Development of Hybrid DSPC:DOPC:P(OEGMA950-DIPAEMA) Nanostructures: The Random Architecture of Polymeric Guest as a Key Design Parameter

Abstract

Hybrid nanoparticles have gained a lot of attention due to their advantageous properties and versatility in pharmaceutical applications. In this perspective, the formation of novel systems and the exploration of their characteristics not only from a physicochemical but also from a biophysical perspective could promote the development of new nanoplatforms with well-defined features. In the current work, lipid/copolymer bilayers were formed in different lipid to copolymer ratios and examined via differential scanning calorimetry as a preformulation study to decipher the interactions between the biomaterials, followed by nanostructure preparation by the thin-film hydration method. Physicochemical and toxicological evaluations were conducted utilizing light scattering techniques, fluorescence spectroscopy, and MTS assay. 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in different weight ratios were the chosen lipids, while a linear random copolymer with pH- and thermoresponsive properties comprised of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(diisopropylamino) ethyl methacrylate (DIPAEMA) in different ratios was used. According to our results, non-toxic hybrid nanosystems with stimuli-responsive properties were successfully formulated, and the main parameters influencing their overall performance were the hydrophilic/hydrophobic balance, lipid to polymer ratio, and more importantly the random copolymer topology. Hopefully, this investigation can promote a better understanding of the factors affecting the behavior of hybrid systems.

Deciphering the Lipid-Random Copolymer Interactions and Encoding Their Properties to Design a Hybrid System

“…33 The presence of P(OEGMA-co-LMA) copolymers in the colloidal dispersions did not bring about any specific patterns as far as the physicochemical characteristics of the hybrid systems are concerned, despite the differences in the length of the OEGMA side chain (OEGMA 950 or OEGMA 500 ) and/or the %LMA content in the copolymers (Table 1). The exceptional behavior of such a mixed system due to random copolymer architecture has been reported in our recent studies 28 and is confirmed in the current one as well. It is worth mentioning, though, that there is a decreasing trend for scattered intensity by increasing the % weight P(OEGMA-co-LMA)-1 in the hybrid nanoparticles (Table S1 and Figure 2b), which overall is proportional to the mass of the colloidal systems.…”

“…The equilibration period was 5 min. The information on the equipment that was utilized for nanoparticles’ characterization can be found in the literature …”

“…The thin film hydration protocol was used for lipid/copolymer hybrid system formation, as described in detail elsewhere . The colloidal concentration in all cases was equal to C = 5 mg/mL.…”

“…The copolymers differ in the comonomer ratio and length of the OEGMA chains. Our previous studies on lipid/copolymer systems 28 and the information that was gained guided us to select the most promising hybrid platforms for further investigation. The selection of the systems is based on thermodynamic, physicochemical, and toxicological criteria in order to encode the lipid-copolymer interactions and the crucial design parameters affecting their performance.…”

Structure-Based Evaluation of Hybrid Lipid–Polymer Nanoparticles: The Role of the Polymeric Guest

“…By combining phospholipids and block copolymers, hybrid nanoparticles can be formed in an aqueous environment. The molar ratio of the components, the molecular weight and macromolecular architecture of the block copolymer, the main transition temperature of the phospholipid, and the surface charge, accompanied by the selection of an appropriate preparation protocol, are the crucial parameters for the formation of hybrid lipid/polymer vesicles and other nanomorphologies [ 1 , 5 , 6 , 7 , 8 , 9 ]. Furthermore, spheroplexes are fabricated with hybrid PLGA-cationic lipid nanoparticles for in vitro and oral delivery of siRNA [ 10 ].…”