Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinoma

Abstract

Transdermal delivery of drugs offers many advantages compared to traditional drug delivery systems, including oral and injectable preparations. Due to their amphiphilic nature, lipid vesicles may serve as non-toxic penetration enhancers for drugs (1, 2). However, this approach is not very successful because of poor skin permeability, breaking of vesicles, drug leakage, aggregation and fusion of vesicles. To overcome problems of poor skin permeability, a novel vesicular system, transfersomes (ultradeformable lipid vesicles) were proposed for non-invasive delivery of drugs into deep skin strata or across Cisplatin-loaded protransfersome system was prepared and characterized for in vitro drug permeation, drug deposition and antitumor effect. A histopathological study and a genotoxicity study were also done. The skin permeation data of cisplatin from protransfersome gel formulation revealed 494.33 ± 11.87 mg cm -2 , which was significantly higher than that from the control plain drug solution in 0.9 % NaCl (p < 0.001). Untreated group of animals showed invasive moderately differentiated keratinizing squamous cell carcinoma (malignant stage). However, with cisplatin loaded protransfersome gel system simple epithelial hyperplasia (pre-cancerous stage) with no cancerous growth was observed. Also, a significant induction in micronucleus formation was found in the group that was treated with injectable intraperitoneal cisplatin preparation in 0.9 % saline as compared to the group treated with topical protransfersome gel formulation. The findings of this research work appear to support improved, site-specific and localized drug action in the skin, thus providing a better option for dealing with skin related problems like squamous cell carcinoma.

Comparative study of curcumin and curcumin formulated in a solid dispersion: Evaluation of their antigenotoxic effects

“…cDDP was used as the damage-inducing agent in this study due its genotoxic and nephrotoxic effects, and the kidney was evaluated as a target organ. The genotoxic mechanisms of cDDP involve chromosomal damage, as demonstrated by the induction of micronuclei ( Gupta et al ., 2011 ); the formation of cDDP-DNA crosslinks, as shown by the decrease in the percentage of DNA in the tail ( Stang and Witte, 2009 ), and the regulation of Tp53 mRNA and p53 protein levels ( Yuan et al ., 2011 ). The in vivo mechanisms of cDDP nephrotoxicity are mainly related to the induction of oxidative stress: cDDP increases free radical production ( Ognjanovic et al ., 2012 ) and decreases antioxidant enzyme activity ( Badary et al ., 2005 ).…”

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“…After that, sections were stained with hematoxylin and eosin stain (H&E stain) and examined under a light microscope at ×40. [32,33] Histopathological examination of mice skin from control (Group I), carcinogen control (Group II), methotrexate geltreated (Group III), and methotrexate loaded emulsomal geltreated (Group IV) groups was performed after the 3 rd and 6 th weeks. It was found that the skin of the control group [Figure 6(1)] has thin epidermis and normal skin layers.…”

Topical Drug Delivery of Gossypin From Proniosomal Gel Formulations: In Vitro Efficacy Against Human Melanoma Cells

“…Localization of drugs improve long-term effectiveness [1]. This medicine is encapsulated in a vesicular medication supply to enhance the transdermal supply of liposomes, ethosomes, and transferosomes [17], but this medicinal substance may become unstable because of accumulation, hydrolysis, fusion and sedimentation during storage [18]. The delivery mechanisms of proniosomes solved vesicular system stability problems.…”