ABSTRACT
NOD1 is an intracellular receptor that, when activated, induces gene expression of pro-inflammatory factors promoting macrophages and neutrophils recruitment at the infection site. However, iE-DAP, the dipeptide agonist that promotes this receptor's activation, cannot permeate cell membranes. To develop a nanocarrier capable of achieving a high and prolonged activation over time, iE-DAP was encapsulated in nanoparticles (NPs) made of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The physicochemical properties, colloidal stability, encapsulation efficiency, and cellular uptake of iE-DAP-loaded PHVB NPs were analyzed. Results evidenced that physicochemical properties of iE-DAP-loaded NPs remained stable over time, and NPs were efficiently internalized into cells, a process that depends on time and concentration. Moreover, our results showed that NPs elicited a controlled cargo release in vitro, and the encapsulated agonist response was higher than its free form, suggesting the possibility of activating intracellular receptors triggering an immune response through the release of NOD1 agonist.
Subject(s)
Diaminopimelic Acid/analogs & derivatives , Nanoparticles/chemistry , Nod1 Signaling Adaptor Protein/drug effects , Animals , Cell Survival/drug effects , Chemistry, Pharmaceutical , Diaminopimelic Acid/administration & dosage , Diaminopimelic Acid/pharmacology , Dose-Response Relationship, Drug , Drug Carriers/chemistry , Drug Liberation , Drug Stability , Mice , Polyesters/chemistry , RAW 264.7 CellsABSTRACT
Patients' low adherence to medical treatment in chronic illnesses is one of the biggest public health problems. Numerous studies attend to the diverse factors associated with patient adherence. However, little research has been done to explore patients' reasons for non-compliance from their own point of view. In this article, we aim to understand patient non-adherence using dialogical self-theory and qualitative research methods. We interviewed 51 hypertensive patients to explore their anti- and pro-adherence motivations. Results show that most patients adhere and non-adhere to different aspects of treatment programs (medication, exercise, diet) according to the way they construct meaning to those activities. Also, our findings support the notion that patients' non-adherent behavior aims to preserve important values such as self-esteem, autonomy, affiliation, well-being, freedom, and health (or that more adherence is not worth the extra effort). We discuss the therapeutic relevance of empathically understanding patients' worldview and implicit beliefs.
