Background: The need for parenteral administration of arteether (ART) as intramuscular
(IM) injection for three consecutive days often proves a major constraint for
patient compliance. The present study reports development of an in situ IM implant to
provide sustained release of ART over 72h.
Objective: The development of self microemulsifying drug delivery system (SMEDDS)
based lyotropic liquid crystalline preconcentrates (LLCPr) comprising oil, surfactant and
cosurfactants with a biodegradable polymer (P-LLCPr) which undergo rapid transition to
liquid crystalline phase (LCP) to form an in situ gel following IM injection.
Methods: The P-LLCPr was prepared by mixing oil and surfactant. PLGA was dissolved
in cosurfactant, added to this blend and vortex was mixed. The LLCPr (without polymer)
and P-LLCPr were evaluated for conversion into LCP by polarization optical microscopy
(POM), XRD, gel strength, particle size, zeta potential and sustained release by ex vivo
method in muscle of G. domesticus.
Results: POM and XRD study confirmed the formation of anisotropic LCP. A force of
<25N revealed good injectability of the LLCPr and P-LLCPr in vitro, and ex vivo in the
extensor digitorum longus (EDL) muscle of G. domesticus. Implant formation was observed
both in vitro and ex vivo. The P-LLCPr formed a stiff gel which exhibited a 4 fold
enhancement in gel strength compared to LLCPr. The particle size of P-LLCPr was 120 ±
1.5nm and zeta potential -14.56 mV. The ex vivo release method in EDL muscle, developed
to mimic in vivo conditions revealed 100% release in <24 h from ART solution and
LLCPr. The P-LLCPr however exhibited sustained release of ART for >48h.
Conclusion: The sustained release P-LLCPr of ART suggests great promise as a single
shot therapy for the treatment of malaria with enhanced patient compliance.