NGIWY-Amide: A Bioinspired Ultrashort Self-Assembled Peptide Gelator for Local Drug Delivery Applications

Fibrillar structures derived from plant or animal origin have long been a source of inspiration for the design of new biomaterials. The Asn-Gly-Ile-Trp-Tyr-NH2 (NGIWY-amide) pentapeptide, isolated from the sea cucumber Apostichopus japonicus, which spontaneously self-assembles in water to form hydrogel, pertains to this category. In this study, we evaluated this ultra-short cosmetic bioinspired peptide as vector for local drug delivery applications. Combining nuclear magnetic resonance, circular dichroism, infrared spectroscopy, X-ray diffraction, and rheological studies, the synthesized pentapeptide formed a stiff hydrogel with a high β-sheet content. Molecular dynamic simulations aligned well with scanning electron and atomic-force microscopy studies, revealing a highly filamentous structure with the fibers adopting a helical-twisted morphology. Model dye localization within the supramolecular hydrogel provided insights on the preferential distribution of hydrophobic and hydrophilic compounds in the hydrogel network. That was further depicted in the diffusion kinetics of drugs differing in their aqueous solubility and molecular weight, namely, doxorubicin hydrochloride, curcumin, and octreotide acetate, highlighting its versatility as a delivery vector of both hydrophobic and hydrophilic compounds of different molecular weight. Along with the observed cytocompatibility of the hydrogel, the NGIWY-amide pentapeptide may offer new approaches for cell growth, drug delivery, and 3D bioprinting tissue-engineering applications.

Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics

Titanium implants have always been regarded as one of the gold standard treatments for orthopedic applications, but they still face challenges such as pain, bacterial infections, insufficient osseointegration, immune rejection, and difficulty in personalizing treatment in the clinic. These challenges may lead to the patients having to undergo a painful second operation, along with increased economic burden, but the use of drugs is actively solving these problems. The use of systemic drug delivery systems through oral, intravenous, and intramuscular injection of various drugs with different pharmacological properties has effectively reduced the levels of inflammation, lowered the risk of endophytic bacterial infection, and regulated the progress of bone tumor cells, processing and regulating the balance of bone metabolism around the titanium implants. However, due to the limitations of systemic drug delivery systems—such as pharmacokinetics, and the characteristics of bone tissue in the event of different forms of trauma or disease—sometimes the expected effect cannot be achieved. Meanwhile, titanium implants loaded with drugs for local administration have gradually attracted the attention of many researchers. This article reviews the latest developments in local drug delivery systems in recent years, detailing how various types of drugs cooperate with titanium implants to enhance antibacterial, antitumor, and osseointegration effects. Additionally, we summarize the improved technology of titanium implants for drug loading and the control of drug release, along with molecular mechanisms of bone regeneration and vascularization. Finally, we lay out some future prospects in this field.

Recent Advances in the Local Drug Delivery Systems for Improvement of Anticancer Therapy

: The conventional anticancer chemotherapies not only cause serious toxic effects, but also produce resistance in tumor cells exposed to long-term therapy. Usually, the killing of metastasized cancer cells requires long-term therapy with higher drug doses, because the cancer cells develop resistance due to the induction of poly-glycoproteins (P-gps) that act as a transmembrane efflux pump to transport drugs out of the cells. During the last few decades, scientists have been exploring new anticancer drug delivery systems such as microencapsulation, hydrogels, and nanotubes to improve bioavailability, reduce drug-dose requirement, decrease multiple drug resistance, and to save normal cells as non-specific targets. Hopefully, the development of novel drug delivery vehicles (nanotubes, liposomes, supramolecules, hydrogels, and micelles) will assist to deliver drug molecules at the specific target site and reduce the undesirable side effects of anticancer therapies in humans. Nanoparticles and lipid formulations are also designed to deliver small drug payload at the desired tumor cell sites for their anticancer actions. This review will focus on the recent advances in the drug delivery systems, and their application in treating different cancer types in humans.

Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin

The tuneability of hydrogels renders them promising candidates for local drug delivery to prevent and treat local surgical site infection (SSI) while avoiding the systemic side-effects of intravenous antibiotic injections. Here, we present a newly developed gelatin methacryloyl (GelMA)-based hydrogel drug delivery system (GelMA-DDS) to locally deliver the broad-spectrum antibiotic cefazolin for SSI prophylaxis and treatment. Antibiotic doses from 3 µg to 90 µg were loaded in photocrosslinked GelMA hydrogel discs with 5 to 15% w/v polymer concentration and drug encapsulation efficiencies, mechanical properties, crosslinking and release kinetics, as well as bacterial growth inhibition were assessed. Our results demonstrate that all GelMA groups supported excellent drug encapsulation efficiencies of up to 99%. Mechanical properties of the GelMA-DDS were highly tuneable and unaffected by the loading of small to medium doses of cefazolin. The diffusive and the proteolytic in vitro drug delivery of all investigated cefazolin doses was characterized by a burst release, and the delivered cefazolin amount was directly proportional to the encapsulated dose. Accelerated enzymatic degradation of the GelMA-DDS followed zero-order kinetics and was dependent on both the cefazolin dose and GelMA concentration (3–13 h). Finally, we demonstrate that cefazolin delivered from GelMA induced a dose-dependent antibacterial efficacy against S. aureus, in both a broth and a diffusive assay. The cefazolin-loaded GelMA-DDS presented here provides a highly tuneable and easy-to-use local delivery system for the prophylaxis and treatment of SSI.