Modularity of RBC hitchhiking with polymeric nanoparticles: testing the limits of non-covalent adsorption.

Red blood cell (RBC) hitchhiking has great potential in enhancing drug therapy, by improving targeting and reducing rapid clearance of nanoparticles (NPs). However, to improve the potential for clinical translation of RBC hitchhiking, a more thorough understanding of the RBC-NP interface is needed. Here, we evaluate the effects of NP surface parameters on the success and biocompatibility of NP adsorption to extracted RBCs from various species. Major differences in RBC characteristics between rabbit, mouse and human were proven to significantly impact NP adsorption outcomes. Additionally, the effects of NP design parameters, including NP hydrophobicity, zeta potential, surfactant concentration and drug encapsulation, on RBC hitchhiking are investigated. Our studies demonstrate the importance of electrostatic interactions in balancing NP adsorption success and biocompatibility. We further investigated the effect of varying the anti-coagulant used for blood storage. The results presented here offer new insights into the parameters that impact NP adsorption on RBCs that will assist researchers in experimental design choices for using RBC hitchhiking as drug delivery strategy.

Ways to Improve Insights into Clindamycin Pharmacology and Pharmacokinetics Tailored to Practice.

Given the increase in bacterial resistance and the decrease in the development of new antibiotics, the appropriate use of old antimicrobials has become even more compulsory. Clindamycin is a lincosamide antibiotic approved for adults and children as a drug of choice for systemic treatment of staphylococcal, streptococcal, and gram-positive anaerobic bacterial infections. Because of its profile and high bioavailability, it is commonly used as part of an oral multimodal alternative for prolonged parenteral antibiotic regimens, e.g., to treat bone and joint or prosthesis-related infections. Clindamycin is also frequently used for (surgical) prophylaxis in the event of beta-lactam allergy. Special populations (pediatrics, pregnant women) have altered cytochrome P450 (CYP)3A4 activity. As clindamycin is metabolized by the CYP3A4/5 enzymes to bioactive N-demethyl and sulfoxide metabolites, knowledge of the potential relevance of the drug's metabolites and disposition in special populations is of interest. Furthermore, drug-drug interactions derived from CYP3A4 inducers and inhibitors, and the data on the impact of the disease state on the CYP system, are still limited. This narrative review provides a detailed survey of the currently available literature on pharmacology and pharmacokinetics and identifies knowledge gaps (special patient population, drug-drug, and drug-disease interactions) to describe a research strategy for precision medicine.