A New Thermodynamic Model To Predict Protein Encapsulation Efficiency in Poly(lactide) Microspheres

Abstract

Entrapment efficiency in protein microencapsulation into biodegradable polymer microspheres depends on the nature of the solvents used for dissolving the polymer. In such a system, three main interactions are present, i.e., polymer-water (aqueous protein solution), polymer-solvent, and solvent-water (aqueous protein solution). These interactions are quantified by the three interaction energies, AintEp, AintE,, and AintE2, respectively. For a given polymer, Ai&, is constant, but AintEl and AintEZ vary as a function of the nature of the solvent used. In this contribution, the model protein bovine serum albumin was microencapsulated into poly(D,L-lactic acid) by spray-drying. It was demonstrated that increasing absolute values of the sum AintEl -t AintE2 leads to decreasing encapsulation efficiencies. AintE1 was estimated from the heat of dissolution of the polymer in the selected solvents and the energy of cavity formation, and Ai& from 6 d and 6, and Drago's parameters E and C. A linear fit between the sum of interaction energies, equivalent to AintEl iAintE2, and the actual microencapsulation efficiency gave a reasonable correlation with a correlation coefficient r = 0.954. This represents an acceptable correlation considering enthalpies were used to predict interaction energies. Moreover, if microencapsulation efficiency is correlated directly with AintEl (expressed by its equivalent calculated value), and the parameters a d , 6,, E, and C, instead of Aint&, an even better correlation with a multiple r = 0.9995 is observed. This rational approach in microencapsulation is of high importance as it is based on thermodynamic parameters.

Microencapsulation of essential oils with biodegradable polymeric carriers for cosmetic applications

“…This type of biodegradable polymeric carriers can be hydrolyzed in the body to form products that are easily reabsorbed or eliminated [74][75]. The adjustable physicochemical proprieties of PLA, such as swelling and biodegradation kinetics, or molecular interaction with potential embedded drugs, offer various possibilities towards the design of controlled release systems [76][77][78][79]. These properties of biodegradable polymers are strongly defined by structural features such as copolymer composition, molecular weight and nature of the chain end-groups.…”

Drug Microencapsulation by PLA/PLGA Coacervation in the Light of Thermodynamics. 1. Overview and Theoretical Considerations

“…For this reason, calculations of the interaction energies between components with unknown parameters are often based on values obtained from materials with comparable molecular structure and properties. 29 According to the aforementioned model and adapted for the present systems, the interaction energy (∆ int E) between two components (1 and 2) can be calculated as follows: δ continuous phase ) φ 1′ δ solvent + φ 3 δ coacervating agent (3) δ coacervate phase ) φ 1 δ solvent + φ 2 δ polymer 1 (4)…”

“…Alternatively, an extension of the original model of Hô 97 has recently been reported. 29 With the use of dissolution and melting enthalpy terms, of the vaporization energy term and of the cavity term, it was possible to estimate the interaction energy between polymer and solvent. Although this approach was studied in a spray-drying process, the basic information gained should also be applicable to other techniques such as coacervation.…”

“…28 Finally, a new thermodynamic model has been recently proposed to quantify drugpolymer-solvent interactions and to predict, in terms of a scale, aqueous protein encapsulation in PLA/PLGA microspheres prepared by spray-drying. 29 In this contribution (part 1), the most relevant studies on PLA/PLGA coacervation for microsphere formation will be reviewed, and various thermodynamic models likely to be helpful for better understanding this process will be discussed. In part 2, 71 experimental physicochemical data on PLA/PLGA coacervation will be presented and interpreted in thermodynamic terms.…”

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

“…[10][11][12] Further, a new thermodynamic model has also been developed to quantify drug-polymer-solvent interactions and to characterize and predict aqueous protein encapsulation into PLA/PLGA microspheres by spray-drying. 13 In this study, the process of phase separation of various types of PLA/PLGA was analyzed in some detail by establishing phase diagrams defining the various stages of phase separation and by characterizing the coacervate and continuous phases in terms of volume, composition, polymer molecular weight, and rheological behavior. Attempts were made to interpret the results in thermodynamic terms using three different thermodynamic models based on (Flory), δ (Hildebrand) and ∆ int E (Hô, 1994).…”