Improvement of Oral Bioavailability of N-251, a Novel Antimalarial Drug, by Increasing Lymphatic Transport with Long-Chain Fatty Acid-Based Self-Nanoemulsifying Drug Delivery System

2015 ◽  
Author(s):  
Chikako Imada ◽  
Takuma Takahashi ◽  
Makoto Kuramoto ◽  
Kazufumi Masuda ◽  
Ken-ichi Ogawara ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fatty Acid ◽  
Drug Delivery System ◽  
Delivery System ◽  
Antimalarial Drug ◽  
Oral Bioavailability ◽  
Chain Fatty Acid ◽  
Lymphatic Transport ◽  
Long Chain Fatty Acid ◽  
Long Chain

Intestinal delivery in a long-chain fatty acid formulation enables lymphatic transport and systemic exposure of orlistat

2021 ◽  
Vol 596 ◽  
pp. 120247
Author(s):  
Given Lee ◽  
Sifei Han ◽  
Zijun Lu ◽  
Jiwon Hong ◽  
Anthony R.J. Phillips ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Systemic Exposure ◽  
Chain Fatty Acid ◽  
Lymphatic Transport ◽  
Long Chain Fatty Acid ◽  
Intestinal Delivery ◽  
Acid Formulation ◽  
Long Chain

scholarly journals pH-sensitive dual drug loaded janus nanoparticles by oral delivery for multimodal analgesia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Liu ◽  
Wendong Yao ◽  
Xiaowei Xie ◽  
Jianqing Gao ◽  
Xiaoyang Lu
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Bioavailability ◽  
Multimodal Analgesia ◽  
Laser Scanning Microscopy ◽  
Lymphatic Transport ◽  
Janus Nanoparticles ◽  
Cavity Structure ◽  
Dual Drug

Abstract Background Based on the concept of “multimodal analgesia”, a novel dual drug delivery system was designed to achieve synergistic analgesia between najanajaatra venom protein (αCT) and resveratrol (Res). In order to meet the joint loading of two drugs with different physicochemical properties without affecting each other, an oral Janus nanoparticle (JNP) with a unique cavity structure and synergistic drug delivery was constructed using an improved double emulsion solvent evaporation method, and combined with low-molecular-weight chitosan/sodium alginate and PLGA to achieve its pH-responsive. Results The synthesized αCT/Res-JNPs are homogeneous in shape, with a two-compartment structure, approximately 230 nm in size, and zeta potential of 23.6 mV. Drug release assayed in vitro show that JNP was stable in simulated gastric juice (pH = 1.2) but was released in phosphate buffer saline (pH = 7.4). After intragastric administration in rats, PK evaluation showed that αCT/Res-JNPs could significantly improve the oral bioavailability, and the simultaneous encapsulation of the two drugs had no significant interaction on PK parameters. An obvious synergistic analgesic effects of αCT/Res-JNPs was confirmed in a spinal cord injury and acute pain model. Confocal laser scanning microscopy and single-pass intestinal perfusion model provided strong evidence that αCT/Res-JNPs could pass through intestinal epithelial cells, and the endocytosis pathway was mainly involved in the mediation and pinocytosis of reticulin. The concentrations of αCT and Res from αCT/Res-JNP in lymphatic transport were only about 8.72% and 6.08% of their blood concentrations at 1 h, respectively, which indicated that lymphatic transport in the form of JNP has limited advantages in improving the oral bioavailability of Res and αCT. Cellular uptake efficiency at 4 h was about 10–15% in Caco-2 cell lines for αCT/Res-JNP, but was reduced to 7% in Caco-2/HT29-MTX co-culture models due to the hindrance by the mucus layers. Approximately 12–17% of αCT/Res-JNP were transported across Caco-2/HT29-MTX/Raji monolayers. The cumulative absorption of JNP in three cell models was higher than that of free drug. Conclusions This study investigated the contribution of Janus nanoparticles in oral absorption, and provide a new perspective for oral administration and analgesic treatment of dual drug delivery system containing peptide drugs. Graphic Abstract

scholarly journals Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes

2000 ◽  
Vol 41 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Karin A. J.M. van der Lee ◽  
Michaël M. Vork ◽  
Johan E. De Vries ◽  
Peter H.M. Willemsen ◽  
Jan F.C. Glatz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Cardiac Myocytes ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acid ◽  
Induced Changes ◽  
Long Chain
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