amulya K Panda
Kailash C Gupta
Amit K Srivastava
Mohan K R Mudiam
Pradeep Kumar
Aditya B Pant
Yogeshwer Shukla
Soma Patnaik
Journal: Journal of Biomedical Nanotechnology (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Oral administration; anti-cancer drugs; Bromelain; Poly(lactic-co-glycolic acid) (PLGA); nanoparticles

Abstract:  Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy. 

Retracted: No

PubPeer comments:
 Figs 2C, 5C. ![file] The blue box marks a panel that matches a panel in Figs 2C, 5C, 6C of [Jiao, Liu Tian (2019)] . The match is not perfect, but all the points in the present version seem to exist in the latter version (along with additional points). It is as if they emerged from the same raw-data file, differently filtered or gated. ![file] Here in context: ![file] , 
 *[right* Fig 7B.  Representative images of [H522] tumor xenografts in the agomir-718 group and agomir-NC group . *[left]* Fig 7B from [Cheng et al (2020)] .  A representative image of the [Sw1990] tumors at the end of the experiment . ![file] Different institutions from different provinces, but curiously they appear to be using the same ruler (white fleck just to the left of cm ). UPDATE: Another sighting of 7B! Fig 7A from [Xu et al (2020)] .  Representative images of subcutaneous xenografts derived from the agomir-936- or agomir-NC-transfected Y79 cells . ![] , 
 Retracted [21 July 2021] . ---------------------------------------------- Following the publication of this paper, the authors have contacted the Editorial Office to explain that they are unable to reproduce the results of their experiments designed to show the regulatory actions of miRu2011718 on the proliferation of nonu2011small cell lung cancer, and consequently they wish to retract the paper. The Editor of *International Jounal of Molecular Medicine* has granted their request that the paper be retracted. All the authors agree to this retraction. The Editor and the authors apologize to the readership for any inconvenience caused. ,