Polyester–Solid Lipid Mixed Nanoparticles with Improved Stability in Gastro-Intestinal Tract Facilitated Oral Delivery of Larotaxel

Abstract

The objective of this study was to investigate the role of core stability of nanoparticles on their performances in oral drug delivery. Solid lipids (Geleol Mono and Diglycerides Nf) were incorporated into nanoparticles composed of mPEG-b-PCL by the dialysis method. The prepared solid lipid loaded nanoparticles were found to be spherical nanoparticles with a core state and size distribution dependent on the amount of solid lipid incorporated. The critical aggregation concentrations of lipid-loaded nanoparticles were determined using pyrene fluorescence. Then, the stability of block copolymer in nanoparticles with different solid lipid contents was studied in simulated gastric fluid and simulated intestinal fluid. Solid lipids were found to stabilize nanoparticle cores by improving not only the thermodynamic stability (lowered CAC) of the nanoparticle but also the chemical stability of the block copolymer in the gastrointestinal environment. The stability of the loaded drug (larotaxel, LTX) in nanoparticles with different solid lipid contents was challenged by intestinal homogenate and rat liver microsome, and solid lipid loaded nanoparticles showed superior drug-protecting capability. Solid lipid incorporation exhibited limited influence on the cytotoxicity and cellular uptake but improved the transcytosis of nanoparticles in Caco-2 monolayers. The results of pharmacokinetic study indicated that core stabilization was helpful in promoting oral larotaxel absorption as the absolute bioavailability of LTX delivered by solid lipid loaded nanoparticles was found to be 13.17%, compared with that by the lipid-free nanoparticles (6.264%) and LTX solution (2.435%). Additionally, the results of biodistribution study indicated relatively higher particle integrity of solid lipid loaded nanoparticles, shown by slower liver and spleen accumulation rate, compared with its lipid-free counterpart. Overall, incorporation of solid lipids made the nanoparticles more suitable for oral drug delivery.

Optimization, and in vitro and in vivo evaluation of etomidate intravenous lipid emulsion

“…The brain, heart, liver, spleen, lungs, and kidneys were collected immediately. Each tissue was washed with ice-cold saline, cut into pieces, weighed, and homogenized thrice with 0.9% normal saline (w/v) (Shi et al., 2010 ; Gou et al., 2017 ). The samples were centrifuged at 5,000 rpm for 15 min.…”

Oral Administration of Starting Materials for In Vivo Synthesis of Antibacterial Gold Nanoparticles for Curing Remote Infections

“…The in vivo synthesis of nanomedicine may be performed by introducing the starting materials in the body via two main routes, one is by intravenous injection, another is by oral administration . The synthesis of nanomaterials in gastrointestinal tract faces a bigger challenge than that in the blood due to the strong acidic condition in the stomach, the numerous enzymes in the intestinal tract, as well as the interference from food. , However, more than 80% of drugs are taken orally for treating a variety of diseases − owing to the low risk of injection-caused infections, low systematic side effects, and straightforwardness in usage. − As a convenient tool, an oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. The oral route has been employed to deliver siRNA , and macromolecules effectively to treat diseases in the intestinal region.…”

“…4 The synthesis of nanomaterials in gastrointestinal tract faces a bigger challenge than that in the blood 5 due to the strong acidic condition in the stomach, the numerous enzymes in the intestinal tract, as well as the interference from food. 6,7 However, more than 80% of drugs are taken orally for treating a variety of diseases 8−11 owing to the low risk of injection-caused infections, low systematic side effects, 12 and straightforwardness in usage. 13−15 As a convenient tool, an oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake.…”

Development of Epirubicin-Loaded Biocompatible Polymer PLA–PEG–PLA Nanoparticles: Synthesis, Characterization, Stability, and In Vitro Anticancerous Assessment

“…Furthermore, the exceptional properties of nano-based drug delivery systems (DDSs) enable them to be formulated in different dosage forms requiring various stability properties [25][26][27][28][29][30][31]. Even though nano-based DDSs have various advantages, it is challenging to manufacture them due to their stability issues.…”