Constructing a drug release model by central composite design to investigate the interaction between drugs and temperature-sensitive controlled release nanoparticles.

ABSTRACT

To study the release behavior of a thermosensitive controlled release drug delivery system and construct a predictable mathematical model of drug release, poly(N-isopropylacrylamide-co-Allylamine) (P(NIPA-AL17)) and ploy(styrene sulfonate) (PSS) were functionalized on the surface of hollow mesoporous carbon nanoparticles (HMCNs) through layer-by-layer (LBL) assembly to construct a photothermal responsive controlled release system. A five-level four-factorial central composite design (CCD) was performed to investigate the relationship between four independent variables including drug loading (A), number of polymer layers (B), temperature (C) and vibration rate of the shaker (D), and three dependent response variables, including cumulative release over 1 h (Y1), cumulative release over 24 h (Y2) and the release rate constant k (Y3). The CCD results indicate that A and C significantly affect Y1 (P < 0.05). C significantly affects Y2 (P < 0.05). A and B is found to affect Y3 (P < 0.05) significantly. When C is below 39 °C, Y1 and Y2 decrease with the increase of A and B, and when C is above 39 °C, they increase with the increase of A and B; Y3 decreases as A and B increase; and D shows the least or even no influence on Y1, Y2 and Y3. The constructed predictable mathematical model will provide a scientific reference for the further development and application of photothermal responsive controlled-release preparations.