In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and -%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level.
Immunoliposomes (antibody-directed liposomes) are common pharmaceutical carriers for targeted drug delivery because of their unique ability to encapsulate both hydrophilic and hydrophobic therapeutic agents and due to their simple preparation. Wu et al . developed in vivo lung cancer targeted immunoliposomes using an anti-c-Met antibody [ 64 ]. The receptor for hepatocyte growth factor (HGF), c-Met, is abundantly expressed in 25% of non-small cell lung cancer patients, and activation of this protein is reported to trigger cancer cell proliferation, migration, and invasion [ 65 , 66 ]. Wu et al. prepared individual targeted therapeutic vehicles and imaging probes. First, an anti-c-Met single chain variable fragment (scFv) antibody was identified by phage display (Ms20, Kd value; nM), and cysteine residues were fused for site-direct conjugation with maleimide-modified PEG-terminated liposomal Dox. The resulting Ms20-conjugated liposomal Dox (Ms20-LD) was used as a therapeutic vehicle. Inorganic quantum dots (QD) were also utilized to prepare targeted diagnostic tools (Ms20-QD). Because c-Met expression appeared in angiogenic endothelium as well as in tumor cells [ 67 ], the dual targeting properties, including inhibition of tumor growth and prevention of angiogenesis, were observed in an Ms20-LD-injected H460-bearing SCID mouse xenograft model. In addition, Ms20-LD improved chemotherapeutic drug delivery by inhibiting c-Met-transient or c-Met-constitutive activation of cancer cells. An in vivo tumor homing study of Ms20-QD supported that Ms20 provided selective delivery to solid tumors and was potentially useful as a lung tumor targeted theranostic agent.