Related Experiment Video
Updated: Jun 20, 2026
06:10
Encapsulated Cell Technology for the Delivery of Biologics to the Mouse Eye
Published on: March 30, 2020
Three-layered microcapsules as a long-term sustained release injection preparation.
Yukako Ito1, Yuya Ochii, Keizo Fukushima
1Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan. yukako@mb.kyotophu.ac.jp
International Journal of Pharmaceutics
|September 29, 2009
Summary
Three-layered milli-capsules (3LMC) offer long-term subcutaneous drug delivery. Optimizing the poly-(epsilon-caprolactone) surface membrane with Tween60 enables sustained release of low molecular weight drugs like leuprolide acetate for up to 14 weeks.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Polymer Chemistry
Background:
- Subcutaneous drug administration requires formulations for sustained release.
- Three-layered milli-capsules (3LMC) offer a potential platform for controlled drug delivery.
- Poly-(epsilon-caprolactone) (PCL) and poly(lactic acid) (PLA) are biocompatible polymers often used in drug delivery.
Purpose of the Study:
- To design and evaluate three-layered milli-capsules (3LMC) for long-term subcutaneous drug administration.
- To investigate the effect of surface membrane composition on drug release kinetics.
- To assess the in vivo performance of 3LMC for sustained delivery of leuprolide acetate.
Main Methods:
- 3LMCs were fabricated using sequential dispensing of polymer solutions.
- Poly-(epsilon-caprolactone) (PCL70) with varying concentrations of polysorbate 60 (Tween60) was used for the surface membrane.
- In vitro release studies were conducted using fluorescein isothiocyanate labeled dextrans (FD-4, FD-20) and leuprolide acetate.
- In vivo studies involved subcutaneous administration of leuprolide acetate-loaded 3LMC to rats and plasma concentration monitoring.
Main Results:
- Increasing Tween60 concentration in the PCL70 surface membrane enhanced the release rate of FD-4.
- A PCL70 surface membrane with 0.3% Tween60 demonstrated sustained release of FD-4 for 5 weeks (50.3%).
- 3LMC successfully achieved sustained release of leuprolide acetate for 5 weeks (63.0%) in vitro and maintained effective plasma concentrations for 14 weeks in rats.
- Surface membrane composition significantly impacted drug release, with specific PCL/PLA blends showing improved sustained release.
Conclusions:
- Three-layered milli-capsules (3LMC) are a viable formulation for long-term subcutaneous drug delivery.
- The surface membrane composition, particularly the inclusion of plasticizers like Tween60 and polymer blends, is critical for controlling drug release kinetics.
- 3LMC technology holds promise for developing sustained release formulations for therapeutic peptides and proteins.
Related Concept Videos
01:19Modified-Release Drug Delivery Systems: Rate-Programmed II
Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
01:26Oral Drug Delivery Systems: Continuous-Release Systems
Continuous-release drug delivery systems offer a strategic approach to maintaining therapeutic drug levels over extended periods following oral administration. By modulating the release rate of active pharmaceutical ingredients, these systems minimize fluctuations in plasma concentrations, which enhances clinical efficacy and reduces the need for frequent dosing. Such characteristics make them particularly advantageous in managing chronic diseases where patient adherence and stable drug...
01:11Oral Drug Delivery Systems: Delayed-Release Systems
Delayed-release drug delivery systems are specialized pharmaceutical formulations designed to postpone the release of active compounds until the drug reaches a specific region of the gastrointestinal (GI) tract, typically the intestine. These systems are essential for drugs that may cause gastric irritation, are unstable in acidic environments, or need to exert therapeutic effects locally in the intestinal or colonic regions.The core feature of delayed-release systems is the use of enteric...
01:22Modified-Release Drug Delivery Systems: Drug Release Characteristics
Drug release from modified-release dosage forms is designed to achieve specific therapeutic effects by controlling the rate and extent of drug release. The classification of these drug release systems is based on key pharmacokinetic assumptions: drug disposition follows first-order kinetics, drug release is the rate-limiting step in absorption, and the released drug is rapidly and completely absorbed.There are four major models of drug release patterns. The first model is the slow zero-order...
01:19Modified-Release Drug Delivery Systems: Overview
Modified-release dosage forms are designed to address the limitations of drugs with short biological half-lives. These forms maintain stable therapeutic drug concentrations over extended periods, reducing the need for frequent dosing. A consistent drug level helps minimize peak-trough fluctuations, which can reduce adverse effects, lower the risk of drug resistance, and improve overall treatment effectiveness.One common type of modified-release form is the extended-release (ER) formulation. ER...
01:22Modified-Release Drug Delivery Systems: Rate-Programmed I
Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...