Title:Papain Loaded Solid Lipid Nanoparticles for Colorectal Cancer Therapy
VOLUME: 14 ISSUE: 1
Author(s):Suriyakala P. Chandran, Kannika P. Nachinmuthu, Satheesh B. Natarajan*, Mohammad G. Inamdar and Masliza S.B.M. Shahimi
Affiliation:Department of Biochemistry, Dr. N.G.P. Arts and Science College, Coimbatore, Department of Biochemistry, Dr. N.G.P. Arts and Science College, Coimbatore, Department of Pharmaceutics, Faculty of Pharmacy, Lincoln University College, 15050 Kota Bharu, Kelantan, Department of Pharmaceutics, Faculty of Pharmacy, Lincoln University College, 15050 Kota Bharu, Kelantan, Department of Pharmaceutics, Faculty of Pharmacy, Lincoln University College, 15050 Kota Bharu, Kelantan
Keywords:Papain, cytotoxic potential, solid lipid nanoparticles, cell viability, proteolytic enzyme,
Colorectal cancer (CRC).
Abstract:Background: Colorectal cancer (CRC) also known as bowl cancer is still one of the
leading causes of cancer related mortality worldwide. Generally tumor cells are protecting themselves
by fibrin coat and it is resistant to fibrinolytic degradation. Such a coated tumor appears as
‘self' to the immune system, and thus is not detected as a tumor by the immune system (i.e. natural
killer cells). Hence, a potent proteolytic enzyme has to propose/ identify to dissolve the protective
fibrin layer, exposing the tumor cell surface to chemotherapy and immune attack. In this research
papain was considered to be the potential proteolytic agent, can break down the fibrin coat
of cancer cell wall and ultimately the cancer cells are exposed to immune attack and help against
the cancer. Secondly, the cytotoxic compound(s) directly deliver to cancer site without harm to
normal cells.
Methods: The attempt made to attain this objective, we were designed to fabricate the Papain
loaded solid lipid nanoparticles (SLN) by melt dispersion-ultrasonication technique, and investigate
the various formulation parameters. The papain loaded SLN was characterized by particle
size analysis, zeta potential analysis, differential scanning calorimetry (DSC), Scanning electron
microscopy (SEM), drug encapsulation efficiency, in vitro drug release, and in vitro cytotoxicity
studies on HT-29 colorectal cancer cells.
Results: The successful outcome of this research was that, the cetyl alcohol based SLN of papain
were successfully prepared by using melt dispersion- ultrasonication method with maximum encapsulation
efficiency with desired particle size. The release profile of the produced SLN was investigated
in phosphate buffer media, and it showed prolonged release during 24 h. The drug release
behaviour from the SLNs exhibited a biphasic pattern with the burst release at the initial
stage and sustained release subsequently. Future perspective of this research is that need to investigate
the SLN for the lymphatic uptake to produce local action on metastatic colorectal cancer. In
vitro cell viability for P-SLNs was tested on colorectal Adenocarcinoma HT-29 cells by MTT assay.
The results revealed that the in vitro cell viability against different concentrations of papain
was 99% and 31 % which were treated with 5µg/ml and 80µg/ml concentration respectively. The
cell viability of HT-29 cells was decreased signicantly from 94 % to 17 % treated with P-SLN at 5
µg/ml and 80 µg/ml concentration respectively. Therefore, the papain loaded SLNs exhibits a better
performance on getting lower cell viability (or) equivalent high cytotoxicity than that of pure
papain. Therefore, the SLNs delivery system plays a significant role in enhancing the cytotoxic
efficacy of papain enzyme against colorectal cancer cells.
Conclusion: In this research, we successfully formulated the P-SLN for the treatment of colorectal
cancer therapy. We investigate the various formulation parameters, drug release profile and cytotoxic
efficacy of P-SLN. Upon successful completion of this work, P-SLNs delivery system is
predictable to produce enhanced cytotoxic efficacy against HT-29 colorectal cancer cells. The papain
loaded SLNs can potentially be utilized as a drug delivery system for the treatment of colorectal
cancer. In future, we will explore further to investigate the mechanism of anticancer activity
and clinical investigation of P-SLN.
