ABSTRACT
Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Glycerol/analogs & derivatives , Nanoparticles , Polyesters , Polymers , Wireless Technology , Humans , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Polyesters/chemistry , Curcumin/administration & dosage , Curcumin/chemistry , Glycerol/chemistry , Male , Prostatic Neoplasms/therapy , Antineoplastic Agents/administration & dosage , Decanoates/chemistry , Nanofibers/chemistry , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Cell Line, Tumor , Electric Stimulation/instrumentation , Electric Stimulation/methodsABSTRACT
An electro-chemo-responsive carrier has been engineered for the controlled release of a highly hydrophilic anticancer peptide, CR(NMe)EKA (Cys-Arg- N-methyl-Glu-Lys-Ala). Remotely controlled on demand release of CR(NMe)EKA, loaded in electro-responsive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, has been achieved by applying electrical stimuli consisting of constant positive (+0.50 V) or negative voltages (-0.50 V) at pre-defined time intervals. In addition, after loading CR(NMe)EKA/PEDOT nanoparticles into an injectable pH responsive hydrogel formed by phenylboronic acid grafted to chitosan (PBA-CS), the efficiency of the controlled peptide release has increased approximately by a factor of 2.6. The hydration ratio of such hydrogel is significantly lower in acidic environments than in neutral and basic media, which has been attributed to the dissociation of the boronate bonds between polymer chains. Hence, the electro-controlled peptide release from PBA-CS/CR(NMe)EKA/PEDOT hydrogels, in the acidic environment of tumors, combines the effects of the oxidation and reduction of PEDOT chains on the interactions with the peptide and the carrier, with the peptide concentration gradient at the interface between the collapsed hydrogel and the release medium. Furthermore, the peptide released by electro-stimulation preserved its bioactivity assessed by promoting human prostate cancer cells death. Overall, this work is a promising attempt to develop a carrier platform for small hydrophilic anticancer peptides, which delivery rationale is synergistically regulated by the electrical and pH responsiveness of the carrier.
Subject(s)
Antineoplastic Agents , Bridged Bicyclo Compounds, Heterocyclic , Hydrogels , Nanoparticles , Polymers , Humans , Hydrogen-Ion Concentration , Nanoparticles/chemistry , Hydrogels/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Bridged Bicyclo Compounds, Heterocyclic/pharmacokinetics , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Polymers/chemistry , Peptides/chemistry , Delayed-Action Preparations/chemistry , Prostatic Neoplasms/drug therapy , Chitosan/chemistry , Male , Drug Delivery Systems/methodsABSTRACT
Analisa-se a relação entre práticas de gestão de recursos humanos (PGRH) e resultados organizacionais, a qual tem suscitado o interesse nas comunidades acadêmica e empresarial ao longo de várias décadas. Essa questão tem sido objeto de pesquisa em vários setores da atividade econômica em diversas regiões e países. Os resultados obtidos nesses estudos evidenciaram que o sucesso empresarial está relacionado com a forma como as empresas gerem as pessoas que nelas trabalham. Com base em uma análise de estudos publicados em diversas revistas internacionais nas duas últimas décadas, entre outras na Academy of Management Journal, salientamos as controvérsias teóricas e metodológicas que envolvem essa problemática, bem como as questões em aberto e as tendências da investigação. Sugerimos a adoção de enquadramentos teóricos multidisciplinares para explicar a relação entre PGRH e resultados organizacionais, o recurso e as metodologias qualitativas que permitam recolher informação sobre as PGRH de forma aprofundada. Sugerimos também que é conveniente pesquisar a possível existência de PGRH diferenciadas, no interior da empresa, para grupos funcionais distintos. Propomos ainda um conjunto de indicadores que podem ser utilizados no estudo sistemático das práticas de gestão de recursos humanos de elevado desempenho.
This article examines the impact of human resource management (HRM) practices on organizational performance, which in recent years has seen considerable amounts of research conducted in a number of business sectors in various regions and countries. In general, the studies conclude that there is a positive relationship between the quality of HRM practices and organizational performance. Based on empirical works on this issue, published in a variety of international journals in the last two decades, we analyze the theoretical and methodological controversy, open issues, and future research directions. We suggest: considering multidisciplinary approaches to explain the relationship between high-performance HRM practices and organizational performance; the adoption of qualitative methodologies in order to deepen our understanding of HRM practices in organizations; collecting different HRM data for distinct job groups within the same organization. We also suggest a scale that may be used for a systematic analysis of high-performance human resource management practices.