Materials Science and Engineering: C2021ResearchDrug Delivery

Microfluidic preparation of PLGA composite microspheres with mesoporous silica nanoparticles for finely manipulated drug release

Jiayu Zhou, Yishu Zhai, Jumei Xu, Tian Zhou, Lian Cen29 September 2026DOI 10.1016/j.msec.2020.111917

Summary

PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs. MSNs: Average size 119 nm; specific surface area 902.53 m²/g; pore volume 1.15 cm³/g; mean pore diameter 5.09 nm; maximum RB loading ~110 mg/g. - MSN-RB release: ~95% cumulative release within 56 h; Korsmeyer–Peppas n =.

Keywords

PLGANanoparticlesSilica nanoparticlesPolymericMicrofluidicsNanocarriersGene delivery

Purpose: PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs.

Hypothesis: If mesoporous silica nanoparticles (MSNs) are incorporated into PLGA microspheres via a capillary-based three-phase microfluidic device, then the composite microspheres will acquire a denser outer PLGA layer and a more centralized porous/hollow core, enabling sustained, finely manipulated drug release without observable burst release compared with pristine PLGA microspheres.

Aims: Primary aim: Prepare PLGA composite microspheres incorporating MSNs (PLGA-MSNs) using a capillary-based three-phase microfluidic device.

Secondary aim 1: Synthesize and characterize MSNs (size, pore structure, surface area, pore volume, drug loading capability).

Secondary aim 2: Compare drug loading and in vitro release behavior of PLGA-MSNs versus pristine PLGA microspheres using rhodamine B (RB) as a water-soluble model drug.

Secondary aim 3: Investigate morphology, internal structure, encapsulation efficiency, drug loading, and release kinetics.

Delivery system:

Component: Polymer; Description: PLGA (50:50 lactide:glycolide)

Component: Microsphere Type; Description: PLGA composite microspheres incorporating mesoporous silica nanoparticles (MSNs)

Component: Fabrication; Description: Capillary-based three-phase microfluidic device generating W/O/W double emulsion

Component: Inner Phase; Description: Aqueous MSN solution (or RB solution for PLGA-RB)

Component: Middle Phase; Description: PLGA in dichloromethane (DCM, 0.6 wt%)

Component: Outer Phase; Description: PVA aqueous solution (2 wt%)

Component: Flow Rates; Description: Inner 1 mL/h, middle 2 mL/h, outer 4 mL/h

Component: MSNs; Description: Hydrothermal synthesis; average size ~119 nm; pore size ~5 nm; specific surface area ~902.5 m²/g; pore volume 1.15 cm³/g

Component: Model Drug; Description: Rhodamine B (RB), water-soluble

Component: Targeting Ligand; Description: None

Component: Microsphere Size; Description: Mean ~56 µm; CV 4.91%

Component: Key Feature; Description: MSNs act as Pickering emulsifiers, stabilizing the inner water/oil interface and producing a denser outer PLGA shell with centralized porous core

Approach: In vitro only: No cell or animal studies. - Model drug: Rhodamine B (RB) as water-soluble model drug. - Groups compared: PLGA-MSNs vs pristine PLGA microspheres. - Drug loading: MSNs impregnated with RB solutions at different concentrations; PLGA-MSNs and PLGA microspheres loaded with RB. - Release study: PBS pH 7.4 + 0.1% Tween 80 at 37°C, up to 120 days; n = 3. - Characterization: Morphology, size distribution, internal structure, encapsulation efficiency, drug loading, release kinetics.

Key methods:

Technique: FT-IR; Purpose: Confirm CTAB removal from MSNs

Technique: XRD; Purpose: Verify mesoporous structure

Technique: Nitrogen adsorption–desorption (BET/BJH); Purpose: Specific surface area, pore volume, pore size distribution

Technique: FESEM and TEM; Purpose: MSN and microsphere morphology, internal pore structure

Technique: Optical microscopy; Purpose: Emulsion droplet size distribution

Technique: CLSM; Purpose: RB distribution within microspheres

Technique: EDS; Purpose: Silicon mapping to confirm MSN distribution

Technique: UV-Vis at 554 nm; Purpose: Quantify RB loading and release

Technique: Kinetic models; Purpose: Zero-order, first-order, Higuchi, Korsmeyer–Peppas fitting

Technique: ANOVA / t-test; Purpose: Statistical significance

Key results: MSNs: Average size 119 nm; specific surface area 902.53 m²/g; pore volume 1.15 cm³/g; mean pore diameter 5.09 nm; maximum RB loading ~110 mg/g. - MSN-RB release: ~95% cumulative release within 56 h; Korsmeyer–Peppas n = 0.252, indicating Fickian diffusion. - Microsphere size: PLGA-MSN emulsion droplets 245 µm (CV 2.10%); final PLGA-MSNs 56 µm (CV 4.91%). - Encapsulation efficiency and loading: PLGA-MSNs EE 87.27–88.94%, DL 0.62–0.99%; PLGA EE 94.67–95.76%, DL 0.67–1.07%. - Release behavior: PLGA-MSNs showed sustained release for ~4 months without observable burst; cumulative release ~66.25% at 92 days and ~96% at 120 days. PLGA microspheres showed mid-term burst release: ~21.5% at 50 days, rapidly increasing to ~83% by 70 days, then ~97% at final. - Release kinetics: Korsmeyer–Peppas model best fit; n = 1.541 for PLGA-MSNs vs 1.067 for PLGA, indicating stronger skeleton erosion for PLGA-MSNs. - Internal structure: PLGA-MSNs had denser outer PLGA layer and centralized hollow/porous core; outer/inner diameter ratios 3.35–3.44 vs 1.25–1.40 for PLGA.

Interpretation: The authors conclude that incorporating MSNs into PLGA microspheres via microfluidics is an efficient strategy to finely tune drug release behavior, eliminate mid-term burst release, and achieve long-term uniform release. MSNs likely act as Pickering emulsifiers, stabilizing the inner interface and altering the microsphere core–shell structure. This platform may be useful for controlled delivery of water-soluble drugs.

Limitations: No in vivo or cell-based efficacy, toxicity, or biocompatibility studies. - Only a water-soluble model drug (RB) was tested; hydrophobic drug encapsulation and release were not evaluated. - The effect of varying MSN amounts and the fate/functionality of MSNs after release remain to be explored. - The time course of MSN elimination and microsphere morphological changes during degradation was not fully investigated. - Encapsulation efficiency of PLGA-MSNs was lower than PLGA, possibly due to incomplete RB desorption from MSNs during measurement. - No targeting ligand; no active disease targeting. - Microfluidic scale-up and throughput were not addressed.

Biochemical Pharmacology*, Volume 173, 2020, Article 113648 DOI/

7-Ketocholesterol and 7β-Hydroxycholesterol — In Vitro and Animal Models, Biological Activities, and Toxicity-Preventing Molecules

Nature Reviews Drug Discovery

Engineering Precision Nanoparticles for Drug Delivery

Materials* (MDPI; inferred from format)

Generation of Well-Defined Micro/Nanoparticles via Advanced Manufacturing Techniques for Therapeutic Delivery

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