Polymer degradation and in vitro release of a model protein from poly(D,L-lactide-co-glycolide) nano- and microparticles

Jayanth Panyam, Manisha M. Dali, Sanjeeb K. Sahoo, Wenxue Ma, Sudhir S. Chakravarthi, Gordon L. Amidon, Robert J. Levy, Vinod Labhasetwar

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388 Scopus citations


The objective of the study was to investigate the effect of particle size of nano- and microparticles formulated from poly(D,L-lactide-co-glycolide) (50:50 PLGA) on polymer degradation and protein release. Since the surface area to volume ratio is inversely proportional to the particle size, it is hypothesized that the particle size would influence the polymer degradation as well as the release of the encapsulated protein. PLGA nano- and microparticles of approximate mean diameters of 0.1, 1 and 10 μm, containing bovine serum albumin as a model protein, were formulated using a multiple water-in-oil-in-water emulsion solvent evaporation technique. These particles were incubated at 37°C in phosphate-buffered saline (pH 7.4, 154 mM) and the particles were characterized at various time points for molecular weight of polymer, surface-associated polyvinyl alcohol content (PVA), and the particle surface topology using scanning electron microscopy. The supernatants from the above study were analyzed for the released protein and PVA content. Polymer degradation was found to be biphasic in both nano- and microparticles, with an initial rapid degradation for 20-30 days followed by a slower degradation phase. The 0.1 μm diameter nanoparticles demonstrated relatively higher polymer degradation rate (P<0.05) during the initial phase as compared to the larger size microparticles (first order degradation rate constants of 0.028 day -1, 0.011 day-1 and 0.018 day-1 for 0.1, 1 and 10 μm particles, respectively), however the degradation rates were almost similar (0.008 to 0.009 day-1) for all size particles during the later phase. All size particles maintained their structural integrity during the initial degradation phase; however, this was followed by pore formation, deformation and fusion of particles during the slow degradation phase. Protein release from 0.1 and 1 μm particles was greater than that from 10 μm size particles. In conclusion, the polymer degradation rates in vitro were not substantially different for different size particles despite a 10- and 100-fold greater surface area to volume ratio for 0.1 μm size nanoparticles as compared to 1 and 10 μm size microparticles, respectively. Relatively higher amounts of the surface-associated PVA found in the smaller-size nanoparticles (0.1 μm) as compared to the larger-size microparticles could explain some of the observed degradation results with different size particles.

Original languageEnglish (US)
Pages (from-to)173-187
Number of pages15
JournalJournal of Controlled Release
Issue number1-2
StatePublished - Sep 19 2003


  • Biodegradable polymers
  • Drug delivery
  • Particle size
  • Polyvinyl alcohol
  • Sustained release

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