Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 270
  • Home
  • Print this page
  • Email this page
Cover page of the Journal of Health Sciences


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 13  |  Issue : 3  |  Page : 230-234

Effect of tamoxifen-loaded transdermal patch on physical and biochemical parameters in DMBA-induced breast cancer


1 Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
2 Department of Pharmaceutics, KLE College of Pharmacy, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India

Date of Submission08-Feb-2020
Date of Acceptance13-Jul-2020
Date of Web Publication05-Oct-2020

Correspondence Address:
Ms. Anjana Adhyapak
Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi - 590 010, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_38_20

Rights and Permissions
  Abstract 

Background: The current study assessed the effect of tamoxifen-loaded transdermal patch in Dimethylbenz(a)anthracene (DMBA)-induced breast cancer.
Materials and Methods: Different formulations composed of various concentrations of tamoxifen citrate, poly (SA: RA), glucose, mannitol were formulated and were evaluated in DMBAinduced breast cancer in female albino Wistar rats. Multiple parameters such as body weight, hemoglobin content, red blood cell, white blood cell, SGPT, and SGOT were evaluated.
Results: Treatment with formulations showed a decrease in body weight contrast to disease. Equally, a considerable increase in hemoglobin was observed in the formulation treated group over disease grouping. Likewise, there decrease in SGPT and SGOT in formulation compared to disease.
Conclusion: The present study revealed a transdermal patch loaded with tamoxifen showed promising antitumor activity.

Keywords: Anticancer, nanoformulation, tamoxifen, transdermal patch


How to cite this article:
Adhyapak A, Desai B G. Effect of tamoxifen-loaded transdermal patch on physical and biochemical parameters in DMBA-induced breast cancer. Indian J Health Sci Biomed Res 2020;13:230-4

How to cite this URL:
Adhyapak A, Desai B G. Effect of tamoxifen-loaded transdermal patch on physical and biochemical parameters in DMBA-induced breast cancer. Indian J Health Sci Biomed Res [serial online] 2020 [cited 2020 Oct 24];13:230-4. Available from: https://www.ijournalhs.org/text.asp?2020/13/3/230/297196


  Introduction Top


Patients with carcinoma are prescribed with tamoxifen for prophylactic care in pre- and postmenopausal females.[1] It is a triphenylethylene derivative (nonsteroidal) and competes with steroids for steroid receptor positive in carcinoma cells. However, this agent is associated with multiple side effects such as multifocal viscous, fatty infiltration, hepatotoxicity, viscous sphacelus, and blood disorders.[2],[3]

Formulation loaded with tamoxifen in the transdermal patch would possess lower hepatotoxicity and hemolytic carcinoma possessing higher patient adherence to treatment. This system plays an important role in promoting pharmacokinetic profile, enhancing efficacy, followed by minimization of toxicity [4] which could be the outcome of minimal particle size possessing them to penetrate biological barriers.[5],[6] Nanoparticles can be helpful as controlled release system, applied for cancer medical care and decrease the exploding of multiple side effects. Hence, the present study aimed to investigate the tamoxifen-loaded transdermal patch against breast carcinoma. Formulations were composed of a drug (tamoxifen), polymer (poly (SA:RA), and cryoprotectant (glucose and mannitol) at multiple concentrations. The detail of multiple formulations is summarized in [Table 1].
Table 1: Composition of formulations

Click here to view



  Materials and Methods Top


Evaluation of in vivo antitumor property

The study was performed after performing acute toxicity as OECD 423[7] A mixture containing 25 mg of DMBA was dissolved in 1 ml of a vehicle and injected by subcutaneous route. Tumor yield was evaluated after the end of the study. Seven different which composed 12 female albino rats in each group were used. Each group comprised of 12 female albino rats.

  1. Group 1: The normal control
  2. Group 2: The cancer group negative control
  3. Group 3: The tamoxifen group positive control (PC)
  4. Group 4: F-1
  5. Group 5: F-2
  6. Group 6: F-3
  7. Group 7: F-4.


Test sample treatment

Tamoxifen was injected i. p. for PC. Normal group was injected with vehicle. Similarly, Groups 4, 5, 6, and 7 were treated with multiple formulations, and the study was carried for 30 days. At the end of the study, multiple physical and biochemical parameters were evaluated.

Parameters evaluated

Body weight was measured at the end of the study, and each group was compared to evaluate the role of formulation in tumor treatment. Similarly, hematological parameters such as hemoglobin, white blood cell (WBC), and red blood cell (RBC) counts were also determined in peripheral blood. Further, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were also quantified using commercially available kits. Institutional ethics approval was obtained from the institutional ethics committee Ref. No KLECOP/CPCSEA-Reg No 221/Res-13-2010.


  Results Top


Effect on final body weight

In the disease group, there was a considerable increase in body weight compared to a normal group. Similarly, in the PC group, there was a considerable decrease in body weight compared to the cancer group. Similarly, formulation F1 showed a considerable decrease in body weight compared to the cancer group. Likewise, formulation F2 showed a considerable decrease in body weight compared to the cancer group. Further, the F3 group showed a considerable decrease compared to the cancer group. Similarly, the F4 group showed a considerable decrease compared to the cancer group [Figure 1].
Figure 1: Effect of multiple formulations in body weight ***P < 0.001 compared to normal control, #P < 0.05, ##P < 0.01, ###P < 0.001 compared to cancer group

Click here to view


Effect on hemoglobin content

The hemoglobin content in the disease group was found to be considerably decreased in the disease group compared to normal control. Similarly, there was a considerable increase in hemoglobin content in the PC compared to the disease group. Similarly, formulations F1, F3, and F4 also showed a considerable increase in hemoglobin content compared to the normal disease group. However, formulation F2 did not affect hemoglobin content compared to the disease group [Figure 2].
Figure 2: Effect of formulations on hemoglobin content (gm/dl) ***P < 0.001 compared to normal group, ##P < 0.01 compared to disease control group

Click here to view


Effect on red blood cell count

RBC count was considerably decreased in the disease group compared to a normal group and was increased in the PC compared to the disease group. There was an increase in RBC count in formulation treatments. However, the results were not considerable [Figure 3].
Figure 3: Effect of formulations in red blood cell ***P < 0.001 compared to normal, ###P < 0.001 compared to disease group

Click here to view


Effect on white blood cell count

There was a considerable decrease in WBC count in the disease group compared to the normal group. Similarly, there was a considerable increase in WBC count in PC compared to the disease group. There was an increase in WBC count in formulation treated groups; however, the results were not considerably different compared to the disease control group [Figure 4].
Figure 4: Effect of formulations in white blood cell ***P < 0.001 compared to normal, ###P < 0.001 compared to disease group

Click here to view


Effect on tumor weight

The PC group showed a considerable decrease in tumor weight in the PC group compared to the disease group. Likewise, treating with formulations F1 and F2 showed an equal level of a considerable decrease in tumor weight compared to disease control. Likewise, formulation F3 showed a considerable decrease in tumor weight compared to the disease group. However, formulation F4 had no effect in decreasing tumor weight compared to the disease group [Figure 5].
Figure 5: Effect of formulations in tumor weight *P < 0.05, **P < 0.01, ***P < 0.001 compared to disease group

Click here to view


Effect on SGPT

A considerable increase in the SGPT level was found in the disease group compared to normal. However, there was a considerable decrease in the SGPT level in tamoxifen and formulation (F1–F4)-treated groups. Furthermore, there was a decreased level in the SGPT level in formulations compared to the tamoxifen group [Figure 6].
Figure 6: Effect on SGPT levels ***P < 0.001 compared to normal group, ###P < 0.001 compared to disease group

Click here to view


Effect on SGOT level

SGOT level in the disease group was found to be considerably higher compared to normal. However, there was a considerable decrease in the SGOT level in tamoxifen and formulation (F1–F4)-treated groups. Furthermore, there was a decreased level in the SGOT level in formulations compared to the tamoxifen group [Figure 7].
Figure 7: Effect on SGOT levels ***P < 0.001 compared to normal group, ###P < 0.001 compared to disease group

Click here to view



  Discussion Top


In the present study, we investigated four different formulations and were assessed for multiple parameters including body weight, tumor weight, RBC, WBC, and hemoglobin content. All the results were also compared with the gold standard treatment procedure for tamoxifen.

Nanoformulations are well-accepted formulations in the pharmacotherapy of multiple diseases including breast cancer.[8] Further, breast cancer includes a polygenic risk for the development of its pathogenesis.[9] It is more convenient in the pharmacotherapy of such polygenic conditions since the treating is quite easy and the drug release is fast through this approach. The present study also showed a decrease in tumor weight by formulations F1, F2, and F3. Likewise, there was a decrease in body weight in the formulation-treated group. This represents that the formations have the capacity to release the tamoxifen in the targeted site.

Furthermore, cancer is a polygenic condition.[10] The pharmacotherapy of this condition could be complicated, though we target a specific molecule or protein. On the other hand, a single compound can modulate multiple proteins and regulate multiple pathways.[11] Although the tamoxifen-loaded formulation has been studied in the present study, there is always a probability that it could modulate multiple proteins and pathways as previously predicted,[12],[13],[14],[15] which needs to be still applied for tamoxifen-loaded formulations.

Previous literature suggests that there is a decrease in hemoglobin in cancer pathogenesis,[16] which has been revealed by the formulation treated in the present study. Further, there was an increase in RBC and WBC, but the results were not considerable compared to the disease group. This reflects that the sympathomimetic relief has not been achieved within the lowered time which could be achieved after long-term treatment and is the scope of future study.

One of the major limitations in the pharmacotherapy of cancer is increased SGOT and SGPT levels reflecting the hepatotoxicity,[17] which needs to be minimized. In our study, there was a decrease in the SGOT and SGPT levels after tamoxifen treatment. Further, our formulation showed a decreased level of SGOT and SGPT compared to the tamoxifen group, which could be the outcome of targeted drug delivery.


  Conclusion Top


The present study demonstrated the anticancer activity of multiple formulations and their effectiveness in multiple biochemical and hematological parameters reflecting the importance of nanoparticles in cancer pharmacotherapy and targeted drug delivery system.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Heery M, Corbett P, Zelkowitz R. Precautions for patients taking tamoxifen. J Adv Pract Oncol 2018;9:78-83.  Back to cited text no. 1
    
2.
Maximov PY, Lee TM, Jordan VC. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol 2013;8:135-55.  Back to cited text no. 2
    
3.
Yang G, Nowsheen S, Aziz K, Georgakilas AG. Toxicity and adverse effects of tamoxifen and other anti-estrogen drugs. Pharmacol Ther 2013;139:392-404.  Back to cited text no. 3
    
4.
Gunasekaran T, Haile T, Nigusse T, Dhanaraju MD. Nanotechnology: An effective tool for enhancing bioavailability and bioactivity of phytomedicine. Asian Pac J Trop Biomed 2014;4:S1-7.  Back to cited text no. 4
    
5.
Zhang XQ, Xu X, Bertrand N, Pridgen E, Swami A, Farokhzad OC. Interactions of nanomaterials and biological systems: Implications to personalized nanomedicine. Adv Drug Deliv Rev 2012;64:1363-84.  Back to cited text no. 5
    
6.
De Jong WH, Borm PJ. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 2008;3:133-49.  Back to cited text no. 6
    
7.
OECD Guideline for Testing of Chemicals. Acute Oral Toxicity– Acute Toxic Class Method. Available from: https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecd_gl423.pdf. [Last accessd on 18 June 2019].  Back to cited text no. 7
    
8.
Yezhelyev MV, Gao X, Xing Y, Al-Hajj A, Nie S, O'Regan RM. Emerging use of nanoparticles in diagnosis and treatment of breast cancer. Lancet Oncol 2006;7:657-67.  Back to cited text no. 8
    
9.
Mina LA, Arun B. Polygenic risk scores in breast cancer. Curr Breast Cancer Rep 2019;11:117.  Back to cited text no. 9
    
10.
Bredberg A. Cancer: More of polygenic disease and less of multiple mutations? A quantitative viewpoint. Cancer 2011;117:440-5.  Back to cited text no. 10
    
11.
Khanal P, Patil BM, Mandar BK, Dey YN, Duyu T. Network pharmacology-based assessment to elucidate the molecular mechanism of anti-diabetic action of Tinospora cordifolia. Clin Phytosci 2019;5:35.  Back to cited text no. 11
    
12.
Khanal P, Patil BM. Gene set enrichment analysis of alpha-glucosidase inhibitors from Ficus benghalensis. Asian Pac J Trop Biomed 2019;9263-70.  Back to cited text no. 12
    
13.
Khanal P, Mandar BK, Patil BM, Hullatti KK. In silico antidiabetic screening of Borapetoside C, Cordifolioside A and Magnoflorine. Indian J Pharm Sci 2019;81:550-5.  Back to cited text no. 13
    
14.
Khanal P, Mandar BK, Magadum P, Patil BM, Hullatti KK. In silico docking study of limonoids from Azadirachta indica with pfpk5: A novel target for Plasmodium falciparum. Indian J Pharm Sci 2019;81:326-32.  Back to cited text no. 14
    
15.
Patil VS, Biradar PR, Attar V, Khanal P. In silico docking analysis of active biomolecules from Cissus quadrangularis L. against PPAR-γ. Indian J Pharm Educ 2019;53:S332-7.  Back to cited text no. 15
    
16.
Dicato M, Plawny L, Diederich M. Anemia in cancer. Ann Oncol 2010;21 Suppl 7:vii167-72.  Back to cited text no. 16
    
17.
Singh TD, Barbhuiya MA, Poojary S, Shrivastav BR, Tiwari PK. The liver function test enzymes and glucose level are positively correlated in gallbladder cancer: A cancer registry data analysis from North central India. Indian J Cancer 2012;49:125-36.  Back to cited text no. 17
[PUBMED]  [Full text]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
   Materials and Me...
  Results
  Discussion
  Conclusion
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed43    
    Printed0    
    Emailed0    
    PDF Downloaded6    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]