ABSTRACT
The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug-drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods: We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results: Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions: Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.
ABSTRACT
Synthetic acyclic receptors, composed of two arms connected with a spacer enabling molecular recognition, have been intensively explored in host-guest chemistry in the past decades. They fall into the categories of molecular tweezers, clefts and clips, depending on the geometry allowing the recognition of various guests. The advances in synthesis and mechanistic studies have pushed them forward to pharmaceutical applications, such as neurodegenerative disorders, infectious diseases, cancer, cardiovascular disease, diabetes, etc. In this review, we provide a summary of the synthetic molecular tweezers, clefts and clips that have been reported for pharmaceutical applications. Their structures, mechanism of action as well as in vitro and in vivo results are described. Such receptors were found to selectively bind biological guests, namely, nucleic acids, sugars, amino acids and proteins enabling their use as biosensors or therapeutics. Particularly interesting are dynamic molecular tweezers which are capable of controlled motion in response to an external stimulus. They proved their utility as imaging agents or in the design of controlled release systems. Despite some issues, such as stability, cytotoxicity or biocompatibility that still need to be addressed, it is obvious that molecular tweezers, clefts and clips are promising candidates for several incurable diseases as therapeutic agents, diagnostic or delivery tools.
Subject(s)
Drug Industry , Molecular Conformation , Drug Delivery Systems , Drug Liberation , Humans , Nucleic Acids/chemistry , Trinucleotide Repeat ExpansionABSTRACT
Cystic fibrosis (CF) patients are faced with chronic bacterial infections displaying persistent resistance if not eradicated during the first stage of the disease. Nanoantibiotics for pulmonary administration, such as liposomal ciprofloxacin or amikacin, have progressed through clinics thanks to their sustained release, prolonged lung residence time, and low systemic absorption. In this work, we sought a nanoformulation of levofloxacin for the treatment of Pseudomonas aeruginosa. We prepared and compared poly(lactic acid)-grafted-poly(ethylene glycol) nanoparticles, as well as anionic and cationic liposomes for their size, charge, and encapsulation efficiency. Cationic liposomes were unable to encapsulate any drug and were subsequently considered as a control formulation. Regarding the efficiency of the nanocarrier, anionic liposomes exhibited a prolonged release over 72 h and preserved the antibacterial activity of levofloxacin against five strains of P. aeruginosa, whereas polymeric nanoparticles quickly released their entire payload and increased the minimum inhibitory concentration of levofloxacin. Thus, only anionic liposomes were considered for further preclinical development. Anionic liposomes exhibited a suitable colloidal stability in Turbiscan analysis and crossed a layer of artificial mucus in under 1 h in a Transwell setup. Despite their negative surface charge, liposomes still interacted with the P. aeruginosa membrane in a dose-response manner, as demonstrated by flow cytometry. Viability assays confirmed that anionic liposomes, loaded or not, exhibited a good safety profile on A549 epithelial cells, even at high concentrations. Finally, nebulization of anionic liposomes containing levofloxacin did not impact their colloidal stability, and the droplet size distribution was suitable for deep lung deposition, where the P. aeruginosa infection lies. Therefore, levofloxacin-loaded anionic liposomes exhibited suitable properties for the pulmonary treatment of P. aeruginosa in CF. This step-by-step study confirms the promising role of liposomes for lung administration of antibiotics, as recently seen in clinics, and fosters their development for several types of antibiotics.
