Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug
Authors: Subrata Majumdar
Abhinav Agarwal
Govind P Agrawal
Narendra Lariya
Ashay Jain
Himanshu Agrawal
Anil Khaya
Saikat Majumder
Journal: Journal of Controlled Release (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: tumor targeting potential; solid lipid nanoparticles; doxorubicin HCl; mannosylation; drug release
Affiliations: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, MP 470003, India.

Abstract:  The purpose of the present study was to investigate the tumor targeting potential of surface tailored solid lipid nanoparticles (SLNs) loaded with an anti-cancer drug doxorubicin HCl (DOX). DOX encapsulating SLNs were prepared, characterized and further mannosylated. The developed formulations were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), particle size/polydispersity index and zeta-potential analysis. The formulations were evaluated for in vitro drug release and hemolytic toxicity. The ex vivo cytotoxicity and cellular uptake studies were performed on A549 cell lines. In vivo studies were conducted to determine pharmacokinetics, tissue distribution pattern and nephrotoxic/hepatotoxic effect of mannosylated SLNs. In vitro, the formulations exhibited a biphasic pattern characterized by initial rapid release of the drug followed by rather slow and prolonged release. Further, the in vitro studies depicted mannose-conjugated SLNs to be least hemolytic and suitable for sustained drug delivery. Mannosylated SLNs were most cytotoxic and were preferably taken up A549 tumor cells as evaluated against uncoated SLNs and plain DOX. Pharmacokinetic studies revealed improved bioavailability, half life and mean residence time of DOX upon mannose conjugation. The biodistribution pattern exhibited that mannosylated SLNs were able to deliver a higher concentration of DOX in the tumor mass. They were also proficient to circumvent damage to renal as well as hepatic tissues. It may therefore be interpreted that mannosylated SLNs are capable to ferry bioactives selectively and specifically to the tumor sites with the interception of minimal side effects, thereby suggesting their potential application in cancer chemotherapy. 

Retracted: No

PubPeer comments:
  Fig. 1. TEM photomicrographs of ... (b) mannosylated SLNs.  Reviewers and editors looked at this exercise in Matisse-style *decoupage* and thought  Yes, that s exactly what a TEM image should look like. , 
 Yes there is a mistake! Thank you for pointing out. , 
 #2 Perhaps either you or I misunderstand the nature of the concern. I believe Hoya is illustrating the fact that features may have been copied and pasted to create this image. This suggests to me that readers and the peer reviewers have been misled. How do you see this image as u201ca mistake?u201d It would also be appreciated if you could respond to the other 5 papers posted here which have similar concerns: https: pubpeer.com search?q=Himanshu+Agrawal+ , 
 #3 I am also curious about the repeating T motif visible in the background of Fig 1B at increased contrast. Is it a watermark?  Areas of background are surprisingly similar in 1A and 1B, notably around the corners, but that may be a repeated artefact in the TEM for all I know. ,