Silica particles incorporated into PLGA-based in situ-forming implants exploit the dual advantage of sustained release and particulate delivery

Eur J Pharm Biopharm. 2020 Nov;156:1-10. doi: 10.1016/j.ejpb.2020.08.020. Epub 2020 Aug 27.


Poly (lactic-co-glycolic acid) (PLGA) in situ-forming implants are well-established drug delivery systems for controlled drug release over weeks up to months. To prevent initial burst release, which is still a major issue associated with PLGA-based implants, drugs attached to particulate carriers have been encapsulated. Unfortunately, former studies only investigated the resulting release of the soluble drugs and hence missed the potential offered by particulate drug release. In this study, we developed a system capable of releasing functional drug-carrying particles over a prolonged time. First, we evaluated the feasibility of our approach by encapsulating silica particles of different sizes (500 nm and 1 μm) and surface properties (OH or NH2 groups) into in situ-forming PLGA implants. In this way, we achieved sustained release of particles over periods ranging from 30 to 70 days. OH-carrying particles were released much more quickly when compared to NH2-modified particles. We demonstrated that the underlying release mechanisms involve size-dependent diffusion and polymer-particle interactions. Second, particles that carried covalently-attached ovalbumin (OVA) on their surfaces were incorporated into the implant. We demonstrated that OVA was released in association with the particles as functional entities over a period of 30 days. The released particle-drug conjugates maintained their colloidal stability and were efficiently taken up by antigen presenting cells. This system consisting of particles incorporated into PLGA-based in situ-forming implants offers the dual advantage of sustained and particulate release of drugs as a functional unit and has potential for future use in many applications, particularly in single-dose vaccines.

Keywords: Controlled release; Delivery system; In situ-forming implants; PLGA; Particle release.

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemical synthesis
  • Delayed-Action Preparations / pharmacokinetics
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemical synthesis
  • Drug Carriers / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Drug Implants / administration & dosage
  • Drug Implants / chemical synthesis
  • Drug Implants / pharmacokinetics*
  • Drug Liberation* / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / administration & dosage
  • Ovalbumin / chemical synthesis
  • Ovalbumin / pharmacokinetics
  • Particle Size*
  • Polylactic Acid-Polyglycolic Acid Copolymer / administration & dosage
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemical synthesis
  • Polylactic Acid-Polyglycolic Acid Copolymer / pharmacokinetics*
  • Silicon Dioxide / administration & dosage
  • Silicon Dioxide / chemical synthesis
  • Silicon Dioxide / pharmacokinetics*


  • Delayed-Action Preparations
  • Drug Carriers
  • Drug Implants
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Silicon Dioxide
  • Ovalbumin