FT‐IR characterization and hydrolysis of PLA‐PEG‐PLA based copolyester hydrogels with short PLA segments and a cytocompatibility study

A series of the biodegradable copolyester hydrogels was prepared using a redox‐initiated polymerization with a constant 1:9 mole ratio of the Boltorn‐based acrylate and diacrylate triblock comacromonomers. The Boltorn® macromonomer was derived from the hyperbranched polyester Boltorn H20, which was functionalized at each terminus with poly(ethylene glycol) acrylate, and the diacrylate triblock macromonomer was poly (lactide‐b‐ethylene glycol‐b‐lactide) diacrylate. The hydrolysis of the copolyesters at pH 7.4 in a phosphate buffered saline solution at 37 °C was studied using ATR‐FTIR spectroscopy. It was found that the presence of the Boltorn, the PEG, and lactide block lengths both play vital roles in determining the structure‐property relationships in these materials. The ATR‐FTIR studies showed that with increasing lactide segment length, the rate of ester hydrolysis increased due to the increased concentration of the hydrolytically sensitive poly(lactic acid) (PLA) ester groups in the network. However, incorporation of Boltorn into the PLA‐PEG‐PLA copolymer did not significantly change the kinetic rate constant for hydrolysis of the PLA segments. The cytocompatibility of a typical one of these materials in the presence of its degradation by‐products was assessed using cultured osteoblasts from the rat. The hydrogel was degraded for 28 days and found to be cytocompatible with osteoblasts over days 23 to 28 of the hydrolysis period. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5163–5176     

Thermomechanical degradation of PLA‐based nanobiocomposite

Nanobiocomposites are a new class of biodegradable polymer materials with nanometric dispersion of inert particles in a biodegradable polymer matrix that show very interesting properties often very different from those of conventional‐ filled polymers and also biodegradability. An important issue in the applications of the biodegradable polymers is their easy degradability during processing due to the thermomechanical stress or to the presence of humidity. In this work, the thermomechanical degradation behavior of a nanobiocomposite made by a PLA‐based blend and an organomodified montmorillonite has been investigated. The degradation kinetics has been followed by means of rheological, mechanical and morphological characterization. In particular, the influence of temperature and of the presence of humidity have been considered. The presence of the nanoparticles slightly increases the thermomechanical degradation of the pure matrix and in particular with increasing time and temperature processing. In the more severe conditions, indeed, the organomodifier undergoes some slight decomposition of the organomodifier of the clay because of the Hoffmann elimination. The radicals formed through this decomposition enhance the degradation of the matrix. However, this decomposition is at the first stage, and the evolved CO₂ remains entrapped in the clay increasing the level of intercalation and causing also some exfoliation. Then the morphology of the nanobiocomposite changes because of the processing conditions. Moreover, the thermomechanical degradation remarkably increased if the materials are not pre‐dried because of the hydrolytic degradation of the biodegradable polyesters of the matrix. Copyright © 2015 John Wiley & Sons, Ltd.     

PLA‐based nanoparticles with tunable hydrophobicity and degradation kinetics

In this work, the preparation of poly(lactic acid) (PLA)‐based degradable nanoparticles (NPs) with tunable hydrophobicity and degradation kinetics via starved emulsion free‐radical polymerization is studied. The synthesis of macromonomers, constituted of a tunable number of lactic acid units functionalized with 2‐hydroxyethyl methacrylate (HEMA), has been performed via bulk ring opening polymerization (ROP) of L, L‐ lactide catalyzed with 2‐ethylhexanoic acid tin (II) salt. Macromonomers were characterized through SEC, NMR, and FTIR and are subsequently polymerized through monomer‐starved semi‐batch emulsion polymerization (MSSEP). The effect on the polymerization process of various emulsifiers on the final diameter and particle size distribution has been studied. The resulting PLA‐based NPs are characterized by a narrow size distribution and a small particle size, down to 25 nm. Finally, a degradation study of selected NPs has been carried out to verify their degradability in aqueous media. It has been demonstrated the complete degradability of these PLA‐based NPs which occurs upon the hydrolysis of the PLA pendant chains leaving poly‐HEMA chains, which, being hydrophilic causes the NPs to dissolve in the aqueous suspension. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Water‐dispersive PLA‐based materials: from reactive melt processing to properties

Melt blending of poly(l ‐lactide) (PLLA) and water‐soluble polymers was carried out through reactive melt processing with the objective to prepare water‐dispersible PLLA‐based materials. For this purpose, both polyvinyl alcohol (PVOH) and hydroxyethyl cellulose (HEC) were considered. Prior to melt blending, the preparation of plasticized PVOH and plasticized HEC was performed. The so‐obtained blends have been characterized in terms of morphology and thermomechanical properties. The morphological analysis evidenced the possibility to prepare co‐continuous PLLA/plasticized HEC blends. Nevertheless, their low melt strength did not allow producing monofilaments by melt spinning. Thus, PVOH was considered as an alternative to HEC. The results showed that using maleic anhydride‐grafted polylactide as a compatibilizer for PLLA/plasticized PVOH 40/60 (w/w) blends allowed preparing co‐continuous blends leading to tough monofilaments with high ultimate elongation. Moreover, the assessment of the water dispersiveness revealed that the monofilaments readily swelled in water and started to break up after 30 min. A full fragmentation of the monofilaments was observed within 1 hr. Copyright © 2015 John Wiley & Sons, Ltd.     

Tailoring the LCST of PNIPAAM‐b‐PLA‐b‐PNIPAAM Triblock Copolymers via Stereocomplexation

Poly(N‐isopropylacrylamide)‐block‐poly(l ‐lactic acid)‐block‐poly(N‐isopropylacrylamide) (PNIPAAM‐b‐PLLA‐b‐PNIPAAM) and PNIPAAM‐b‐PDLA‐b‐PNIPAAM triblock copolymers with varying polylactic acid (PLA) lengths are synthesized using a combination of ring‐opening polymerization and atom‐transfer radical polymerization. Results of ¹H NMR and gel permeation chromatography analyses show that the copolymers have a well‐defined triblock structure and the PLA segment lengths can be readily controlled with monomer feed ratio. Stereocomplexation between the enantiomeric PLA segments is confirmed with differential scanning calorimetry and wide‐angle X‐ray scattering. Dynamic light scattering experiments show that (1) the LCST of PNIPAAM in water could be tailored from 32 °C up to 38.5 °C by increasing the length of PLA segments and mixing copolymers of similar molecular weight with enantiomeric PLA segments to induce stereocomplexation, and (2) the LCST of each mixed copolymer system could be tailored within a 2–3 °C range of body temperature by manipulating the ratio of the enantiomeric copolymers in solution.

     

Methylated and pegylated PLA–PCL–PLA block copolymers via the chemical modification of di‐hydroxy PCL combined with the ring opening polymerization of lactide

Methylated and pegylated poly(lactide)‐block‐poly(ε‐caprolactone)‐block‐poly(lactide) copolymers, PLA–P(CL‐co‐CLCH₃)–PLA and PLA–P(CL‐co‐CLPEG)–PLA, were prepared in three steps: combining the formation of carbanion‐bearing dihydroxylated‐PCL, the coupling of iodomethane or bromoacetylated α‐hydroxyl‐ω‐methoxy‐poly(ethylene glycol) onto the carbanionic PCL, and finally the ring opening polymerization of DL ‐lactide initiated by the preformed grafted diOH‐PCL copolymers. The resulting block copolymers exhibited lower crystallinity, melting temperature, and hydrophobicity with respect to the original PCL. Degradation of the grafted copolymers was investigated in the presence of Pseudomonas cepacia lipase and compared with that of the triblock copolymer precursor. It is shown that the presence of the grafted substituents affected the enzymatic degradation of PCL segments. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4196–4205, 2005     

Thermosensitive t‐PLA‐b‐PNIPAAm tri‐armed star block copolymer nanoscale micelles for camptothecin drug release

Thermosensitive polylactide‐block‐poly(N‐isopropylacrylamide) (t‐PLA‐b‐PNIPAAm) tri‐armed star block copolymers were synthesized by atom transfer radical polymerization (ATRP) of monomer NIPAAm using t‐PLA‐Cl as macroinitiator. The synthesis of t‐PLA‐Cl was accomplished by esterification of star polylactides (t‐PLA) with 2‐chloropropionyl chloride using trimethylolpropane as a center molecule. FT‐IR, ¹H NMR, and GPC analyses confirmed that the t‐PLA‐b‐PNIPAAm star block copolymers had well‐defined structure and controlled molecular weights. The block copolymers could form core‐shell micelle nanoparticles due to their hydrophilic‐hydrophobic trait in aqueous media, and the critical micelle concentrations (CMC) were from 6.7 to 32.9 mg L^?1, depending on the system composition. The as‐prepared micelle nanoparticles showed reversible phase changes in transmittance with temperature: transparent below low critical solution temperature (LCST) and opaque above the LCST. Transmission electron microscopy (TEM) observations revealed that the micelle nanoparticles were spherical in shape with core‐shell structure. The hydrodynamic diameters of the micelle nanoparticles depended on copolymer compositions, micelle concentrations and media. MTT assays were conducted to evaluate cytotoxicity of the camptothecin‐loaded copolymer micelles. Camptothecin drug release studies showed that the copolymer micelles exhibited thermo‐triggered targeting drug release behavior, and thus had potential application values in drug controlled delivery. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4429–4439     

High‐Strain Shape Memory Behavior of PLA–PEG Multiblock Copolymers and Its Microstructural Origin

Shape memory properties of two thermoplastic multiblock copolymers composed of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) having different PEG‐segment lengths of 6 and 11 kDa were studied. The performance as a shape memory polymer at high strain level (600%) and its interrelations with shape‐programming conditions, molecular orientation, and microstructural changes are elucidated. A significant contribution of strain‐induced crystallization of PLA segments to the improvement of temporary shape fixation was evidenced upon increasing draw ratio and/or shape‐holding duration as well as programming temperature (within certain range) without largely sacrificing the shape recoverability. Series of microstructural characterizations reveal the occurrence of fibrillar‐to‐lamellar transformation upon shape recovery (at 60 °C) of the samples programmed at 40 °C, generating shish–kebab crystalline morphology. Such phenomenon is responsible for the high‐strain shape memory effect of these materials. The unprecedented formation of shish–kebab structure at such relatively low temperature (instead of the melting temperature range) in solid state observed in these copolymers as well as their high‐strain shape memory functionality would bestow the promising future for their practicability in diverse areas. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 241–256     

Design and Synthesis of Novel Pyrazole‐based Lp‐PLA2 Inhibitors

A series of novel pyrazole‐based lipoprotein‐associated phospholipase A₂ (Lp‐PLA₂) inhibitors have been designed and synthetized by a variety of acetophenones via a 10‐step convergent approach. The synthetic approach is carefully optimized, and an unsuccessful alternative route is also discussed. The in vitro biological activity reveals that all the synthesized compounds are potent Lp‐PLA₂ inhibitors with compound 13b being the most potent one (Lp‐PLA₂, IC₅₀=1.5 nmol/L).     

A feasible strategy to constructing hybrid conductive networks in PLA‐based composites modified by CNT‐d‐RGO particles and PEG for mechanical and electrical properties

Carbon nanotubes (CNTs) and reduced graphene oxide (RGO) were successfully assembled by chemical reaction to obtain CNT‐d‐RGO particles. Then, a home‐made dynamic impregnating device was used to prepare hybrid CNT‐d‐RGO/polyethylene glycol (PEG). Next, the different modifiers, including CNTs, GO, CNT‐d‐RGO, PEG, and CNT‐d‐RGO/PEG, were, respectively, added into poly‐(lactic acid) (PLA) matrix via melt‐compounding. The dispersed morphology for these different modifiers within the PLA matrix was confirmed by SEM and TEM observations. Especially, compared with the identical weight ratio of CNT‐d‐RGO, the hybrid CNT‐d‐RGO/PEG within the PLA matrix exhibited an excellent exfoliated and interconnected networks morphology. Moreover, compared with pure PLA, not only the crystallinity of all PLA‐based composites notably improved, but half‐crystallization time was also shortened. Furthermore, despite the addition of different modifiers, the crystal form of PLA‐based composites remained unchanged. Noticeably, compared with those of pure PLA, the tensile stress, strain, and modulus of PLA composite added with CNT‐d‐RGO/PEG increased by 29.4%, 4.1%, and 56.1%, respectively, and the V‐notch impact strength slightly improved. In addition, compared with pure PLA, volume resistivity of the PLA composite added with 1 wt% CNT‐d‐RGO/PEG decreased by 93.1%, and its volume conductivity increased by five orders of magnitude.     

Colloidal stability and drug incorporation aspects of micellar-like PLA–PEG nanoparticles

The drug delivery properties of a series of poly(lactic acid)–poly(ethylene glycol) (PLA–PEG) micellar-like nanoparticles have been assessed in terms of their colloidal stability and their ability to incorporate a water soluble drug. These studies have focused on a range of PLA–PEG copolymers with a fixed PEG block (5 kDa) and a varying PLA segment (3–110 kDa). In aqueous media, these copolymers formed micellar-like assemblies following precipitation from water miscible solvents. There was a controlled increase in the particle size as the molecular weight of the PLA block was increased. The characteristics of the PEG corona were also highly dependent on the PLA moiety. Copolymers with a low molecular weight PLA block (3–15 kDa) formed highly colloidally stable dispersions, with a complete PEG surface coverage. However, increasing the molecular weight of the PLA block resulted in significantly less colloidally stable nanoparticle dispersions, which flocculated in solvents that were significantly better than θ-solvents for the stabilising PEG chains. This can be attributed to a reduced PEG surface coverage and the probable presence of naked PLA ‘patches’ on the particle surface. These larger PLA–PEG nanoparticles (30:5–110:5) were found to be stabilised in the presence of serum components, which are thought to adsorb into the gaps on the particle surface and prevent flocculation. All of the dispersions were found to be stable under physiological conditions and therefore suitable for in vivo administration. A reasonable loading (3.1% w/w) of the micellar-like PLA–PEG 30:5 nanoparticles with the water soluble drug procaine hydrochloride was achieved. The incorporated drug was found to have no effect on the nanoparticle structure or recovery, which can be attributed to the micellar character of these assemblies and the presence of the stabilising PEG chains.     

Nano‐Stereocomplexation of Polylactide (PLA) Spheres by Spray Droplet Atomization

A direct, efficient, and scalable method to prepare stereocomplexed polylactide (PLA)‐based nanoparticles (NPs) is achieved. By an appropriate combination of fabrication parameters, NPs with controlled shape and crystalline morphology are obtained and even pure PLA stereocomplexes (PLASC) are successfully prepared using the spray‐drying technology. The formed particles of varying d ‐ and l ‐LA content have an average size of ≈400 nm, where the smallest size is obtained for PLA50, which has an equimolar composition of PLLA and PDLA in solution. Raman spectra of the particles show the typical shifts for PLASC in PLA50, and thermal analysis indicates the presence of pure stereocomplexation, with only one melting peak at 226 °C. Topographic images of the particles exhibit a single phase with different surface roughness in correlation with the thermal analysis. A high yield of spherically shaped particles is obtained. The results clearly provide a proficient method for achieving PLASC NPs that are expected to function as renewable materials in PLA‐based nanocomposites and potentially as more stable drug delivery carriers.

     

Controlled ring‐opening polymerization of trimethylene carbonate and access to PTMC‐PLA block copolymers mediated by well‐defined N‐heterocyclic carbene zinc alkoxides

Four novel Zinc–NHC alkyl/alkoxide/chloride complexes ( 4 , 5 , 9 and 9′ ) were readily prepared and fully characterized, including X‐ray diffraction crystallography for 5 and 9′ . The reaction of N‐methyl‐N′‐butyl imidazolium chloride ( 3.HCl ) with ZnEt₂ (2 equiv.) afforded the corresponding [(C_NHC)ZnCl(Et)] complex ( 4 ) via a protonolysis reaction, as deduced from NMR data. The alcoholysis of 4 with BnOH led to quantitative formation of the dinuclear Zn(II) alkoxide species [(C_NHC)ZnCl(OBn)]₂ ( 5 ), as confirmed by X‐ray diffraction analysis. The NMR data are in agreement with species 5 retaining its dimeric structure in solution at room temperature. The protonolysis reaction of N‐(2,6‐diisopropylphenyl)‐N′‐ethyl methyl ether imidazolium chloride ( 8.HCl ) with ZnEt₂ (2 equiv.) yielded the [(C_NHC)ZnCl(Et)] species 9 . The latter was found to be reactive with CH₂Cl₂ in solution and to cleanly convert to the corresponding Zn(II) dichloride [(C_NHC)ZnCl₂]₂ ( 9′ ), whose molecular structure was also elucidated using X‐ray diffractometry. Unlike Zn(II)–NHC alkoxide species 1 and 2 , which contain a NHC flanked with an additional N‐functional group (i.e. thioether and ether, respectively), the Zn(II) alkoxide species 5 incorporates a monodentate NHC ligand. The Zn(II) complexes 1 , 2 and 5 were tested in the ring‐opening polymerization (ROP) of trimethylene carbonate (TMC). All three species are effective initiators for the controlled ROP of trimethylene carbonate, resulting in the production of narrow disperse PTMC material. Initiator 1 (incorporating a thioether moiety) was found to perform best in the ROP of TMC. Notably, the latter also readily undergoes the sequential ROP of TMC and rac‐LA in the presence of a chain‐transfer agent, leading to well‐defined and high‐molecular‐weight PTMC/PLA block copolymers. Copyright © 2014 John Wiley & Sons, Ltd.     

Stabilization of pH‐Sensitive mPEG–PH–PLA Nanoparticles by Stereocomplexation Between Enantiomeric Polylactides

Methoxy poly(ethylene glycol)–poly(L ‐histidine)–poly(lactide) (mPEG₄₅–PH₃₀–PLA₈₂) triblock copolymers self‐assemble into nanoparticles by sterocomplexation. The properties of the stereocomplex nanoparticles including morphology, stability, and biocompatibility are investigated. The results reveal that the stereocomplexation between PLLA and PDLA segments could prevent the aggregation of the nanoparticles when the pH value is around 6.8. The mean diameter of the stereocomplex nanoparticles is stabilized at about 100 nm when the pH values are changed from 7.9 to 5.0. The cytotoxicity of the stereocomplex nanoparticles is evaluated, and the results demonstrate that the stereocomplexation could decrease the cytotoxicity of the PDLA segments.     

Comparative study of paclitaxel physically encapsulated in and chemically conjugated with PEG‐PLA

Paclitaxel‐loaded poly(ethylene glycol)‐b‐poly(l ‐lactide (LA)) (PEG‐PLA) micelles were prepared by two methods. One is physical encapsulation of paclitaxel in micelles composed of a PEG‐PLA block copolymer and the other is based on a PEG‐PLA–paclitaxel conjugate, abbreviated as “conjugate micelles”. Their physicochemical characteristics, e.g. critical micelle concentration (CMC), morphology, and micelle size distribution were then evaluated by means of fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The results show that the CMC of PEG‐PLA–paclitaxel and PEG‐PLA are 6.31 × 10^?4 and 1.78 × 10^?3 g L^?1, respectively. Both micelles assume a spherical shape with comparable diameters and have unimodal size distribution. Moreover, invitro drug delivery behavior was studied by high performance liquid chromatography (HPLC). The antitumor activity of the paclitaxel‐loaded micelles against human liver cancer H7402 cells was evaluated by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The conjugate micelles show a lower burst release during the initial stage and higher accumulative release amount of paclitaxel after a period of time while the encapsulated ones behave in the opposite way. Both the paclitaxel‐loaded micelles showed comparable anticancer efficacy with the free drug. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis,self‐assembly and adsorption of PEO–PLA block copolymers onto colloidal polystyrene

A series of amphiphilic block copolymers composed of poly(ethylene oxide) and poly(lactide) were synthesized and their solution properties studied using static and dynamic light scattering. These materials self‐assemble in aqueous media with the hydrodynamic radius increasing with increasing hydrophobic fraction in the copolymer. To ascertain the potential for use of these materials as degradable coatings in delivery applications, block copolymers of varying compositions were adsorbed onto a series of colloidal polystyrene particles with varying radii, and the thickness of the adsorbed layer was determined from changes in the hydrodynamic size. The adlayer thicknesses ranged from 3 to 14 nm with varying block copolymer compositions, and colloid radii. The trends fit well with theoretical models for adlayer thickness, with the exception of the smallest colloids. In these systems, we propose that the colloids may become encapsulated into the block copolymer assembly. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 244–252, 2008     

Screening of metal catalysts influence on the synthesis,structure, properties,and biodegradation of PLA‐PBA triblock copolymers obtained in melt

The synthesis of ABA type triblock copolymers comprising poly(1,4‐butylene adipate) macroinitiator and polylactide segments is described in this article. Acetylacetonates of various low‐toxic metals: Li, Mg, Ca, Zn, Fe, and Zr are used as catalysts. The course of polymerization, microstructure, thermal properties, and biodegradation of the copolymers obtained are analyzed based on the electronegativity of the metal used. The macroinitiator is completely incorporated into the major products, however, linear and cyclic lactide homopolymers and copolymers are present because of moisture presence and transesterification processes. The efficiency of side reactions depends on the catalyst used. The highest molar mass of copolymer is obtained with a Zr‐based catalyst. The efficacy of polylactide racemization is higher for catalysts comprising the metal of lower electronegativity. Under thermal degradation conditions the polylactide segment degrades before the macroinitiator one. The copolymers studied undergo faster biodegradation than polylactide and they can decompose in compost within 16 weeks. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1444–1456     

Functional copolymer/organo‐MMT nanoarchitectures. XIX. Nanofabrication and characterization of poly(MA‐alt‐1‐octadecene)‐g‐PLA layered silicate nanocomposites with nanoporous core–shell morphology

Novel bioengineering functional copolymer‐g‐biopolymer‐based layered silicate nanocomposites were fabricated by catalytic interlamellar bulk graft copolymerization of L‐lactic acid (LA) monomer onto alternating copolymer of maleic anhydride (MA) with 1‐octadecene as a reactive matrix polymer in the presence of preintercalated LA…organo‐MMT clay (reactive ODA‐MMT and non‐reactive DMDA‐MMT) complexes as nanofillers and tin(oct)₂ as a catalyst under vacuum at 80°C. To characterize the functional copolymer layered silicate nanocomposites and understand the mechanism of in situ processing, interfacial interactions and nanostructure formation in these nanosystems, we have utilized a combination of variuous methods such as FT‐IR spectroscopy, X‐ray diffraction (XRD), dynamic mechanical (DMA), thermal (DSC and TGA‐DTG), SEM and TEM morphology. It was found that in situ graft copolymerization occurred through the following steps: (i) esterification of anhydride units of copolymer with LA; (ii) intercalation of LA between silicate galleries; (iii) intercalation of matrix copolymer into silicate layers through in situ amidization of anhydride units with octadecyl amine intercalant; and (iv) interlamellar graft copolymerization via in situ intercalating/exfoliating processing. The main properties and observed micro‐ and nanoporous surface and internal core–shell morphology of the nanocomposites significantly depend on the origin of MMT clays and type of in situ processing (ion exchanging, amidization reaction, strong H‐bonding and self‐organized hydrophobic/hydrophilic interfacial interactions). This developed approach can be applied to a wide range of anhydride‐containing copolymers such as random, alternating and graft copolymers of MA to synthesize new generation of polymer‐g‐biopolymer silicate layered nanocomposites and nanofibers for nanoengineering and nanomedicine applications. Copyright © 2014 John Wiley & Sons, Ltd.     

Thermodynamic compatibility of actives encapsulated into PEG‐PLA nanoparticles: In Silico predictions and experimental verification

Achieving optimal solubility of active substances in polymeric carriers is of fundamental importance for a number of industrial applications, including targeted drug delivery within the growing field of nanomedicine. However, its experimental optimization using a trial‐and‐error approach is cumbersome and time‐consuming. Here, an approach based on molecular dynamics (MD) simulations and the Flory–Huggins theory is proposed for rapid prediction of thermodynamic compatibility between active species and copolymers comprising hydrophilic and hydrophobic segments. In contrast to similar methods, our approach offers high computational efficiency by employing MD simulations that avoid explicit consideration of the actual copolymer chains. The accuracy of the method is demonstrated for compatibility predictions between pyrene and nile red as model dyes as well as indomethacin as model drug and copolymers containing blocks of poly(ethylene glycol) and poly(lactic acid) in different ratios. The results of the simulations are directly verified by comparison with the observed encapsulation efficiency of nanoparticles prepared by nanoprecipitation. © 2016 Wiley Periodicals, Inc.