ABSTRACT
Drug delivery carriers are considered an encouraging approach for the localized treatment of disease with minimum effect on the surrounding tissue. Particularly, layer-by-layer releasing particles have gained increasing interest for their ability to develop multifunctional systems able to control the release of one or more therapeutical drugs and biomolecules. Although experimental methods can offer the opportunity to establish cause and effect relationships, the data collection can be excessively expensive or/and time-consuming. For a better understanding of the impact of different design conditions on the drug-kinetics and release profile, properly designed mathematical models can be greatly beneficial. In this work, we develop a continuum-scale mathematical model to evaluate the transport and release of a drug from a microparticle based on an inner core covered by a polymeric shell. The present mathematical model includes the dissolution and diffusion of the drug and accounts for a mechanism that takes into consideration the drug biomolecules entrapped into the polymeric shell. We test a sensitivity analysis to evaluate the influence of changing the model conditions on the total system behavior. To prove the effectiveness of this proposed model, we consider the specific application of antibacterial treatment and calibrate the model against the data of the release profile for an antibiotic drug, metronidazole. The results of the numerical simulation show that â¼85% of the drug is released in 230 h, and its release is characterized by two regimes where the drug dissolves, diffuses, and travels the external shell layer at a shorter time, while the drug is released from the shell to the surrounding medium at a longer time. Within the sensitivity analysis, the outer layer diffusivity is more significant than the value of diffusivity in the core, and the increase of the dissolution parameters causes an initial burst release of the drug. Finally, changing the shape of the particle to an ellipse produces an increased percentage of drugs released with an unchanged release time.
ABSTRACT
Limb regeneration is the outcome of a complex sequence of events that are mediated by interactions between cells derived from the tissues of the amputated stump. Early in regeneration, these interactions are mediated by growth factor/morphogen signaling associated with nerves and the wound epithelium. One shared property of these proregenerative signaling molecules is that their activity is dependent on interactions with sulfated glycosaminoglycans (GAGs), heparan sulfate proteoglycan (HSPG) in particular, in the extracellular matrix (ECM). We hypothesized that there are cells in the axolotl that synthesize specific HSPGs that control growth factor signaling in time and space. In this study we have identified a subpopulation of cells within the ECM of axolotl skin that express high levels of sulfated GAGs on their cell surface. These cells are dispersed in a grid-like pattern throughout the dermis as well as the loose connective tissues that surround the tissues of the limb. These cells alter their morphology during regeneration, and are candidates for being a subpopulation of connective tissue cells that function as the cells required for pattern-formation during regeneration. Given their high level of HSPG expression, their stellate morphology, and their distribution throughout the loose connective tissues, we refer to these as the positional information GRID (Groups that are Regenerative, Interspersed and Dendritic) cells. In addition, we have identified cells that stain for high levels of expression of sulfated GAGs in mouse limb connective tissue that could have an equivalent function to GRID cells in the axolotl. The identification of GRID cells may have important implications for work in the area of Regenerative Engineering.