Study on Formulation, in vivo Exposure, and Passive Targeting of Intravenous Itraconazole Nanosuspensions

Abstract

The pharmacokinetic profile of a drug can be different when delivered as a nanosuspension compared with a true solution, which may in turn affect the therapeutic effect of the drug. The goal of this study was to prepare itraconazole nanosuspensions (ITZ-Nanos) stabilized by an amphipathic polymer, polyethylene glycol-poly (benzyl aspartic acid ester) (PEG-PBLA), by the precipitation-homogenization, and study the pharmacokinetic profile of the ITZ-Nanos. The particle size and morphology of nanosuspensions were determined by Zetasizer and field emission scanning electron microscope (SEM), respectively. The dissolution profile was evaluated using a paddle method according to Chinese Pharmacopoeia 2015. The level of ITZ in plasma and tissues was measured by a HPLC method. The optimized ITZ-Nanos had an average particle size of 268.1 ± 6.5 nm and the particles were in a rectangular form. The dissolution profile of ITZ-Nanos was similar to that of commercial ITZ injections, with nearly 90% ITZ released in the first 5 min. The ITZ-Nanos displayed different pharmacokinetic properties compared with the commercial ITZ injections, including a decreased initial drug concentration, increased plasma half-life and mean residence time (MRT), and increased concentration in the liver, lung, and spleen. The ITZ-Nanos can change the in vivo distribution of ITZ and result in passive targeting to the organs with mononuclear phagocyte systems (MPS).

Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages

“…Additionally, the results with bare-NP can be related to the phenomenon where the endocytosis of macrophages of foreign objects can be modulated by characteristics such as size, shape, surface charge, and hydrophobicity/hydrophilicity because they regulate the interaction with physiological proteins and the protein corona formation [74][75][76]. In our case, it was the proteins from the Fetal Bovine serum (FBS).…”

Preparation of oxymatrine n-butyl polycyanoacrylate nanoparticles and its hepatoprotective effects in ob/ob mice

“…From the perspective of medication safety, the smallest capillary diameter of the human body is about 4 µm, so the size of the intravenously injected nanoparticles should be less than this limit. From the perspective of in vivo targeting, particles with the size being less than 50nm can penetrate the liver endothelium or reach the spleen, bone marrow, or tumor cells through the lymphatic system; particles with the size being more than 100 nm-2 µm can be phagocytized by the reticuloendothelial system (RES), those with the size within 2-7 µm ingested by the capillary vascular network are accumulated in the lungs, spleen, and liver, and those with the size within 7-12 µm are more mechanically blocked by the lungs (25). The OM-PBCA-NPs prepared in this study for liver targeting has the particle size of (104.1 ± 29.11) nm and narrow distribution, which met the requirements of liver targeting particle size.…”

Kajian Pengembangan Sediaan Nanosuspensi Untuk Penghantaran Intravena Obat Sukar Larut Air

“…Sistem nanosuspensi dapat membantu menghantarkan obat melalui rute intravena, dengan memperkecil ukuran partikel sehingga mencegah terjadinya penyumbatan aliran darah dan meningkatkan kelarutan (17). Penggunaan obat secara intravena dengan menggunakan bahan penstabil (polimer/surfaktan) dalam formulasi nanosuspensi harus sangat diperhatikan guna menjamin keamanan penggunaan (18).…”

“…Dari 20 artikel tersebut diketahui ada 3 duplikasi artikel, sehingga yang akhirnya proses adalah 17 artikel. Dari seluruh artikel selanjutnya dilakukan ekstraksi data yang berkaitan dengan jenis penstabil yang digunakan, profil disolusi, pelepasan, dan farmakokinetika zat aktif, serta kajian keamanan penggunaan secara intravena (18,19).…”