RESUMO
The worldwide health burden of colorectal cancer is still substantial, and traditional chemotherapeutic drugs sometimes have poor selectivity, which can result in systemic toxicity and unfavorable side effects. For colon-specific medication delivery, bioengineered carbohydrate polymers have shown promise as carriers. They may enhance treatment effectiveness while minimizing systemic exposure and associated side effects. The unique properties of these manufactured or naturally occurring biopolymers, such as hyaluronic acid, chitosan, alginate, and pectin, enable targeted medicine release. These qualities can be changed to meet the physiological needs of the colon. In the context of colorectal cancer therapy, this article provides a comprehensive overview of current developments and prospective future directions in the field of bioengineered carbohydrate polymer synthesis for colon-specific drug delivery. We discuss numerous techniques for achieving colon-targeted drug release, including enzyme-sensitive polymers, pH-responsive devices, and microbiota-activated processes. To increase tumor selectivity and cellular uptake, we also examine the inclusion of active targeting approaches, such as conjugating specific ligands. Furthermore, we discuss the potential of combination treatment strategies, which use the coadministration of numerous therapeutic medications to target multiple pathways implicated in cancer growth and address drug resistance mechanisms. We address recent biomimetic advances that potentially improve the biocompatibility, cellular uptake, and tumor penetration of carbohydrate polymer-based nanocarriers. These methods involve protein corona engineering and cell membrane coating. Furthermore, we look at the possibility of intelligent and sensitive systems that may adjust their behaviors in response to certain inputs or feedback loops, allowing for precise and regulated drug distribution.
RESUMO
Since their discovery in valsartan-containing drugs, nitrosamine impurities have emerged as a significant safety problem in pharmaceutical products, prompting extensive recalls and suspensions. Valsartan, candesartan, irbesartan, olmesartan, and other sartans have been discovered to have additional nitrosamine impurities, such as N-nitroso-N-methyl-4-aminobutyric acid (NMBA), N-nitroso-Di-isopropyl amine (NDIPA), N-nitroso-Ethyl-Isopropyl amine (NEIPA), and N-nitroso-Diethyl amine (NDEA). Concerns about drug safety have grown in response to reports of nitrosamine contamination in pharmaceuticals, such as pioglitazone, rifampin, rifapentine, and varenicline. This review investigates the occurrence and impact of nitrosamine impurities in sartans and pharmaceutical goods, as well as their underlying causes. The discussion emphasizes the significance of comprehensive risk assessment and mitigation approaches at various phases of medication development and manufacturing. The link between amines and nitrosamine impurities is also investigated, with an emphasis on pH levels and the behaviour of primary, secondary, tertiary, and quaternary amines. Regulations defining standards for nitrosamine assessment and management, such as ICH Q3A-Q3E and ICH M7, are critical in resolving impurity issues. Furthermore, the Global Substance Registration System (GSRS) is underlined as being critical for information sharing and product safety in the pharmaceutical industry. The review specifically focuses on the relationship between ranitidine and N-nitroso dimethyl amine (NDMA) in the context of the implications of nitrosamine contamination on patient safety and medicine supply. The importance of regulatory authorities in discovering and correcting nitrosamine impurities is highlighted in order to improve patient safety, product quality, and life expectancy. Furthermore, the significance of ongoing study and attention to nitrosamine-related repercussions for increasing pharmaceutical safety and overall public health is emphasized.
