A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of

Novel PF74-like small molecules targeting the HIV-1 capsid protein: Balance of potency and metabolic stability

Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (

Vih-Sida: complicaciones neurológicas de los pacientes asistidos en un hospital general de adultos / HIV-AIDS: Neurological complications of patients treated in a general hospital for adults

Resumen: Arch Med Interna 2013 - 35(1):05-08 Las complicaciones neurológicas son frecuentes en los pacientes afectados por el virus de inmunodeficiencia humana (VIH). Se realizó un estudio descriptivo, retrospectivo, para conocer la frecuencia de la patología neurológica en los pacientes VIH/SIDA (síndrome de inmunodeficiencia adquirida) de nuestro centro, su perfil clínico y evolutivo, comparar el grado de inmunodepresión, el tiempo de estadía hospitalaria, la gravedad de la afección (estimada por requerimiento de ingreso a CTI) y la mortalidad entre los pacientes que se presentaban con enfermedades oportunistas (EO) y enfermedades no oportunistas (ENO). Se encontró una alta prevalencia de enfermedad neurológica (21%), en población joven, en su mayoría de sexo masculino, con inmunodepresión muy severa, predominando la etapa SIDA; las EO son las más frecuentes y registran mayor morbimortalidad que las ENO. Nuestra población no registra la transición epidemiológica del mundo desarrollado vinculado al uso de terapia antirretroviral (TARV), hecho que atribuímos a sus condiciones socio-económico-culturales.

Abstract: Arch Med Interna 2013 - 35(1):05-08 Neurological complications are common in patients with human immunodeficiency virus (HIV). We conducted a descriptive study, to determine the frequency of neurological disease in HIV/AIDS (acquired immunodeficiency syndrome) in our center, their clinical and developmental profile, and compare the degree of immunosuppression, the length of hospital stay, severity of the condition (estimated income requirement to intensive care unit [ICU]) and mortality between the patients presenting with opportunistic disease (OD) and non-opportunistic disease (NOD). High prevalence of neurological disease (21%) was found, mostly in young people, male, with severe immunosuppression, dominating the AIDS stage. ODs are more frequent and have higher recorded morbidity than NOD. Our population does not record the epidemiological transition seen in the developed world linked to the use of antiretroviral therapy (ART), a fact we attribute to the socio-economic-cultural situation.