Topotecan-loaded lipid nanoparticles as a viable tool for the topical treatment of skin cancers.

Abstract

OBJECTIVES:

This work aimed to evaluate semisolid formulations containing topotecan (TPT) loaded nanostructured lipid carriers (NLC) for topical treatment of skin cancers, as TPT is effective against a variety of tumours. A formulation which increases TPT skin permeation would be extremely desirable.

METHODS:

TPT-NLC were prepared and incorporated in hydrogels with hydroxyethyl cellulose and chitosan (TPT-NLC-HEC and TPT-NLC-Ch, respectively). Control formulations were obtained by dispersing TPT in HEC and Ch hydrogels (TPT-HEC and TPT-Ch).

KEY FINDINGS:

TPT-NLC-HEC and TPT-NLC-Ch showed to maintain the drug and nanoparticle dispersions stable for up to 30 days. When nanoparticles were incorporated into gels, TPT release was significantly decreased (P < 0.05). Still, TPT-NLC-HEC increased 2.37 times permeation compared with TPT-HEC (11.9 and 5.0 μg/cm2 , respectively). Cell culture experiments with B16F10 melanoma demonstrated that nanoencapsulation significantly increased TPT cytotoxicity (P < 0.05). TPT-NLC was more toxic than free TPT, with IC50 value of 5.74 μg/ml, whereas free TPT had an IC50 > 20 μg/ml. As skin permeated values of TPT from developed formulation (TPT-NLC) were superior to melanoma IC50, it can be extrapolated that chemotherapeutic permeated amounts may be sufficient for a therapeutic effect.

CONCLUSIONS:

TPT-NLC-HEC may be a valuable tool for the topical treatment of skin cancers.

• Authors: João Hélio Venâncio, Lígia Marquez Andrade, Najla Locatelli Santos Esteves, Lara Barroso Brito, Marize Campos Valadares, Gisele Augusto Rodrigues Oliveira, Eliana Martins Lima, Ricardo Neves Marreto, Tais Gratieri, Stephânia Fleury Taveira
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 69 Issue 10 Pg. 1318-1326 (Oct 2017) ISSN: 2042-7158 [Electronic] England
• PMID: 28703281 (Publication Type: Journal Article)
• Copyright: © 2017 Royal Pharmaceutical Society.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Hydrogels
• Lipids
• Topoisomerase I Inhibitors
• Topotecan

Topics

• Administration, Topical
• Animals
• Antineoplastic Agents (administration & dosage, metabolism)
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Drug Carriers (administration & dosage, metabolism)
• Hydrogels (administration & dosage, metabolism)
• Lipids (administration & dosage)
• Melanoma, Experimental (drug therapy, metabolism)
• Mice
• Nanoparticles (administration & dosage, metabolism)
• Organ Culture Techniques
• Skin Absorption (drug effects, physiology)
• Skin Neoplasms (drug therapy, metabolism)
• Swine
• Topoisomerase I Inhibitors (administration & dosage, metabolism)
• Topotecan (administration & dosage, metabolism)
• Treatment Outcome