Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.

TransfersomILs: From Ionic Liquids to a New Class of Nanovesicular Systems

Ionic liquids (ILs) have increasingly been studied as key materials to upgrade the performance of many pharmaceutical formulations. In controlled delivery systems, ILs have improved multiple physicochemical properties, showing the relevance of continuing to study their incorporation into these formulations. Transfersomes are biocompatible nanovesicular systems, quite useful in controlled delivery. They have promising characteristics, such as elasticity and deformability, making them suitable for cutaneous delivery. Nonetheless, their overall properties and performance may still be improved. Herein, new TransfersomILs systems to load rutin were developed and the physicochemical properties of the formulations were assessed. These systems were prepared based on an optimized formulation obtained from a Box–Behnken factorial design (BBD). The impact of imidazole-based ILs, cholinium-based ILs, and their combinations on the cell viability of HaCaT cells and on the solubility of rutin was initially assessed. The newly developed TransfersomILs containing rutin presented a smaller size and, in general, a higher association efficiency, loading capacity, and total amount of drug release compared to the formulation without IL. The ILs also promoted the colloidal stability of the vesicles, upgrading storage stability. Thus, ILs were a bridge to develop new TransfersomILs systems with an overall improved performance.

Advanced Hydrogels for the Controlled Delivery of Insulin

Insulin is a peptide hormone that is key to regulating physiological glucose levels. Its molecular size and susceptibility to conformational change under physiological pH make it challenging to orally administer insulin in diabetes. The most effective route for insulin delivery remains daily injection. Unfortunately, this results in poor patient compliance and increasing the risk of micro- and macro-vascular complications and thus rising morbidity and mortality rates in diabetics. The use of 3D hydrogels has been used with much interest for various biomedical applications. Hydrogels can mimic the extracellular matrix (ECM) and retain large quantities of water with tunable properties, which renders them suitable for administering a wide range of sensitive therapeutics. Several studies have demonstrated the fixation of insulin within the structural mesh of hydrogels as a bio-scaffold for the controlled delivery of insulin. This review provides a concise incursion into recent developments for the safe and effective controlled delivery of insulin using advanced hydrogel platforms with a special focus on sustained release injectable formulations. Various hydrogel platforms in terms of their methods of synthesis, properties, and unique features such as stimuli responsiveness for the treatment of Type 1 diabetes mellitus are critically appraised. Key criteria for classifying hydrogels are also outlined together with future trends in the field.

Calcium and Strontium Coordination Polymers as Controlled Delivery Systems of the Anti-Osteoporosis Drug Risedronate and the Augmenting Effect of Solubilizers

Bisphosphonates (BPs) constitute a class of drugs used for the treatment of calcium- and bone-related disorders, including osteoporosis, Paget’s disease, etc. The presence of the anionic phosphonate groups endows them with the ability to act as ligands to metal ions. As a result, the synthesis of complexes or coordination polymers of various structural motifs can be accomplished. In this work, the 3rd generation BP drug risedronate (RIS) was combined with biologically acceptable alkaline earth metal ions (e.g., Ca2+ and Sr2+) in an effort to synthesize new materials. These metal–RIS compounds can operate as controlled delivery systems (CDSs) when exposed to appropriate experimental conditions, such as the low pH of the human stomach. CDS networks containing Ca2+ or Sr2+ and RIS were physicochemically and structurally characterized and were evaluated for their ability to release the free RIS drug during an acid-driven hydrolysis process. Due to the low solubility of RIS at low pH, cationic additives (linear polyethyleneimine and amine-terminated polyaminoamide dendrimer) were utilized as drug solubilizers. Based on the drug release results of this study, there was an attempt to correlate the drug release efficiency with the structural features of these CDSs.