Purpose: Conventional drug delivery systems (DDSs) are often accompanied by systemic unwanted side effects that are mainly attributable to their nonspecific biodistribution and uncontrollable drug release characteristics. Functionalized nanomaterials, particularly, polymeric nanoparticles (NPs) can increase the target specificity and accumulation, drug release control, and real time monitoring with the goal being to diminish unwanted side effects and their severity, achieving a cheaper and a generally more efficient treatment by considering more than one drug in combination therapy. Furthermore, drugs of these carriers are protected from a wide range of factors (physical and chemical changes in the body, pH changes, ionic strength, enzymatic activity, etc.). Regarding to nanosystems, they must fulfill some characteristics to be successful and able to scale up in the market, such as to have an excellent effect, which relies on the structure and formulation, with minimized toxicity (small size, and spherical shape), null or a positive electrical charge, surface functionalized, biocompatibility, and/or controlled biodegradability. Tanking in account the before mentioned, it was developed, 1) a modification of nanoprecipitation method to produce pH sensitive polymeric nanoparticles by using different polymers/solvents in the organic phase and as stabilizers; 2) a modification of emulsion-diffusion method to produce nanoparticles using different solvent blends to be used with more hydrophobic polymers and drugs and; 3) Experimental designs for this last method were achieved to determine the space design in which nanoparticles can be formed.
Methods: NPs average size, polydispersity index (PdI), and Z potential analysis were determined by photon correlation spectroscopy.
Results: Interesting results were obtained in the modification of nanoprecipitation method using different PVA-D compound ratios and concentrations as stabilizers and with different blends of alcohols-polymers used as organic phases. Higher sizes and polidispersity indexes as well as unstable systems (low Z potential) were also obtained for the previous systems. Higher polidispersity indexes and sizes were also obtained when the formulations were prepared with an aqueous phase at 3 °C than at room temperature. Compound C and especially D included in the organic phases were able to decrease the size and to increase the Z potential to provide consequently better stable systems.
Similar results were found with NPs prepared by a modification of emulsion-diffusion process, the PdI decreased as particle size decreased the by increasing the polymer solubility. Microparticles with a moderated polidispersity index were obtained using the same parameters but with E (100 %) as the organic phase and when 1% (w/v) of the polymer concentration was used. This polidispersity index was improved in the systems with 0.5 % (w/v) of polymer concentration. Finally, systems magnetically stirred, using solvent blends with a partial miscible solvent and a miscible solvent in water as a organic phases (G-D (71.43: 28.57) and
E-G (75:30)) and PVA at 2% as stabilizer, produced heterogeneous particles. The homogeneity of the batch (one population with size particles below 200 nm) and polidispersity index was improved by using high shear stirring at 8000 rpm. Z potential was negative and enough high to provide stability.
Interesting results were found from several experimental designs to know the space design in which nanoparticles can be formed using a modification of emulsion-diffusion method. In general terms, smaller sizes and PdI indexes and more physical stables systems (higher Z potential) were found decreasing the ratio of the partially miscible solvent in the organic phase and using a more polar solvent in the blend of the organic phase. Using the compound I in the blend of the organic phase produced the higher sizes and PdI indexes. Contrarily, particle sizes below 1500 nm with lower polidispersity indexes were found using mixing speeds above 1500 rpm. No differences on sizes and higher PdI indexes and Z potential values were found increasing the polymer concentration. Z potential was variable but high enough to provide physical stability. No differences on size and PdI were found using different concentration of PVA. Using Poloxamer 407 as stabilizer and decreasing the ratio of the partially miscible solvent in the organic phase, smallest sizes and polidispersity indexes were obtained (around 50 nm). Higher particles sizes were obtained increasing the stabilizer P-407 concentration.
Conclusion: We provided two straightforward methods compared with the conventional ones to produce polymeric nanoparticles that can be used to in topical and transdermal pathways for cosmetic and pharmaceutical applications. Furthermore, the nanosystems produced with these methods could be used for other pathways and other applications.