Challenges for the Self-Assembly of Poly(Ethylene Glycol)–Poly(Lactic Acid) (PEG-PLA) into Polymersomes: Beyond the Theoretical Paradigms

Abstract

Polymersomes (PL), vesicles formed by self-assembly of amphiphilic block copolymers, have been described as promising nanosystems for drug delivery, especially of biomolecules. The film hydration method (FH) is widely used for PL preparation, however, it often requires long hydration times and commonly results in broad size distribution. In this work, we describe the challenges of the self-assembly of poly (ethylene glycol)-poly(lactic acid) (PEG-PLA) into PL by FH exploring different hydrophilic volume fraction (f) values of this copolymer, stirring times, temperatures and post-FH steps in an attempt to reduce broad size distribution of the nanostructures. We demonstrate that, alongside f value, the methods employed for hydration and post-film steps influence the PEG-PLA self-assembly into PL. With initial FH, we found high PDI values (>0.4). However, post-hydration centrifugation significantly reduced PDI to 0.280. Moreover, extrusion at higher concentrations resulted in further improvement of the monodispersity of the samples and narrow size distribution. For PL prepared at concentration of 0.1% (m/v), extrusion resulted in the narrower size distributions corresponding to PDI values of 0.345, 0.144 and 0.081 for PEG45-PLA69, PEG114-PLA153 and PEG114-PLA180, respectively. Additionally, we demonstrated that copolymers with smaller f resulted in larger PL and, therefore, higher encapsulation efficiency (EE%) for proteins, since larger vesicles enclose larger aqueous volumes.

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

“…Another major issue associated with the ASNase nanotechnological development is the scale-up process and its inherent challenges (Paliwal et al, 2014). Several methods are available at laboratory scale to produce nanostructures for protein drug delivery, but scale up demands high efficiency, a fast and continuous process and adequate methods for thermolabile proteins like ASNase (e.g., cold homogenization process) (Paliwal et al, 2014; Pachioni-Vasconcelos et al, 2016; Apolinário et al, 2018). Furthermore, solvent free processes and reduced shear stress are preferable to avoid ASNase denaturation and/or aggregation.…”

“…Furthermore, solvent free processes and reduced shear stress are preferable to avoid ASNase denaturation and/or aggregation. Lack of control of nanocarrier size and polydispersity are two common pitfalls for some of the production methods employed in small scale such as film hydration (Apolinário et al, 2018). To solve this problem, size exclusion chromatography can be added as a nanostructure purification step (Wang et al, 2010).…”

Preparation and Properties of Stereocomplex of Poly(lactic acid) and Its Amphiphilic Copolymers Containing Glucose Groups

“…Figure 7 is the TEM photograph of sc-PLAG-5%, and other sc-PLAG samples also possessed similar morphology. The microspheres with a diameter of about 200 nm and the aggregation of microspheres could be observed [43]. In sc-PLAG, the formation of microspheres could be induced by the stereocomplexation of enantiomeric PLA units and the amphiphilicity due to glucose residues and lactic acid units, which indicated that the hydrophobic PLA units likely spontaneously gathered in the center of microspheres to form The results of POM showed that a proper amount of glucose groups would play the role of heterogeneous nucleation agent and improve the crystallization rate of PLA stereocomplex, while a small amount or an excess glucose group could destroy the ordered arrangement of lactic acid units to reduce the regularity of SC.…”

Abrindo a Caixa De Pandora Dos Nanomedicamentos: Há Realmente Muito Mais ‘Espaço Lá Embaixo

“…Para copolímeros com porção hidrofílica formada por PEG, pode--se ainda inferir o tipo de nanoestrutura formada a partir do parâmetro f (0 < f < 1) e que representa o volume da fração hidrofílica, como descrito na Tabela 2 adaptada de Apolinário et al 41 Os polimerossomas (Figura 4) são elaborados pelos mesmos métodos usados para elaboração de lipossomas na maioria das vezes, mas em razão das características físico-químicas diferenciadas de alguns polímeros, como alta temperatura de transição vítrea que dificulta a extrusão, 42 apresentam algumas limitações, como trabalhos que relatam tempo de hidratação do filme de um mês para que ocorra a formação destas vesículas. 43 Às vezes, há a necessidade de técnicas específicas para encapsulação, como a eletroporação descrita por Wang et al, 44 que consiste na formação provisória de poros na bicamada destas vesículas, permitindo a encapsulação de moléculas grandes, como proteínas terapêuticas.…”