Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

Sci Adv. 2016 May 27;2(5):e1600519. doi: 10.1126/sciadv.1600519. eCollection 2016 May.


Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules.

Keywords: PLGA; affinity release; central nervous system; controlled release; drug delivery; hydrogel; protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Brain-Derived Neurotrophic Factor / administration & dosage
  • Brain-Derived Neurotrophic Factor / pharmacokinetics
  • Delayed-Action Preparations*
  • Drug Carriers* / chemistry
  • Drug Compounding
  • Drug Delivery Systems*
  • Drug Liberation
  • Hydrogen-Ion Concentration
  • Lactic Acid* / chemistry
  • Monte Carlo Method
  • Nanoparticles* / chemistry
  • Polyglycolic Acid* / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Proteins / administration & dosage
  • Proteins / chemistry
  • Proteins / pharmacokinetics
  • Static Electricity


  • Brain-Derived Neurotrophic Factor
  • Delayed-Action Preparations
  • Drug Carriers
  • Proteins
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid