TY - JOUR
T1 - Adapting clofazimine for treatment of cutaneous tuberculosis by using self-double-emulsifying drug delivery systems
AU - van Staden, Daniélle
AU - Haynes, Richard K.
AU - Viljoen, Joe M.
N1 - Funding Information:
Acknowledgments: The authors would like to thank the Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, South Africa for the financial contribution to this project.
Funding Information:
Funding: This work is funded by the the South African National Research Foundation (SA NRF) grant (UID 129135) (J.M.V.).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/6/15
Y1 - 2022/6/15
N2 - Although chemotherapeutic treatment regimens are currently available, and consider-able effort has been lavished on the development of new drugs for the treatment of tuberculosis (TB), the disease remains deeply intractable and widespread. This is due not only to the nature of the life cycle and extraordinarily disseminated habitat of the causative pathogen, principally Mycobacterium tuberculosis (Mtb), in humans and the multi-drug resistance of Mtb to current drugs, but especially also to the difficulty of enabling universal treatment of individuals, immunocompromised or otherwise, in widely differing socio-economic environments. For the purpose of globally eliminating TB by 2035, the World Health Organization (WHO) introduced the “End-TB” initiative by employing interventions focusing on high impact, integrated and patient-centered approaches, such as individualized therapy. However, the extraordinary shortfall in stipulated aims, for example in actual treatment and in TB preventative treatments during the period 2018–2022, latterly and greatly exacerbated by the COVID-19 pandemic, means that even greater pressure is now placed on enhancing our scientific understanding of the disease, repurposing or repositioning old drugs and developing new drugs as well as evolving innovative treatment methods. In the specific context of multidrug resistant Mtb, it is furthermore noted that the incidence of extra-pulmonary TB (EPTB) has significantly increased. This review focusses on the potential of utilizing self-double-emulsifying drug delivery systems (SDEDDSs) as topical drug delivery systems for the dermal route of administration to aid in treatment of cutaneous TB (CTB) and other mycobacterial infections as a prelude to evaluating related systems for more effective treatment of CTB and other mycobacterial infections at large. As a starting point, we consider here the possibility of adapting the highly lipophilic riminophenazine clofazimine, with its potential for treatment of multi-drug resistant TB, for this purpose. Additionally, recently reported synergism achieved by adding clofazimine to first-line TB regimens signifies the need to consider clofazimine. Thus, the biological effects and pharmacology of clofazimine are reviewed. The potential of plant-based oils acting as emulsifiers, skin penetration enhancers as well as these materials behaving as anti-microbial components for transporting the incorporated drug are also discussed.
AB - Although chemotherapeutic treatment regimens are currently available, and consider-able effort has been lavished on the development of new drugs for the treatment of tuberculosis (TB), the disease remains deeply intractable and widespread. This is due not only to the nature of the life cycle and extraordinarily disseminated habitat of the causative pathogen, principally Mycobacterium tuberculosis (Mtb), in humans and the multi-drug resistance of Mtb to current drugs, but especially also to the difficulty of enabling universal treatment of individuals, immunocompromised or otherwise, in widely differing socio-economic environments. For the purpose of globally eliminating TB by 2035, the World Health Organization (WHO) introduced the “End-TB” initiative by employing interventions focusing on high impact, integrated and patient-centered approaches, such as individualized therapy. However, the extraordinary shortfall in stipulated aims, for example in actual treatment and in TB preventative treatments during the period 2018–2022, latterly and greatly exacerbated by the COVID-19 pandemic, means that even greater pressure is now placed on enhancing our scientific understanding of the disease, repurposing or repositioning old drugs and developing new drugs as well as evolving innovative treatment methods. In the specific context of multidrug resistant Mtb, it is furthermore noted that the incidence of extra-pulmonary TB (EPTB) has significantly increased. This review focusses on the potential of utilizing self-double-emulsifying drug delivery systems (SDEDDSs) as topical drug delivery systems for the dermal route of administration to aid in treatment of cutaneous TB (CTB) and other mycobacterial infections as a prelude to evaluating related systems for more effective treatment of CTB and other mycobacterial infections at large. As a starting point, we consider here the possibility of adapting the highly lipophilic riminophenazine clofazimine, with its potential for treatment of multi-drug resistant TB, for this purpose. Additionally, recently reported synergism achieved by adding clofazimine to first-line TB regimens signifies the need to consider clofazimine. Thus, the biological effects and pharmacology of clofazimine are reviewed. The potential of plant-based oils acting as emulsifiers, skin penetration enhancers as well as these materials behaving as anti-microbial components for transporting the incorporated drug are also discussed.
KW - clofazimine
KW - cutaneous tuberculosis
KW - drug delivery
KW - multi-drug resistant TB
KW - permeation enhancers
KW - self-double-emulsifying drug delivery system
KW - topical administration
KW - tuberculosis
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UR - http://www.scopus.com/inward/citedby.url?scp=85132770078&partnerID=8YFLogxK
U2 - 10.3390/antibiotics11060806
DO - 10.3390/antibiotics11060806
M3 - Review article
C2 - 35740212
AN - SCOPUS:85132770078
SN - 2079-6382
VL - 11
JO - Antibiotics
JF - Antibiotics
IS - 6
M1 - 806
ER -