Reduction in burst release after coating poly(D,L-lactide-co-glycolide) (PLGA) microparticles with a drug-free PLGA layer

Abstract

The high initial burst release of a highly water-soluble drug from poly (D,L-lactide-co-glycolide) (PLGA) microparticles prepared by the multiple emulsion (w/o/w) solvent extraction/evaporation method was reduced by coating with an additional polymeric PLGA layer. Coating with high encapsulation efficiency was performed by dispersing the core microparticles in peanut oil and subsequently in an organic polymer solution, followed by emulsification in the aqueous solution. Hardening of an additional polymeric layer occurred by oil/solvent extraction. Peanut oil was used to cover the surface of core microparticles and, therefore, reduced or prevented the rapid erosion of core microparticles surface. A low initial burst was obtained, accompanied by high encapsulation efficiency and continuous sustained release over several weeks. Reduction in burst release after coating was independent of the amount of oil. Either freshly prepared (wet) or dried (dry) core microparticles were used. A significant initial burst was reduced when ethyl acetate was used as a solvent instead of methylene chloride for polymer coating. Multiparticle encapsulation within the polymeric layer increased as the size of the core microparticles decreased (< 50 µm), resulting in lowest the initial burst. The initial burst could be controlled well by the coating level, which could be varied by varying the amount of polymer solution, used for coating.

Porous silicon oxide–PLGA composite microspheres for sustained ocular delivery of daunorubicin

“…A PLGA coating layer is known to act as an effective barrier in preventing the premature release of drugs into aqueous media [30] [34–36] [37]. In the PLGA-pSiO 2 composites of the present study, the drug-loaded pSiO 2 particles act as drug reservoirs in the core of a PLGA microsphere, and drug leaching is slowed compared with PLGA-only microspheres.…”

“…Larger aggregates of DNR cannot form in the nanoscale pores of pSiO 2 particles due to the small physical size of these pores. Burst release from PLGA microspheres is a common phenomenon [27, 34, 36, 41, 42]. The initial burst release is hard to completely eliminate but could be reduced by using larger drug molecules and increased mass fraction of PLGA [26, 27].…”

Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications

“…Therapeutic or radiosensitizing drug release during the early stages depends on the diffusion of the escaped drug from NPs (especially polymer drug-encapsulated NPs), and polymeric degradation/erosion before reaching the desired tumor sites. Therefore, initial burst release of the encapsulated drugs/agents from such NPs should be prevented or reduced [140][141][142]. The initial burst release of drug from NPs results from poor drug encapsulation and fabrication/formulation techniques (e.g., emulsion-solvent evaporation or extraction technique) [140,143].…”

“…The initial burst release of drug from NPs results from poor drug encapsulation and fabrication/formulation techniques (e.g., emulsion-solvent evaporation or extraction technique) [140,143]. Hence, there should be high drug encapsulation efficiency and the formulation parameters for making NPs should be considered [140,142], creating diffusional resistance and preventing the quick dissolution of the drug into blood circulation [141]. The physical and chemical properties of the encapsulating polymers, the solvents used, the drug types (hydrophobic or hydrophilic), and drug-polymer interactions should be taken into account during fabrication of NPs for radiosensitization in RT applications [140,143].…”

One-Step Preparation of Poly-Lactic-Co-Glycolic-Acid Microparticles to Prevent the Initial Burst Release of Encapsulated Water-Soluble Proteins

“…To date, several methods have been developed to suppress the initial burst release of APIs from PLGA-MPs, including the replacement of PLGA with different materials with slower degradation rates [8][9][10], and the coating of the MPs with cationic compounds [11][12][13][14] or water-soluble polymers [11][12][13][14][15]. Ahmed et al [16] recently reported a new method for coating PLGAMPs with PLGA. According to this method, however, the PLGA-MPs had to be dispersed in peanut oil to enable the formation of an oil layer on their surface to prevent the dissolution and aggregation of PLGA-MPs during the PLGA coating, indicating that this coating method still required a series of time-consuming steps.…”