microfluidic-aided synthesis of poly (ℇ-caprolactone) nanoparticles containing dexamethasone: morphology, size distribution and release studies

In recent years, research projects in the field of polymeric nanoparticles (nps) for drug delivery applications are increasing promptly. dexamethasone (dex) is one of the most effective drugs in treatment of infectious diseases. besides its benefits, it has some drawbacks, such as short half-life, rapid metabolism, and poor bioavailability. to overcome these limitations, the suitable polymer nanoparticulate system can be introduced. poly (ℇ-caprolactone) (pcl) is one of the most practical polymers in drug delivery systems due to its unique features, such as great biocompatibility, biodegradability, non-immunogenicity, and high drug loading capacity along with permeability which increases the control release of the drug. in recent years, microfluidics (mf) technology has been developed in a myriad of biomedical fields, especially nanoparticle synthesis. this technology possesses great features including controlled mixing of phases, low consumption of raw materials and minimal costs. therefore, the nps have been produced with a smaller size and the narrower polydispersity index (pdi) as well as the higher encapsulation efficiency than the traditional bulk methods (bm). in this study, a novel dex-loaded pcl nps were synthesized by the use of mf-based nanoprecipitation method. first, the mf device and its microchannels were designed with autocad software and then embedded on the poly (methyl methacrylate) (pmma) plate using a co2 laser machine. next, the dex-loaded pcl nps were synthesized by bm and mf nanoprecipitation methods. regarding characterization tests, some crucial physicochemical properties, such as morphology, size, size distribution, surface charge, encapsulation efficiency (ee) and loading capacity (lc) were evaluated for nps synthesized by two methods. finally, the drug release behaviour was studied in phosphate buffer solution (pbs, ph 7.4). to explain results in detail, it is found that the nps prepared by mf showed smaller size (~67 nm) and lower polydispersity index (0.12) compared to those prepared by bulk method (bm). it is due to the dominance of the laminar flow regime with reynolds’ numbers less than 100 over turbulent flow through the microchannels leading to a homogeneous mixing between the continuous and dispersed phases. moreover, the mf-based nps have higher surface charge (-45.00±4.15 mv) because of more effective repulsive forces than attractive forces onto the surface of mf-based nps leading to more stable colloids with less agglomeration. additionally, the mf-based nps showed higher encapsulation efficiency (74.25±2.01%) and loading capacity (12.56±0.86%) due to rapid mixing, laminar flow, and adequate interaction between polymer and drug molecules, which in turn could result in higher amounts of ee and lc for mf-based nps. finally, in vitro release studies revealed that dex release from mf-based nps not only experienced a lower burst release (7% after 30 min) but also a more controlled release (80% after 48 h) compared to bm-based nps. although, the nps synthesized via mf exhibited smaller size than bm ones, the mf method was able to make high control over the nps production with remarkable compactness that led to the slower diffusion of the drug molecules from the center of nps with more controlled release profiles. additionally, the large number of small nps in the bm-based nps might also be an important factor resulting in overall faster release than mf ones. in conclusion, due to the desirable properties of mf-based nps, they can be considered as a practical drug delivery system for the controlled release of dex in biomedical applications.