TY - JOUR
T1 - Intranasal artesunate-loaded nanostructured lipid carriers
T2 - A convenient alternative to parenteral formulations for the treatment of severe and cerebral malaria
AU - Agbo, Chinazom
AU - Ugwuanyi, Timothy
AU - Ugwuoke, Wilfred
AU - McConville, Christopher
AU - Attama, Anthony
AU - Ofokansi, Kenneth
PY - 2021/6/10
Y1 - 2021/6/10
N2 - Early treatment with parenteral antimalarials is key in preventing deaths and complications associated with severe and cerebral malaria. This can be challenging in 'hard-to-reach' areas in Africa where transit time to hospitals with facilities to administer drugs parenterally can be more than 6 h. Consequently, the World Health Organization has recommended the use of artesunate (ATS) suppositories for emergency treatment of patients, however, this treatment is only for children under 6 years. The intranasal route (INR) can provide a safe and effective alternative to parenteral and rectal routes for patients of all ages; thus, reducing delays to the initiation of treatment. Hence, we designed ATS-loaded nanostructured lipid carriers (NLCs) for intranasal administration. ATS-NLCs were formulated using varying concentrations of lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising a 1:2 ratio of Phospholipon ® 90H and lipids (Softisan ® 154 or Compritol ®). ATS-NLCs were spherical, and the small sizes of ATS-NLCs obtained for some formulations (76.56 ± 1.04 nm) is an indication that ATS-NLCs can pass through the nasal mucosa and reach the brain or systemic circulation. Encapsulation efficiency of ATS in NLCs was ≥70% for all formulations. ATS-NLCs achieved up to 40% in vitro drug release in 1 h, while ex vivo permeation studies revealed that formulating ATS as NLCs enhanced permeation through pig nasal mucosa better than drug solution. Most importantly, the activity and reduction in parasitaemia [in mice infected with Plasmodium berghei ANKA in a murine cerebral malaria model] by ATS-NLCs administered through the INR (54.70%, 33.28%) was comparable to intramuscular administration (58.80%, 42.18%), respectively. Therefore, intranasal administration of NLCs of ATS has great potentials to serve as a satisfactory alternative to parenteral administration for the treatment of severe and cerebral malaria in both adults and children in remote areas of sub-Saharan Africa.
AB - Early treatment with parenteral antimalarials is key in preventing deaths and complications associated with severe and cerebral malaria. This can be challenging in 'hard-to-reach' areas in Africa where transit time to hospitals with facilities to administer drugs parenterally can be more than 6 h. Consequently, the World Health Organization has recommended the use of artesunate (ATS) suppositories for emergency treatment of patients, however, this treatment is only for children under 6 years. The intranasal route (INR) can provide a safe and effective alternative to parenteral and rectal routes for patients of all ages; thus, reducing delays to the initiation of treatment. Hence, we designed ATS-loaded nanostructured lipid carriers (NLCs) for intranasal administration. ATS-NLCs were formulated using varying concentrations of lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising a 1:2 ratio of Phospholipon ® 90H and lipids (Softisan ® 154 or Compritol ®). ATS-NLCs were spherical, and the small sizes of ATS-NLCs obtained for some formulations (76.56 ± 1.04 nm) is an indication that ATS-NLCs can pass through the nasal mucosa and reach the brain or systemic circulation. Encapsulation efficiency of ATS in NLCs was ≥70% for all formulations. ATS-NLCs achieved up to 40% in vitro drug release in 1 h, while ex vivo permeation studies revealed that formulating ATS as NLCs enhanced permeation through pig nasal mucosa better than drug solution. Most importantly, the activity and reduction in parasitaemia [in mice infected with Plasmodium berghei ANKA in a murine cerebral malaria model] by ATS-NLCs administered through the INR (54.70%, 33.28%) was comparable to intramuscular administration (58.80%, 42.18%), respectively. Therefore, intranasal administration of NLCs of ATS has great potentials to serve as a satisfactory alternative to parenteral administration for the treatment of severe and cerebral malaria in both adults and children in remote areas of sub-Saharan Africa.
KW - Severe malaria
KW - Cerebral malaria
KW - Artesunate
KW - Intranasal route
KW - Nanostructured lipid carriers
KW - Solidified reverse micellar solutions
U2 - 10.1016/j.jconrel.2021.04.020
DO - 10.1016/j.jconrel.2021.04.020
M3 - Article
SN - 0168-3659
VL - 334
SP - 224
EP - 236
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -