Combination of Phospholipid Complex and Submicron Emulsion Techniques for Improving Oral Bioavailability and Therapeutic Efficacy of Water-Insoluble Drug

Abstract

Water-insoluble drugs cannot be absorbed effectively through the gastrointestinal tract due to insufficient solubility and often face the problems of low bioavailability and poor therapeutic efficacy. To overcome these biopharmaceutical challenges, lipid-based formulations were suggested and have been researched in recent years. In this study, we used atorvastatin as a model drug to prepare a phospholipid complex prodrug system to upgrade its lipophilicity and further developed a drug loaded submicron emulsion to improve its in vivo bioavailability. The mean particle size and zeta potential of submicron emulsion were 122.7 nm and -22.7 mV. Intestinal absorption of atorvastatin from submicron emulsion was significantly improved compared with free drug, and the absorption rate constant ( K) and apparent permeability coefficients ( P) increase 2.88-fold and 2.45-fold, respectively. After oral administration, the atorvastatin plasma concentration of the emulsion group was much higher than that of free drug and the area under the curve (AUC) reached to 4.033 mg/L·h (2.58-fold). In vivo pharmacodynamics results revealed that atorvastatin submicron emulsion showed excellent antihyperlipidemia efficacy by reducing the total cholesterol, triglyceride, and low density lipoprotein cholesterol (LDL-cholesterol) levels and simultaneously increasing the high density lipoprotein cholesterol (HDL-cholesterol) level in comparison with Lipitor. In conclusion, drug-phospholipid complex loaded submicron emulsion was a promising oral delivery system for improving in vivo absorption behavior and therapeutic efficacy for water-insoluble drugs.

<p>Phospholipid complex based nanoemulsion system for oral insulin delivery: preparation, in vitro, and in vivo evaluations</p>

“…Hence, the phospholipid complex method was utilized to improve the liposolubility of insulin to load into the oil phase of nanoemulsion in this study. As shown in previous studies, the formation of the drug-phospholipid complex could improve the lipophilicity of the drugs 16,17. Moreover, Cui et al, demonstrated that insulin could be successfully complexed with phospholipid and solubilized within the hydrophobic phase 18.…”

Recent Advances in the Structural Design of Photosensitive Agent Formulations Using “Soft” Colloidal Nanocarriers

“…According to those studies, the obtained formulation exhibits improved oral absorption and enhanced cytotoxic action in metastatic breast tumor cell lines. [193] Abbreviations: CLSM, confocal laser scanning microscopy; D H , hydrodynamic diameter; DSC, differential scanning calorimetry; EE, entrapment efficiency; FTIR, Fourier transform infrared spectroscopy; HPLC, high performance liquid chromatography; NLC, nanostructured lipid carrier; NMR, nuclear magnetic resonance; PDT, photodynamic therapy; PLGA, poly(lactic-co-glycolic acid); SELFs, solid self-emulsifying lipid formulations; SLN, solid lipid nanoparticle; SNEDDS, self-nanoemulsifying drug delivery systems; STED, stimulated emission depletion microscopy; TPGS, D-α-tocopherol polyethylene glycol 1000 succinate; XRPD, X-ray powder diffraction.…”

“…Statins are very well tolerated groups of photosensitive drugs used as lipid-lowering substances with outstanding therapeutic properties and safety profiles [ 196 ]. The literature reports a phospholipid complex system consisting of atorvastatin, incorporated in a nanoemulsion [ 193 ]. Elmowafy et al [ 181 ] prepared other vehicles, such as the NLCs loaded with atorvastatin to improve the oral bioavailability and sustain release of that active compound.…”

Preparation and preliminary pharmacokinetics study of GNA-loaded zein nanoparticles

“…At the same time, these nano‐drug delivery systems were all carried by intravenous administration. Compared with intravenous administration, oral administration highlights more advantages for patients as a non‐invasive route of drug delivery with economic benefit, low toxicity and good compliance . Therefore, we developed a novel oral formulation of GNA, which avoids the irritation caused by intravenous administration.…”

“…Compared with intravenous administration, oral administration highlights more advantages for patients as a non-invasive route of drug delivery with economic benefit, low toxicity and good compliance. [16] Therefore, we developed a novel oral formulation of GNA, which avoids the irritation caused by intravenous administration. Meanwhile, there were low toxic side effects benefiting from less excipients and surfactants used during the preparation of the formulation.…”