A Multioptimization Approach to Assessment of Drug Delivery of PLGA Nanoparticles: Simultaneous Control of Particle Size and Release Behavior

Abstract

A multiple optimization strategy was implemented on the experimental data obtained in this study to assess drug-delivery behavior of poly(D,L-lactide-co-glycolide) (PLGA) particles. Albumin-fluorescein isothiocyanate conjugate (FITC-albumin)-loaded PLGA micro-and nanoparticles were prepared by water-in-oil-in-water double emulsion method. The experiments were carried out based on L8 Taguchi design where the effects of PLGA molecular weight, PLGA concentration in the oil phase, and sonication rate in the second emulsification step of preparation process on particle size and percentage of initial burst release of PLGA were discussed. Multioptimization toward PLGA particle size and initial burst elucidated that all aforementioned variables affect the characteristics of PLGA particles, but PLGA molecular weight was appeared as the most significant factor among studied variables. Multifarious optimizations were tested and executed varying the aforementioned factors to minimize both the size and percentage of initial burst of PLGA particles. The FTIR experiment of the optimal formulation showed the successful incorporation of the drug into the particles. These results enable careful selection and definition of optimal process parameters for the preparation of PLGA nanoparticles with sustained release properties. Furthermore, the methodology developed in this work introduces a useful tool to meet a drug delivery system with optimal release behavior.

Modeling and closed‐loop control of particle size and initial burst of PLGA biodegradable nanoparticles for targeted drug delivery

“…All images exhibit particles with a narrow size distribution except Figure (C), in which a few large particles are spotted. Some more images together with infrared spectra of pure and drug‐loaded PLGA and also in vitro release diagrams of this system were reported in our previous papers …”

“…PLGA particles were prepared through the water‐in‐oil‐in‐water emulsion–solvent evaporation method . The size and shape of the prepared PLGA particles were observed by scanning electron microscopy (SEM; Ultra Plus, Zeiss NTS, Oberkochen, Germany).…”

“…Many researchers used techniques known as “design of experiments” to uncover the relationship between the synthesis parameters and drug delivery behavior of particles. In a previous paper, we applied an L8 full factorial design approach to the pattern variation of PLGA particle size and PLGA initial burst in terms of molecular weight of PLGA, polymer concentration in water‐in‐oil‐in‐water double emulsion, and sonication rate . Though we modeled or optimized PLGA particle size and PLGA initial burst simultaneously by the L8 Taguchi design, the results could not be generalized to new scenarios, so this model could not reflect the real delivery behavior of PLGA nanocarriers.…”

“…In this work, a robust computer code has been written by hybridizing stochastic modeling (ANN) and optimization (genetics algorithm, GA) approaches to (1) find the pattern in the effects of PLGA molecular weight, PLGA concentration, the rate of sonication, and molecular weight of PVA as a stabilizer on PLGA particle size and release behavior and (2) find the best set of input variables that optimize both targets at the desired levels. The use of an artificial intelligence–based code developed in this work rather than the polynomial‐based optimization discussed in a previous work provides us with the possibility of learning the behavior of the process, generalizing the behavior learned to thousands of new scenarios not examined yet, and making decisions in selecting the best set of input variables needed to achieve the predetermined properties. Microscopic measurements were performed to assess predictions of PLGA size.…”

A journey across the solid state polymerization to assess the role of critical factors influencing the molecular weight of polylactic acid

“…Over the recent decades, developing and optimizing the properties of biodegradable polymers and polymer composites have become an important field of research because of considerable public concern about environmental criticisms of synthetic plastics . Biodegradable natural and synthetic polymers have been utilized for various uses such as biomedical , coating , antibacterial , and anticorrosion applications. Polylactic acid (PLA) is a biocompatible polymer known for its good features including excellent mechanical properties, transparency, and biocompatibility, which gives distinctive credit for packaging industry, biomedical devices, fire retardant composites, and agricultural application .…”