This study aimed to determine the effect of iontophoresis and chitosan gel on doxorubicin (DOX) skin penetration and cytotoxicity. Results showed that iontophoresis significantly increased DOX skin permeation and retention compared to passive delivery. While iontophoresis of hydroxyethylcellulose gel delivered more DOX to the stratum corneum, chitosan gel delivered similar amounts to deeper skin layers by competing for binding sites. Iontophoresis also increased DOX cytotoxicity against melanoma cells independently of the formulation used.

1. Effect of the iontophoresis of a chitosan gel on doxorubicin skin penetration and cytotoxicitySaketAsatiDept. of PharmaceuticsNIPERA1012PE12

2. Flow of seminarIntroductionResearch ArticleAimMaterials & MethodResult & DiscusionConclusionReferences

3. Human skin Most extensive and readily accessible organs of the human body.

4. It receives about 1/3 of the blood circulation through the body.

5. Adult body covers a surface area approximately 2m2

6. Average thickness of human skin: 0.5 mm.

7. The stratum corneum is effectively a 10-15μm thick.

8. The epidermis, is approximately 100 to150 µm thick.

9. Skin is a net negatively charged membrane under normal physiological condition.Skin structure

10. IontophoresisIontophoresis involves the application of a weak (low) electric current to the skin and allowing the drugs into the body, through the skin, by a potential gradient.Four components needed for effective Iontophoresis delivery:• Power source in order to generate controlled direct current.• Electrodes that contain the drug and disperse the drug.• Negatively or positively charged aqueous medication of small molecule size (nearly <8000 Daltons).• Treatment site (localized).

11. Mechanism involved In Iontophoresis, electrodes are present both anode and cathode. Anode represents a positively charged chamber whereas cathode represents a negatively charged chamber. Now the cationic drugs are kept under the anode or the anionic drugs are placed under the cathode.When a low voltage density current is applied, due to ‘Electro repulsion’, the ions will be repelled into the skin from the active electrode that is having the drug ions.

12. Cont….The amount of drug delivered is directly proportional to the quantity of electrical charge passed. Electromigration and electroosmosis are two different mechanisms contributing to the iontophoretic flux.In electromigration, the applied electrical potential gradient causes electrorepulsion between the positive electrode and a cationic drug.Electroosmosis causes a convective solvent flow in the anode-to cathode direction, which enhances the transport of cations and of neutral polar compounds, while diminishing the overall electrotransport of anions.

13. Cont….

14. Advantages over other drug delivery systems:When compared with injections: Free from pain and invasion.

15. Minimizes the needle-pricking accidents.

16. Allows the drug delivery by skin contact itself can be used outside hospitals.When compared to pills:Minimizes the on-set time

17. Adverse effects alleviation

18. Through this process, it is possible to delivery the drugs which dissolve and lose their potency and efficacy in the digestive organs.Cont….When compared to patches (adhesives):Shortens the on-set time

19. Drugs can de delivered quantitatively

20. Reduces the residual drug amount.

21. Chitosan gelChitosan is a linear polysaccharide composed of randomly distributed β-(1-4)-linked D-glucosamine and N-acetyl-D-glucosamine. The amino group in chitosan makes chitosan water soluble and cationic which readily binds to negatively charged surfaces such as mucosal membranes.Chitosan enhances the transport of polar drugs across epithelial surfaces, and is biocompatible and biodegradable.

22. Research article

23. AimTo determine the effect of iontophoresis on skin permeation & retension of doxorubicin (DOX).To determine the effect of chitosan gel on the electroosmotic flow.To determine the effect of low electric current on the melanoma cells.

24. MaterialsDoxorubicin hydrochloride (DOX)

25. Methanol

26. Tetrahydrofuran

27. Propylene glycol and ZnSO4

28. Natrosol 250 HHR hydroxyethylcellulose(HEC)

29. High molecular weight Chitosan (Hydagen® CMFP)

30. Deionized water

31. Pig ear skin

32. B16F10 Melanoma cellsPreparation of DOX formulationDOX 0.5% was dispersed in water, hydroxyethylcellulose (HEC) gel and chitosan gel.