Current Medicinal Chemistry - Volume 30, Issue 12, 2023

The anti-inflammatory 5-aminosalicylic acid (5-ASA) is the main therapeutic option used to prevent and treat inflammatory bowel diseases. The upper intestinal tract performs rapid and almost complete absorption of this drug when administered orally, making local therapeutic levels of the molecule in the inflamed colonic mucosa difficult to achieve. Micro and nanoparticle systems are promising for 5-ASA incorporation because the reduced dimensions of these structures can improve the drug's pharmacodynamics and contribute to more efficient and localized therapy. Together, the association of these systems with polymers will allow the release of 5-ASA through specific targeting mechanisms to the colon, as demonstrated in the mesalazine modified-release dosage form. This review will summarize and discuss the challenges for the oral administration of 5-ASA and the different colon-specific delivery strategies using polymers.

Chitosan, the only naturally occurring polycationic polysaccharide derived from chitin, has long case been implicated in the designs of nanosystems for diverse biomedical and pharmaceutical applications owing to its exclusive biodegradability, biocompatibility, cationic property, and functional groups. Particularly, some intrinsic characteristics of chitosan equip it with high potential for facile preparation, flexible functionalization, and modification, which circumvent the defects of chitosan and account for extensive attempts in cancer therapy and theranostic. In this review, we first give a classifiable explanation of strategies in fabricating rationally-designed chitosan-based polymeric nanomaterials for cancer therapy, which are categorized by the physical, chemical, and biological intrinsic characteristics of chitosan, respectively. Specifically, examples harnessing the cationic charge of chitosan are clarified, and the accompanied pH-responsive ability functions frequently are also mentioned. Besides, strategies toward the modification of functional groups (amino and hydroxyl groups) in repeated glycosidic units of chitosan and their additional roles are also discussed here. Lastly, the biological superiority of chitosan as an adjuvant or a ligand for glycoprotein and the application of chitosan- based polymeric nanomaterials in theranostic are summarized. Altogether, this review provides a comprehensive overview of recent advances in chitosan-based polymeric nanomaterials for cancer therapy and theranostics from a brand new perspective.

Poly(ethylene glycol) (PEG) has been widely applied in the biomedical field as a gold standard. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles, also known as PEGylation, is a common method to improve the efficiency of drug delivery and pharmacokinetics in vivo. The effect of PEGylation on the in vivo fate of various formulations has been and continues to be extensively studied based on the successful PEGylation of proteins to improve in vivo circulation time and reduce immunogenicity. The PEG shell protects the particles from aggregation, immune recognition, and phagocytosis, thereby prolonging the in vivo circulation time. This article mainly describes the development background, advantages and applications of PEGylation in the field of drug delivery, its defects or development bottlenecks, and possible alternatives.

Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and, subsequently, ARDS progression in ill patients with SARS-CoV-2 infection. In this minireview, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.

In the last decade, selective modulators of type-2 cannabinoid receptor (CB2) have become a major focus to target endocannabinoid signaling in humans. Indeed, heterogeneously expressed within our body, CB2 actively regulates several physio-pathological processes, thus representing a promising target for developing specific and safe therapeutic drugs. If CB2 modulation has been extensively studied since the very beginning for the treatment of pain and inflammation, the more recent involvement of this receptor in other pathological conditions has further strengthened the pursuit of novel CB2 agonists in the last five years. Against this background, here we discuss the most recent evidence of the protective effects of CB2 against pathological conditions, emphasizing central nervous system disorders, bone and synovial diseases, and cancer. We also summarize the most recent advances in the development of CB2 agonists, focusing on the correlation between different chemical classes and diverse therapeutic applications. Data mining includes a review of the CB2 ligands disclosed in patents also released in the last five years. Finally, we discuss how the recent elucidation of CB2 tertiary structure has provided new details for the rational design of novel and more selective CB2 agonists, thus supporting innovative strategies to develop effective therapeutics. Our overview of the current knowledge on CB2 agonists provides pivotal information on the structure and function of different classes of molecules and opens possible avenues for future research.

COVID-19 is a contagious disease. Paxlovid, a combination of Nirmatrelvir and Ritonavir, was granted emergency use authorization by the United States Food and Drug Administration (FDA) for the treatment of COVID-19 on December 22, 2021. These are peptidomimetic coronavirus main protease inhibitors. Nirmatrelvir is a proline derivative. The present patent describes similar proline- like compounds, their preparation, use, pharmaceutical composition, and treatment.