Online ISSN: 2515-8260

Volume 3, Issue 1

Volume 3, Issue 1, Winter 2016


Chemotherapeutic effect of 3, 3′-Diindolylmethane encapsulated chitosan nanoparticles on 7, 12-Dimethylbenz (a) anthracene induced mammary cancer – A dose dependent study

Stainsloss Isabella; Sankaran Mirunalini

European Journal of Molecular & Clinical Medicine, 2016, Volume 3, Issue 1, Pages 1-8

Breast cancer is the second most prevalent cancer among women and its incidence is amplifying alarmingly. Since genetic factors are believed to account for only 10% of the reported cases, remaining the environmental factors, including diet are thought to play a significant role in predisposing breast cancer. Many bioactive compounds have been reported for their anticancer potential. One among the bioactive compound 3, 3′-Diindolylmethane (DIM) is a phytochemical possess a wide array of pharmacological activities such as anti-proliferative and anti-oxidant properties. Its properties such as poor water solubility and low bioavailability have hampered its clinical development. Therefore, it is a great interest to study whether the nano formulation for DIM with chitosan for its enhanced potential, the present study was aimed to evaluate the chemotherapeutic potential of 3, 3′- Diindolylmethane encapsulated chitosan nanoparticles (DIM@CS-NP) on 7,12-Dimethylbenz(a)anthracene (DMBA) induced mammary carcinoma in rats. DMBA was induced in a single subcutaneous injection of 25 mg/ kg body weight to each rat. In the present study, we investigated the altered activities of lipid peroxidation, enzymatic antioxidants (SOD, CAT, GPx) and non- enzymatic antioxidant (GSH) in plasma, liver and mammary tissue, supported by histopathological study of mammary tissues. We evaluated the changes in the body weight of control and experimental animals. There was a significant decrease in the final body weight of tumor bearing animals, when compared to control animals. Also, we observed a diminished cellular antioxidant status and the elevated oxidant levels in plasma, liver, mammary tissues of DMBA induced rats. However, administration of DIM@CS-NP significantly increased the mean final body weight when compared with DMBA induced animals. Oral supplementation of different doses of DIM@CS-NP (0.5, 1, 2 mg/kg BW), significantly renovated the activities of cellular antioxidants and ultimately diminished the levels of lipid peroxidation, which pointed towards suppression of preneoplastic lesions, thereby reduced the cancer risk, and significant improvement in the levels of enzymatic (SOD, CAT, GPx) and non- enzymatic antioxidant (GSH) in the plasma, liver and mammary tissue. Based on the above finding we conclude the nano formulation of DIM provides a novel therapeutic regime for mammary cancer.

Translational aspects in targeting the stromal tumour microenvironment: From bench to bedside

R. Bhome; H.A. Al Saihati; R.W. Goh; M.D. Bullock; J.N. Primrose; G.J. Thomas; A.E. Sayan; A.H. Mirnezami

European Journal of Molecular & Clinical Medicine, 2016, Volume 3, Issue 1, Pages 9-21

Solid tumours comprise, not only malignant cells but also a variety of stromal cells and extracellular matrix proteins. These components interact via an array of signalling pathways to create an adaptable network that may act to promote or suppress cancer progression. To date, the majority of anti-tumour chemotherapeutic agents have principally sought to target the cancer cell. Consequently, resistance develops because of clonal evolution, as a result of selection pressure during tumour expansion. The concept of activating or inhibiting other cell types within the tumour microenvironment is relatively novel and has the advantage of targeting cells which are genetically stable and less likely to develop resistance. This review outlines key players in the stromal tumour microenvironment and discusses potential targeting strategies that may offer therapeutic benefit. Focal points: Benchside J The tumour stroma consists of mesenchymal, immune and vascular cells housed in an extracellular matrix. Stromal cells and extracellular matrix proteins represent genetically stable targets which can be exploited in cancer treatment. Numerous in vitro and animal studies support the concept of stromal-directed treatment. Bedside J Several therapeutic strategies have been developed or repurposed to target the stroma. The antiangiogenic agent bevacizumab was one of the first specific stromal-targeting agents to be licensed for cancer treatment over a decade ago. More recently, immune modulation of the stroma has become a hugely successful strategy, with novel drugs such as checkpoint inhibitors set to revolutionise cancer treatment. Governments J Funding bodies should continue to acknowledge the pivotal role that the stroma plays in cancer progression, in parallel with cancer cell itself. Undoubtedly, the most successful treatment regimens of the future will address both the “seed” and the “soil”. & 2016 The Authors. Published by Elsevier Ltd. on behalf of European Society for Translational Medicine. This is an open access article under the CC BY license

Development and characterization of chitosan-based antimicrobial films incorporated with streptomycin loaded starch nanoparticles

Neethu Hari; Ananthakrishnan Jayakumaran Nair

European Journal of Molecular & Clinical Medicine, 2016, Volume 3, Issue 1, Pages 22-29

Nowadays, Chitosan has attained more attention due to its potential applications in food, agriculture and pharmaceutics. The cationic nature of chitosan enhances the film forming capacity of this polymer. However, films made only from chitosan lack water resistance and have reduced mechanical properties. The functional properties of chitosan films can be improved when chitosan films are combined with other film forming materials. The objective of this study was to prepare chitosan based antimicrobial films by the incorporation of streptomycin loaded starch Nanocrystals. Different properties of this film such as swelling nature, moisture content, degradation nature and the antimicrobial activity of modified chitosan films were investigated. Drug releasing efficacy of the film was also studied. The addition of streptomycin loaded Starch nanocrystals in chitosan-gelatin film increased crystallinity of the film, lowered the swelling nature of the film to a controlled manner. Moreover the Modified chitosan based antimicrobial film showed almost 90% of Escherichia coli inhibition and 80% of Bacillus subtilis inhibition and also the film showed a sustained release (60%) of streptomycin for 10 days. Focal point: Benchside Synthesis of streptomycin loaded starch nanoparticles (SS-NPs) using nanoprecipitation method and the development of novel chitosan based antimicrobial film by the incorporation of streptomycin loaded starch nanoparticles using solvent casting technique Bedside Development of potential multifunctional antimicrobial film for medical, pharmaceutical and food based applications due to its excellent film forming ability, biocompatibility, biodegradability and antimicrobial property Industry The designed unique antimicrobial film, if finely tuned, can be used both in biomedical fields for developing scaffolds in tissue engineering, wound dressing material, capsule material for sustained drug release and immobilization of enzyme and food industry as packaging material Government Financial investment and support from government would help to develop new novel translational tools which contribute for better health care and also help to reduces disease burden Regulatory Stringent regulatory principles limit the clinical trials essential for validation of biomaterials which might have turned in to a highly beneficial multifunctional product such as antimicrobial film potentially useful both in biomedical and food industry

Scientific Abstracts presented at the 5th International Convention of Association of Pharmacy Professionals: Redesigning Pharmacy Education and Regulations for Translational Drug Research in India, hosted at Anna University, Centre for Excellence in Nanobio Translational Research, Bharathidasan Institute of Technology Campus, Tiruchirappalli, Tamil Nadu, India, 22nd–23rd January, 2016.

Selvamani Palanisamy; Latha Subbiah; Ruckmani Kandasamy

European Journal of Molecular & Clinical Medicine, 2016, Volume 3, Issue 1, Pages 30-61

Globally, breast cancer is the second most prevalent cancer among women and its incidence is amplifying alarmingly. Since genetic factors is believed to account for only 10% of the reported cases, remaining the environmental factors including diet are thought to play a significant role in predisposing breast cancer. Many bioactive compounds have been reported for their anticancer potential. One among the bioactive compound is 3,30 - diindolylmethane (DIM) is a phytochemical possess a wide array of pharmacological activities such as anti-proliferative and antioxidant properties. Its properties such as poor water solubility and low bioavailability have hampered its clinical development. Therefore, it is a great interest to study whether the nano formulation for DIM with chitosan for an enhanced their potential, the present study was aimed to evaluate the chemotherapeutic potential of 3,30 -diindolylmethane (DIM) encapsulated chitosan nanoparticles (DIM@CS-NP) on 7,12-dimetheyl benz(a)anthracene (DMBA) induced mammary carcinoma in female Sprague Dawley rats. Methods: DMBA was induced in a single subcutaneous injection of 25 mg/kg body weight to each rat. In the present study, we investigated altered the activities of lipid peroxidation, enzymatic antioxidants (SOD, CAT, GPx) and non- enzymatic antioxidant (GSH) in plasma, liver and mammary tissue, supported by histopathological study of mammary tissues. Results: We evaluated the changes in the body weight of control and experimental animals. There was an significant decreased in the final body weight of tumor bearing animals, when compared to control animals. However, administration of DIM@CS-NP significantly increased the mean final body weight when compared with DMBA induced animals. Further, there was an diminished cellular antioxidant status and the elevated oxidant levels in plasma, liver, mammary tissues of DMBA induced rats. Whereas, after oral supplementation with different dose of DIM@CS-NP, DIM@CS-NP 0.5 mg/kg BW significantly renovated the activities of cellular antioxidants and ultimately diminished the level of lipid peroxidation which point towards suppression of preneoplastic lesions thereby reduced the cancerous risk, and significant improvement in the levels of enzymatic (SOD, CAT, GPx) and non- enzymatic antioxidant (GSH) in the plasma, liver and mammary tissue