Related Experiment Video
Updated: Aug 26, 2025
09:31
Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres
Published on: November 5, 2016
7.3K
Ionic co-aggregates (ICAs) based oral drug delivery: Solubilization and permeability improvement
Xianzi Zheng1, Zhezheng Fang1, Weizi Huang1
1Key Laboratory of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai 201203, China.
Acta Pharmaceutica Sinica. B
|October 10, 2022
Summary
Ionic co-aggregates (ICAs) improve oral drug absorption for poorly soluble compounds. Choline oleate ICAs demonstrated superior paclitaxel delivery and intestinal retention compared to traditional micelles.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Physical Chemistry
Background:
- Poorly water-soluble drugs present significant challenges in pharmaceutical development.
- Ionic co-aggregates (ICAs) formed by lipophilic fatty acid anions and hydrophilic choline cations exhibit surface activity.
- These ICAs can enhance drug solubility and permeability.
Purpose of the Study:
- To investigate the potential of choline oleate-based ICAs for enhancing the oral absorption of poorly water-soluble drugs.
- To compare the efficacy of ICAs with conventional drug delivery systems, such as micelles.
- To evaluate the in vivo transport and cellular interaction of intact ICAs.
Main Methods:
- Preparation and characterization of choline oleate-based ICAs.
- In vivo oral administration of paclitaxel (PTX) formulated with ICAs and cremophor EL-based micelles (MCs).
- Utilized aggregation-caused quenching probes for tracking ICAs in vivo and in cellular studies.
- Performed ex vivo imaging of major organs and intestinal tracts.
- Conducted cellular uptake and transport studies.
Main Results:
- Choline oleate ICAs significantly enhanced the oral absorption of paclitaxel compared to cremophor EL-based micelles.
- Aggregation-caused quenching probes successfully tracked intact ICAs during in vivo transport and cellular interactions.
- ICAs exhibited prolonged intestinal retention, suggesting superior in vivo solubilizing capability.
- Ex vivo imaging and cellular studies confirmed the transepithelial transport of intact ICAs.
- Enhanced absorption of paclitaxel was observed in conjunction with ICA transport.
Conclusions:
- Ionic co-aggregates (ICAs) represent a promising drug delivery system for poorly water-soluble drugs.
- The combination of lipophilic and hydrophilic ions in ICAs effectively enhances both drug solubility and permeability.
- Choline oleate ICAs show significant potential for improving oral drug delivery and therapeutic outcomes.
Keywords:
Aggregation-caused quenchingBioavailabilityCaco-2In vivo fateIonic co-aggregatesMolecular dynamics simulationOralPaclitaxelMore Related Videos
Related Concept Videos
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
967
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...
967
01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
249
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...
249
01:22Factors Influencing Drug Absorption: Physicochemical Parameters
395
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.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
395
01:27Factors Influencing Drug Absorption: Drug Dissolution
656
The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
656
01:16Drug Delivery: Overview
373
The selection of a drug's delivery route depends upon its physicochemical properties, including lipid or water solubility and ionization, as well as the therapeutic requirement, such as immediate or sustained effect. These routes can be divided into three primary categories: enteral, parenteral, and topical.
Enteral delivery involves administering drugs directly through swallowing, sublingual placement, or buccal application. Orally administered drugs predominantly navigate the...
Enteral delivery involves administering drugs directly through swallowing, sublingual placement, or buccal application. Orally administered drugs predominantly navigate the...
373
01:18Drug Delivery: Enteral Route
647
The enteral drug administration involves three primary routes: oral, sublingual, and buccal. Oral ingestion is the most prevalent, safe, economical, and convenient method for drug administration. However, it has certain drawbacks, including limited absorption due to the drug's low water solubility or poor membrane permeability, possible emesis from GI mucosa irritation, destruction of drugs by digestive enzymes or low gastric pH, and irregular absorption along with food or other drugs.
647