Drug Microencapsulation by PLA/PLGA Coacervation in the Light of Thermodynamics. 2. Parameters Determining Microsphere Formation

Abstract

Phase separation (frequently called coacervation) of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) is a classical method for drug microencapsulation. Here, attempts have been made to describe this process in the light of thermodynamics. Different PLA/PLGAs were dissolved in either dichloromethane or ethyl acetate, phase separated by addition of the coacervating agent silicone oil (PDMS), and hardened in either octamethylcyclotetrasiloxane or hexane. Various stages of phase separation were defined microscopically, and the coacervate and continuous phases characterized with respect to volume, composition, polymer molecular weight, and rheological behavior. The optimal amount of PDMS was inversely proportional to the polymer molecular weight and hydrophilicity, and a coacervate viscosity of above 5-10 Pa s was required for stable coacervate droplets. The composition and, consequently, viscosity of the coacervate and continuous phases depended on the polymer-solvent-PDMS interactions, as analyzed by the parameters chi (Flory), delta (Hildebrand), and delta(int)E (Hô). In general, the lattice model of FIory and Scott describing polymer-polymer incompatibility best explained the results. The interaction parameters and viscosity of the phases were also helpful to explain microsphere characteristics such as residual solvent and particle size. The data suggest that microsphere formation by polyester coacervation is primarily driven by molecular interactions between polymer, solvents, and coacervating agent.

Sustained release of TGF-β1 from biodegradable microparticles prepared by a new green process in CO2 medium

“…Indeed, proteins in a solid state are believed to preserve their bioactivity by considerably reducing conformational mobility in comparison to the large structural change found in the dissolved state (Castellanos et al, 2003;Griebenow and Klibanov, 1996). Thus, encapsulation methods involving no protein/water contact have emerged to ensure protein stability within PLGA microparticles such as s/o/w (Marquette et al, 2014), phase separation Thomasin et al, 1998) and other derivative methods (Al-Azzam et al, 2002;Yuan et al, 2009). In this regard, different techniques like spray-drying or spray-freeze drying have been reported in order to prepare small protein particles for subsequent encapsulation into PLGA microparticles.…”

A Practical Approach to the use of Nanoparticles for Vaccine Delivery

“…These nanoparticles, depending on the solvent, polymer type, polymer concentration, and addition of emulsifiers, can range in size from 50 to 500 nm. 28,29 Various alternative approaches for nanoparticle preparation have also been described based on emulsions, including spray drying 30 and phase separation, 31,32 however the solvent displacement method is the simplest. The solvent displacement method has clear advantages compared to the method to make microparticles because it is single phase that does not require high shear homogenization.…”

pH-Induced Coacervation in Complexes of Bovine Serum Albumin and Cationic Polyelectrolytes

“…[4][5][6] Protein-polyelectrolyte coacervation may be used to immobilize enzymes, an attractive alternative to microcapsulation, if these enzymes can be more active, selective, or stable in polyelectrolyte complexes or coacervates. [7][8][9] Thus, investigations of basic aspects of coacervation of proteinpolyelectrolyte complexes provide a foundation not only for the basic understanding of these supramolecular structures but also for their practical applications to protein-related industrial processes.…”