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Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
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Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
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The pharmacokinetic journey of oral drugs begins with a crucial first pass through the hepatic portal system, called the first-pass effect. This first pass significantly impacts bioavailability — the proportion of a drug that enters systemic circulation and is available for therapeutic action. The primary route sees the drug absorbed by intestinal membranes and then shunted to the liver via the hepatic portal vein. Here, pre-systemic elimination occurs as drugs face metabolism or biliary...
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The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
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Lipid nanoparticles for enhancing oral bioavailability.

Anushareddy Gangavarapu1, Lillian V Tapia-Lopez2, Barnali Sarkar2

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Lipid nanoparticles (LNPs) enhance oral drug delivery for poorly absorbed medications. These versatile systems improve bioavailability by overcoming gastrointestinal challenges and utilizing lymphatic pathways.

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Area of Science:

  • Pharmaceutical Sciences
  • Nanotechnology
  • Drug Delivery Systems

Background:

  • Lipid nanoparticles (LNPs) are emerging as promising drug delivery systems for biopharmaceutics classification system (BCS) class II and IV drugs.
  • These drugs often exhibit poor oral absorption and bioavailability due to degradation and low permeability.
  • LNPs, including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), offer a solution by encapsulating diverse drug types.

Purpose of the Study:

  • To provide an update on lipid nanoparticles (LNPs) for enhancing the oral bioavailability of poorly permeable drugs.
  • To highlight the mechanisms by which LNPs improve drug absorption across gastrointestinal barriers.
  • To discuss the current challenges and future directions for LNP-based oral drug delivery.

Main Methods:

  • Review of recent literature on lipid nanoparticle formulations and their applications in oral drug delivery.
  • Analysis of LNP mechanisms including gastrointestinal transit, transmembrane absorption, and transport kinetics.
  • Exploration of computational tools used in LNP design and evaluation.

Main Results:

  • Lipid nanoparticles demonstrate significant potential in increasing the bioavailability of BCS class II and IV drugs.
  • LNPs utilize unique lipid properties (biodegradability, biocompatibility) and transport pathways to enhance drug absorption.
  • Selective lymphatic transport pathways contribute to improved drug bioavailability via LNPs.

Conclusions:

  • Lipid nanoparticles offer a versatile platform for improving oral drug delivery of challenging compounds.
  • Understanding LNP mechanisms across gastrointestinal hurdles is crucial for optimizing drug delivery.
  • Further research into LNP hurdles and future perspectives is essential for advancing oral drug delivery systems.