NMR cryoporometry characterisation studies of the relation between drug release profile and pore structural evolution of polymeric nanoparticles.
Bottom Line: PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible.For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release.Hence, the specific reasons for the effectiveness of the synthesis route, for obtaining core-coat nanoparticles with delayed release, have been elucidated.
Affiliation: Department of Chemical and Environmental Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK.Show MeSH
Mentions: The model material used was a sol–gel silica sphere, denoted G1, which has been fully described and characterised using gas sorption and mercury porosimetry previously (Perkins et al., 2010). The pore size distribution obtained from a calibrated version of the Washburn equation was found to have a modal pore size of ∼10 nm. Cryoporometry melting curves were obtained for G1 using either aCSF or pure water as the probe fluid, and the results for both are shown in Fig. 1(a). Also included in Fig. 1(a) is the melting curve for bulk aCSF alone. For samples with G1, the small step at high temperature (∼273 K) is attributed to the melting of the film of bulk liquid surrounding the pellets, while the larger step at lower temperature is attributed to melting of intra-particle fluid. From Fig. 1(a), it can be seen that melting within G1 is depressed below the bulk melting point for water of 273.15 K. The melting point depression of aCSF within G1 is ∼5 K, which, in conjunction with the known modal pore size for G1, suggests a value of kGT of 50 nm K is probably reasonably appropriate for aCSF. It is also noted that the form of the melting curve for aCSF within G1 is very similar to that for pure water, though just shifted slightly lower in temperature. However, the melting curve step for aCSF within G1 is much sharper than the melting curve step for bulk aCSF. At the lowest temperatures (below 247 K) the melting curve for bulk aCSF is relatively flat with little signal, but at about ∼250–251 K there is a pronounced step up in intensity, followed by a long slow climb in intensity with increasing temperature, before increasing much more sharply in intensity above 270 K. The melting curve for aCSF within G1 does not have this same long tail, or the same pronounced step at ∼250–251 K. The ∼250–251 K step for the bulk aCSF sample is attributed to the melting of the pocket of high salt concentration solution produced by salt exclusion. The very slight bump in the curve for aCSF and G1 at the same temperature may be due to the same salt exclusion effect within the small amount of bulk aCSF present outside the pellets themselves, the presence of which is indicated by the small step at ∼273 K for the pellet samples. In Fig. 1(b) it can be seen that the superposed differential pore size distributions derived from the cryoporometry melting curves for water and aCSF, respectively, within G1 are very similar in form.
Affiliation: Department of Chemical and Environmental Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK.