Development of a long-acting tablet with ticagrelor high-loaded nanostructured lipid carriers.

Ticagrelor (TCG), an antiplatelet agent, has low solubility and permeability; thus, there are many trials to apply the pharmaceutical technology for the enhancement of TCG solubility and permeability. Herein, we have developed the TCG high-loaded nanostructured lipid carrier (HL-NLC) and solidified the HL-NLC to develop the oral tablet. The HL-NLC was successfully fabricated and optimized with a particle size of 164.5 nm, a PDI of 0.199, an encapsulation efficiency of 98.5%, and a drug loading of 16.4%. For the solidification of HL-NLC (S-HL-NLC), the adsorbent was determined based on the physical properties of the S-HL-NLC, such as bulk density, tap density, angle of repose, Hausner ratio, Carr's index, and drug content. Florite R was chosen because of its excellent adsorption capacity, excellent physical properties, and solubility of the powder after manufacturing. Using an S-HL-NLC, the S-HL-NLC tablet with HPMC 4 K was prepared, which is showed a released extent of more than 90% at 24 h. Thus, we have developed the sustained release tablet containing the TCG-loaded HL-NLC. Moreover, the formulations have exhibited no cytotoxicity against Caco-2 cells and improved the cellular uptake of TCG. In pharmacokinetic study, compared with raw TCG, the bioavailability of HL-NLC and S-HL-NLC was increased by 293% and 323%, respectively. In conclusion, we successfully developed the TCG high-loaded NLC tablet, that exhibited a sustained release profile and enhanced oral bioavailability.

Enhancement of S(+)-zaltoprofen oral bioavailability using nanostructured lipid carrier system.

Zaltoprofen is a nonsteroidal anti-inflammatory drug with poor oral bioavailability. S(+)-zaltoprofen (SZPF)-loaded nanostructured lipid carriers (NLCs) were prepared to enhance oral bioavailability. SZPF-loaded NLCs (NLC-SZPF) were prepared using the hot-melting homogenization method and optimized using the Box-Behnken design. The characterization of optimized NLC-SZPF, in vitro release, cytotoxicity, cellular uptake, ex vivo permeability, and pharmacokinetic parameters were evaluated to confirm the advantages of NLC formulation. NLC-SZPF with a diameter of 105.5 ± 1.2 nm had a high encapsulation efficiency of 99.84 ± 0.01%. NLC-SZPF showed a sustained-release profile, high biocompatibility, and high permeability across the intestinal tract. The relative bioavailability of NLC-SZPF was 431.3% compared with that of SZPF after oral administration to experimental rats. NLC-SZPF was successfully optimized using experimental designs to enhance the oral bioavailability of SZPF. Hence, NLC-SZPF could be a promising approach to overcome the poor oral bioavailability of SZPF.

Mannosylated poly(acrylic acid)-coated mesoporous silica nanoparticles for anticancer therapy.

Although mesoporous silica nanoparticles (MSNs) are widely used as anticancer drug carriers, unmodified MSNs induce off-target effects and at high doses, there are adverse effects of hemolysis because of the interaction with the silanol group on the surface and cells. In this study, we developed doxorubicin (DOX)-loaded MSNs coated with mannose grafted poly (acrylic acid) copolymer (DOX@MSNs-man-g-PAA) to enhance the hemocompatibility and target efficacy to cancer cells. This uniform nanosized DOX@MSNs-man-g-PAA showed sustained and pH-dependent drug release with improved hemocompatibility over the bare MSNs. The uptake of the DOX@MSN-man-g-PAA in breast cancer cells was significantly improved by mannose receptor-mediated endocytosis, which showed significant increasing intracellular ROS and changes in mitochondrial membrane potential. This formulation exhibited superior tumor-suppressing activity in the MDA-MB-231 cells inoculated mice. Overall, the present study suggested the possibility of the copolymer-coated MSNs as drug carriers for cancer therapy.

Preparation and evaluation of rapid disintegrating formulation from coated microneedle.

Microneedles (MNs), one of the transdermal drug delivery systems, have received extensive interest as an alternative to parenteral or parenteral administrations. For the successful drug delivery of coated MNs, the coated drug or chemical of MNs should be dissolved by skin's interstitial fluid and completely released from the MNs. Thus, the rapid disintegration of the drug from MNs plays a crucial role in ideal drug delivery of MNs. In this study, we developed the rapid disintegration coating formulation to reduce the application time of MN. The rapid disintegration MN was developed using polymers (PVA or HPMC), glycerol, croscarmellose sodium, tween 80, and Brij, as thickener, plasticizer, disintegrating agent, and surfactants, respectively. HPMC MN showed the burst release and rapid disintegration. Moreover, the drug from HPMC MN was successfully delivered into porcine skin within 1 min. In toxicological evaluation, the HPMC MN did not alter the liver and kidney function. Besides, HPMC MN did not induce the acute inflammation and change of skin structure after the application on rat skin. Thus, the coating formulation in this study could be one of the options for the development of safe and rapid disintegration MN.