RESUMEN
One of the key principles of Industry 4.0 is the implementation of vertical integration, which considers the integration of information systems from different hierarchical levels in a company to support decision-making with real-time data flows. Companies face challenges when they want to implement vertical integration, which is not trivial due to the risks inherent to the decision stages of adoption. We investigate the main factors influencing the different stages of adoption of vertical integration to provide a clearer view of what managers should consider at each stage. We adopt a multi-case study approach based on the investigation of ten companies that followed this adoption process. We develop a framework with 22 factors deployed in the three stages of decision (knowledge, persuasion, and final decision) and three main dimensions of analysis: technology, organization, and environment. We analyze the potential tensions between these factors and show how managers should balance such factors during the decision stages.
RESUMEN
The human papillomavirus (HPV) infection, which is strongly related to cervical cancer, can be reduced by the topical application of imiquimod. Some strategies have been used to increase the adhesion and penetration of drugs through the vaginal mucosa. Two of them are the development of mucoadhesive semisolid formulations and the development of polymeric nanocarriers. In this paper, we hypothesize that the combined use of these two strategies results in a better performance of the formulation to retain imiquimod into the vaginal tissue. Aiming this, two different systems are proposed: (a) chitosan-coated poly(ε-caprolactone)-nanocapsules incorporated into hydroxyethylcellulose gel (HEC-NCimiq-chit), and (b) poly(ε-caprolactone)-nanocapsules incorporated into chitosan hydrogel (CHIT-NCimiq). These formulations were submitted to three main tests: mucoadhesivity by interaction, permeation and washability test (or retention test). We developed an integrative index that allows comparing the global performance of the proposed formulations by considering jointly the results of these three tests. Thus, when considered the integrative indexes for the formulations, our results show that CHIT-NCimiq presents the best performance for the treatment of HPV.
Asunto(s)
Aminoquinolinas/administración & dosificación , Aminoquinolinas/farmacocinética , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Quitosano/química , Nanocápsulas/química , Vagina/metabolismo , Administración Intravaginal , Animales , Línea Celular Tumoral , Celulosa/análogos & derivados , Portadores de Fármacos , Composición de Medicamentos , Femenino , Geles , Humanos , Imiquimod , Vehículos Farmacéuticos , Poliésteres , Porcinos , Adhesivos TisularesRESUMEN
The vaginal route of administration is an alternative for several treatments for either local or systemic pharmacological effects. However, the permanence of a drug in this route represents a challenge for formulation development that can be overcome by using nanoencapsulation and chitosan gel. Thus, this work aimed to evaluate the performance of chitosan hydrogels containing cationic and anionic acrylic-based nanocapsules (Eudragit RS 100 and Eudragit S 100, respectively) with Nile red as a model of lipophilic substance in the vaginal route of administration, as measured by increases in the residence time and the penetration of these formulations. Several formulations were prepared with increasing chitosan concentrations, and were analyzed in terms of pH and rheological behavior so that the most suitable formulation could be selected. The enhancement of the adhesion (tensile stress test and washability profile) and penetration (confocal laser scanning microscopy and extraction followed by quantification) properties of the formulations, when applied to porcine vaginal mucosa, were evaluated. The nanocapsule suspensions produced presented adequate properties: size of approximately 200 nm (polydispersity index of ≤0.2); zeta potential around +10 mV for the cationic formulation and -10 mV for the anionic formulation; and pH values of 6.1±0.1 (Eudragit RS 100), 5.3±0.2 (Eudragit S 100), 6.2±0.1 (Nile red loaded Eudragit RS 100), and 5.1±0.1 (Nile red loaded Eudragit S 100). The chitosan formulation presented suitable viscosity for vaginal application and acidic pH (approximately 4.5). The tensile stress test showed that both formulations containing polymeric nanocapsules presented higher mucoadhesion when compared with the formulation without nanocapsules. In the washability experiment, no significant differences were found between formulations. Confocal microscopy and fluorescence quantification after extraction from the mucosa showed higher penetration of Nile red when it was nanoencapsulated, particularly in cationic nanocapsules. The formulations developed based on chitosan gel vehicle at 2.5% weight/weight containing polymeric nanocapsules, especially the cationic nanocapsules, demonstrated applicability for the vaginal delivery of hydrophobic substances.