Preparation and characterization of tetrandrine-phospholipid complex loaded lipid nanocapsules as potential oral carriers

Abstract

Background Tetrandrine is an active constituent that is extracted from the root tuber of the Chinese herb Stephania tetrandra S. Moore. It has shown various pharmacological effects, such as antitumor activity, multidrug resistance reversal, and hepatic fibrosis resistance. In clinical applications, it has been used to treat hypertension, pneumosilicosis, and lung cancer. However, the poor water solubility of tetrandrine has limited its application. In this study, a newly emerging oral drug carrier of phospholipid complex loaded lipid nanocapsules was developed to improve the oral bioavailability of tetrandrine. Methods The phospholipid complex was prepared with the solvent-evaporation method to enhance the liposolubility of tetrandrine. The formation of the phospholipid complex was confirmed with a solubility study, infrared spectroscopy, and a differential scanning calorimetry (DSC) analysis. The tetrandrine-phospholipid complex loaded lipid nanocapsules (TPC-LNCs) were prepared using the phase inversion method. Lyophilization was performed with mannitol (10%) as a cryoprotectant. TPC-LNCs were characterized according to their particle size, zeta potential, encapsulation efficiency, morphology by transmission electron microscopy, and crystallinity by DSC. In addition, the in vitro release of tetrandrine from TPC-LNCs was examined to potentially illustrate the in vivo release behavior. The in vivo bioavailability of TPC-LNCs was studied and compared to tetrandrine tablets in rats. Results The liposolubility of tetrandrine in n -octanol improved from 8.34 μg/mL to 35.64 μg/mL in the tetrandrine-phospholipid complex. The prepared TPC-LNCs were spherical-shaped particles with a small size of 40 nm and a high encapsulation efficiency of 93.9%. DSC measurements revealed that the crystalline state was less ordered in lipid nanocapsules. The in vitro release study demonstrated a fast release of approximately 25% in the first 1 hour, which was followed by a sustained release of 70% over 12 hours. The relative bioavailability of TPC-LNCs compared to that of tablets was 208%, indicating a significant improvement in the oral absorption of tetrandrine. Conclusion The TPC-LNCs system developed in this study is a promising carrier that improves the oral bioavailability of tetrandrine in rats. The phospholipid complex loaded lipid nanocapsules have great potential for use as an oral drug delivery system for moderately lipophilic drugs that are encapsulated in the lipid nanocapsules.

A novel tetrandrine-loaded chitosan microsphere: characterization and in vivo evaluation

“…Tetrandrine (TED, CAS:518-34-3), the major active constituent of the Chinese herb Stephania tetrandra S. Moore, is a bisbenzylisoquinoline alkaloid. Clinically, TED has been found to be effective for the treatment of inflammation, 1 , 2 pneumosilicosis, 3 and antitumor activity. 4 – 6 Numerous studies have reported that TED also acts as a nonselective calcium channel blocker 7 , 8 and calmodulin antagonist.…”

“…In recent years, many pharmaceutical methods have been investigated to improve the bioavailability of TED, such as lipid nanocapsules, 3 nanoparticles, 14 ethosomes, 15 and microspheres. 16 Microsphere technology has been widely used in the preparation of sustained formulations in order to maintain targeted concentration in vivo for a sustained period of time.…”

Self-Nanoemulsifying Drug Delivery System of Tetrandrine for Improved Bioavailability: Physicochemical Characterization and Pharmacokinetic Study

“…The average droplet size of the optimal formulation was 19.75±0.37 nm, and the average zeta-potential was 1.87±0.26 mv. With other new formulations of Tet such as nanoparticles (Tet-loaded PVP-b-PCL nanoparticles) [ 35 ], nanocapsules (tetrandrine-phospholipid complex loaded lipid nanocapsules) [ 22 ], and microsphere (tetrandrine-loaded chitosan microsphere) [ 25 ], SNEDDS-Tet has a smaller particle size (size ranges of nanocapsules and microsphere: from 40 nm to 15 μ m), equivalent solubility (solubility of nanocapsules in water: 8.28 ± 0.37 μ g/mL), and a longer mean residence time (MRT of nanocapsules nanocapsules: 8.39 ± 1.532 h).…”

“…Although Tet has potentially considerable value in clinic, some problems have arisen that have limited its clinical application. In general, a large dose (6 to 15 tablets per day) is required for the current commercially available tablets [ 22 ]. Additionally, Tet's poor solubility in physiological environment (Tet saturation=0.015 mg/mL in pH 7.4 phosphate buffered saline (PBS)) caused by the presence of a quaternary ammonium cation [ 23 ] contributes to its low and variable oral bioavailability, gastric intestine and kidney damage, and bad patient compliance [ 24 ].…”

<p>Novel Drug Delivery Systems for Loading of Natural Plant Extracts and Their Biomedical Applications</p>

“…54 More examples of herbal loaded NE are presented in Table 1. [57][58][59][60][61][62] Lipid Drug Conjugate (LDC) or Polymer Drug Conjugate (PDC) The union of agents with polymers is a new approach to modify drug property and its pharmacokinetics. LDCs are lipidic drugs that covalently or noncovalently coupled to a lipid moiety, such as diglyceride, phosphoglyceride and fatty acid (Figure 4).…”