Effect of micro- and nanoparticle shape on biological processes.

In the drug delivery field, there is beyond doubt that the shape of micro- and nanoparticles (M&NPs) critically affects their biological fate. Herein, following an introduction describing recent technological advances for designing nonspherical M&NPs, we highlight the role of particle shape in cell capture, subcellular distribution, intracellular drug delivery, and cytotoxicity. Then, we discuss theoretical approaches for understanding the effect of particle shape on internalization by the cell membrane. Subsequently, recent advances on shape-dependent behaviors of M&NPs in the systemic circulation are detailed. In particular, the interaction of M&NPs with blood proteins, biodistribution, and circulation under flow conditions are analyzed. Finally, the hurdles and future directions for developing nonspherical M&NPs are underscored.

Advances in the treatment of inflammatory bowel disease: Focus on polysaccharide nanoparticulate drug delivery systems.

The complex pathogenesis of inflammatory bowel disease (IBD) explains the several hurdles for finding an efficient approach to cure it. Nowadays, therapeutic protocols aim to reduce inflammation during the hot phase or maintain remission during the cold phase. Nonetheless, these drugs suffer from severe side effects or poor efficacy due to low bioavailability in the inflamed region of the intestinal tract. New protocols based on antibodies that target proinflammatory cytokines are clinically relevant. However, besides being expensive, their use is associated with a primary nonresponse or a loss of response following a long administration period. Accordingly, many researchers exploited the physiological changes of the mucosal barrier for designing nanoparticulate drug delivery systems to target inflamed tissues. Others exploited biocompatibility and relative affordability of polysaccharides to test their intrinsic anti-inflammatory and healing properties in IBD models. This critical review updates state of the art on advances in IBD treatment. Data on using polysaccharide nanoparticulate drug delivery systems for IBD treatment are reviewed and discussed.

Role of the interactions of soft hyaluronan nanomaterials with CD44 and supported bilayer membranes in the cellular uptake.

Increasing valence by acting on nanomaterial morphology can enhance the ability of a ligand to specifically bind to targeted cells. Herein, we investigated cell internalization of soft hyaluronic acid (HA) nanoplatelets (NPs) that exhibit a typical hexagonal shape, flat surfaces and high aspect ratio (Γ≈12 to 20), as characterized by atomic force microscopy in hydrated conditions. Fluorescence imaging revealed that internalization of HA-NPs by a T24 tumor cell line and by macrophages was higher than native polysaccharide in a dose-dependent and time-dependent manners. The ability of HA-NPs to efficiently compete with native HA assessed using Bio-layer interferometry showed that NPs had a stronger interaction with recombinant CD44 receptor compared to native HA. The results were discussed regarding physical properties of the NPs and the implication of multivalent interactions in HA binding to CD44. Experiments conducted on supported bilayer membranes with different compositions showed that non-specific interactions of NPs with lipid membranes were negligible. Our findings provide insights into intracellular drug delivery using soft HA-NPs through receptor-mediated multivalent interactions.

A comprehensive insight on ocular pharmacokinetics.

The eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment models of ocular drug delivery have been developed for describing the absorption, distribution, and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems, and routes of administration is discussed including factors affecting intraocular bioavailability. Factors such as precorneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, and drug metabolism render ocular delivery challenging and are elaborated in this manuscript. Several compartment models are discussed; these are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and are summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations.