RESUMO
Several decades of research and clinical trials have conclusively provided proof of concept on the usefulness of monoclonal antibodies in the armamentarium against cancer. There are numerous mAbs approved for both, the treatment of solid tumors as well as hematological malignancies. These have ranked in the top ten best-selling drugs in recent years and one such mAb, pembrolizumab, is slated to be the highest revenue-generating drug by 2024. A large proportion of the mAbs in oncology have been approved by regulatory agencies in just the past decade and many professionals working in the field have been unable to keep abreast with the latest mAbs available and their mechanism of action. In this review, we aim to provide a systematic compilation of the various mAbs in oncology, approved by the US FDA in the past decade. It also elaborates on the mechanism of action of the newly approved mAbs to provide an overall update of the same. For this purpose, we have referred to the Drugs at FDA and relevant articles from PubMed from the year 2010 to date.
Assuntos
Antineoplásicos Imunológicos , Neoplasias , Antineoplásicos Imunológicos/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Antígenos de Neoplasias/metabolismo , Microambiente Tumoral , Receptores de Fatores de Crescimento/antagonistas & inibidores , Antígenos CD/metabolismo , Proteínas de Checkpoint Imunológico/metabolismo , AnimaisRESUMO
Mesua ferrea Linn. is used traditionally in India and South East Asian countries as an antiseptic, antidote and a brain tonic. Recent pharmacological studies on the plant have highlighted M. ferrea to be a rich source of secondary metabolites, with proven therapeutic applications. Since the toxicity of a plant following repeated exposure is of higher clinical significance, the present investigation was conducted to establish the subacute toxicity profile of the ethanolic extract of Mesua ferrea flowers (MFE). The study was conducted in accordance with the OECD Guideline 407, wherein MFE was administered orally to groups of male and female rats (n = 5/group/sex) at the doses of 100, 500 and 1000 mg/kg, over a period of 28 days. Repeated administration of MFE had no adverse effect on the growth rate and hematological parameters of the animals. There were no changes in the biochemical parameters, except for a slight decrease in the CHOL (total cholesterol) levels, and an increase in the levels of AST (aspartate aminotransferase) and ALT (alanine aminotransferase), at the highest dose. The latter corroborated with the histopathological findings exhibiting mild lymphocytic infiltration and hepatocyte degeneration observed in the liver tissues of both sexes. According to the study, the no-observed-adverse-effect level (NOAEL) of M. ferrea in the 28-day repeated dose toxicity study in rats was 500 mg/kg. Though the overall effects of the extract at the highest dose did not translate into any serious complications, its effect on hepatic function needs to be established over a longer period of study.
Assuntos
Flores , Magnoliopsida , Extratos Vegetais , Animais , Aspartato Aminotransferases/metabolismo , Feminino , Flores/química , Fígado , Magnoliopsida/química , Masculino , Extratos Vegetais/toxicidade , Ratos , Testes de Toxicidade SubagudaRESUMO
BACKGROUND: Local delivery to bowel tissue through oral administration is a challenging but a desirable goal to treat diseases like inflammatory bowel disease (IBD). Colon specific drug delivery system should be capable of protecting the drug en route colon. PURPOSE: Liposomes have shown potential to specific accumulation at inflammation site thus reduce toxicity; hence it can be used for effective treatment of IBD. METHODS: Liposomes prepared using thin film hydration method. Statistical design was used for optimization. Colitis was induced using acetic acid. Inverted sac method was used as ex vivo model for IBD. Myeloperoxidase (MPO) activity and histopathology comparative study was carried out. Liposomes were formulated in enteric coated capsules to deliver the liposome specifically in initial segment of colon. RESULTS: Particle size and entrapment efficiency were between 200 and 300 nm and 40 and 60%, respectively. In vivo and ex vivo study indicates higher accumulation of liposomes in colonic region as compared to pure drug. Enteric coated capsules delivered the drug after 5 h lag time. DISCUSSION: Low particle size is attributed to low lipid content and stabilization due to surfactant. At higher cholesterol level, vesicles cannot reshuffle into smaller vesicles due to rigidization. Study shows higher accumulation of liposomes due to its lipoidal nature as compared to pure drug due to membrane transfer mechanism of drug thus MPO significantly lowers as compared to standard group (p < 0.05). CONCLUSIONS: Higher accumulation of liposomal drug in inflammatory area and specific release of liposomes by enteric coated capsules provide better option for the treatment of colonic disease.