In vitro and in vivo development of a topical drug for the treatment of equine skin cancer – based on naturally occurring and synthetically modified substances in plane bark

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• Publisher: Cuvillier Verlag
• Year: 2021
• eBook ISBN:
  9783736964327
• Print ISBN:
  9783736974326
• Edition: 1

Equine sarcoids (ES) and equine malignant melanoma (EMM) are among the tumors affecting horses diagnosed most frequently. Both cutaneous neoplasms can be a significant cause of economic losses, morbidity and mortality in the animals. The treatment of equine skin cancer can be challenging and established, evidence-based therapies resulting in sustained tumor regression are rare. The pentacyclic, lupane-type triterpenes betulinic acid (BA) and betulin can be isolated from many botanical sources, predominantly from the bark of white birch and plane trees. In addition to various biological properties, they have gained attention mainly due to their anticancer features. Within the framework of the current PhD project, the compounds BA, BA derivative NVX-207, and betulin derivative betulinyl-bis-sulfamate were assessed in various in vitro and in vivo studies for their potential as a topical therapy for ES and EMM. In conclusion, the results generated from cell culture experiments, skin permeation assays and studies in the target species are promising. Further advancement of the investigational medicinal products studied herein could lead to an effective topical and marketable, novel drug which helps to relieve suffering and, consequently, improve the welfare of equine skin cancer patients.

Table of contents

• LIST OF ABBREVIATIONS
• SUMMARY
• ZUSAMMENFASSUNG
• 1. Introduction
• 1.1. The equine malignant melanoma
• 1.2. The equine sarcoid: an overview
• 1.3. Topical drug application
• 1.4. Naturally occurring substances in plane bark and their syntheticallymodified derivatives
• 1.5. Hypotheses and aims of the thesis
• 2. Manuscript I:Betulinic acid shows anticancer activity against equine melanoma cells andpermeates isolated equine skin in vitro
• 2.1. Supplemental data
• 3. Manuscript II:In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate asa topical treatment for equine skin cancer
• 4. Manuscript III:Concentration profiles and safety of topically applied betulinic acid andNVX-207 in eight healthy horses – A randomized, blinded, placebocontrolled,crossover pilot study
• 5. Manuscript IV:Effects of topically applied betulinic acid and NVX-207 on early stageequine melanoma – A prospective, randomized, double-blind, placebocontrolledpilot study
• 6. General discussion
• 6.1. Summarized findings
• 6.2. Interpretation of the findings
• 7. Major findings and conclusions
• 8. Future perspectives
• 9. References
• Affidavit
• Acknowledgements