A revolution in chemical biology occurred with the introduction of click chemistry. Click chemistry plays an important role in protein chemistry modifications, providing specific, sensitive, rapid, and easy-to-handle methods. Under physiological conditions, click chemistry often overlaps with bioorthogonal chemistry, defined as reactions that occur rapidly and selectively without interfering with biological processes. Click chemistry is used for the posttranslational modification of proteins based on covalent bond formations. With the contribution of click reactions, selective modification of proteins would be developed, representing an alternative to other technologies in preparing new proteins or enzymes for studying specific protein functions in different biological processes. Click-modified proteins have potential in diverse applications such as imaging, labeling, sensing, drug design, and enzyme technology. Due to the promising role of proteins in disease diagnosis and therapy, this review aims to highlight the growing applications of click strategies in protein chemistry over the last two decades, with a special emphasis on medicinal applications.

Epilepsy treatment requires anti-seizure medical formulations; available medications have various painful side effects and penetrate the brain–blood barrier poorly. A promising method is the use of natural clay nanocontainers for drug delivery through this membrane barrier. Halloysites (Hly) are biocompatible, 50-nm diameter tubes with a positively charged, hollow inner lumen and negatively charged outer shell and are available naturally. These characteristics enable them to be versatile as drug loaded ‘nano-torpedoes’ effectively penetrating cell membranes. The endothelial cells are a major cell type in the blood–brain barrier that provides for the selective permeability separating the circulating blood and allowing only the passage of glucose, water, and amino acids, but not traditional drug formulations. Nanotubes encapsulating rhodamine isothiocyanate and ionomycin penetration through the rat-brain microvascular endothelial cells followed by a prolonged 24-h drug release was demonstrated. A model membrane was set up across 0.4-μm-pore polystyrene transwell supports covered by seeding endothelial and astrocyte cells to mimic the blood–brain barrier in vivo. This barrier demonstrated a dual permeation mechanism (inter-cell accumulation and through-passing) for loaded Hlys, exploiting the potential of this nanoclay in the trans-membrane delivery of drugs. Use of Hly nanotubes as drug carriers to penetrate the brain microvascular endothelial barrier and to deliver the payload displayed a new approach for the treatment of brain diseases such as epilepsy.

Over the past several decades, clay minerals have been applied in various bio-fields such as drug and drug additives, animal medicine and feed additives, cosmetics, biosensors, etc. Among various research areas, however, the medical application of clay minerals is an emerging field not only in academia but also in industry. In particular, cationic and anionic clays have long been considered as drug delivery vehicles for developing advanced drug delivery systems (DDSs), which is the most important of the various research fields including new drugs and medicines, in vitro and in vivo diagnostics, implants, biocompatible materials, etc., in nanomedicine. These applications are obviously related to global issues such as improvements in welfare and quality of life with life expectancy increasing. Many scientists, therefore, in various disciplines, such as clay mineralogy, material chemistry, molecular biology, pharmacology, and medical science, have been endeavoring to find solutions to such global issues. One of the strategic approaches is probably to explore new drugs possessing intrinsic therapeutic effects or to develop advanced materials with theranostic functions. With this is mind, discussions of examples of cationic and anionic clays with bio- and medical applications based on nanomedicine are relevant. In this tutorial review, nanomedicine based on clay minerals are described in terms of synthetic strategies of clay nanohybrids, in vitro and in vivo toxicity, biocompatibility, oral and injectable medications, diagnostics, theranosis, etc.

Biocompatible drug-delivery materials are important because they provide controlled release of biologically active agents to enhance the effectiveness of medical treatments. Montmorillonite (Mnt) has been utilized in drug-delivery systems for delayed-release application because it can safely encapsulate drug molecules via intercalation reactions. The objective of the present study was to evaluate the delivery characteristics of the drug ciprofloxacin (CIP) from a composite with Mnt (Mnt-CIP) in which the Mnt was first prepared by acid treatment and vibration ball milling. The surfaces of Mnt were modified by reacting the Mnt suspension in 1.0 M HCl acid and by dispersing the powder with a vibration ball mill, then the CIP drug was added at pH 4 and stirred. The goal was to improve the sustained-release performance of the CIP. This Mnt-CIP drug-release system was characterized by X-ray diffraction, X-ray fluorescence analysis, Fourier-transform infrared spectroscopy, surface area measurement using the Brunauer-Emmett-Teller (BET) method, and ultraviolet spectroscopy. The X-ray diffraction results confirmed the intercalation of CIP into the interlayer space of Mnt. The in vitro release properties of the intercalated CIP were investigated using a simulated phosphate-buffered saline solution (pH 7.4) at 36±0.5°C. The CIP drug exhibited a continued release for 3 h. Moreover, Mnt prepared by HCl acid treatment and dispersion in the vibration ball mill delayed the drug dissolution rate. In summary, the Mnt-CIP composite prepared in this study exhibited slow and sustained release characteristics, indicating that Mnt mined from the Gampo-40 mining area in Gyeongju can be used in various drug-delivery applications.

Clays have traditionally been linked to health care, being used for centuries in the fight against infections and diseases. Similarly, biohybrids produced by combinations of clays and biological species through ‘bottom-up’ approaches have been evaluated over the past decade for biomedical and pharmaceutical uses. These biohybrids show interesting features such as biocompatibility and biodegradability which make them suitable for healthcare applications. The aim of the present communication was to review recent research contributions describing progress and the role of biohybrid materials based on clays in biomedicine and pharmacy disciplines. Emphasis will be on the authors’ own experience of this topic, particularly on aspects related to controlled drug-delivery systems, adjuvants of vaccines, and vectors for non-viral gene transfection. Bionanocomposites offer several advantages for use in the design of new and efficient pharmacological formulations for cutaneous and oral administration. In these systems, the drug is typically entrapped in the clay and protected by a biopolymer matrix, and both components contribute to a gradual release of the drug. Clay-based hybrids have also shown their efficacy in vaccines as they can act as nanocarriers of viral particles, due to the biomimetic interface created on the clay surface after adsorption of suitable biomolecules such as phospholipids, while the clay acts as an adjuvant to increase the efficacy of the vaccine. Finally, a new application of clays as non-viral vectors for controlled gene delivery is attracting increasing interest in the treatment of diverse diseases; clays such as sepiolite have demonstrated their ability to act as nanocarriers of nucleic acids and facilitate their transfection in mammalian cells.

Halloysite nanotubes (HNTs) are hollow clay nanotubes in the nanometer size range, made up of double-layered aluminum silicate mineral layers. HNTs represent an extremely versatile, safe, and biocompatible nanomaterial, used in a wide range of applications in biomedicine and nanomedicine. For example, they are used as transporters for the controlled release of drugs or genes, in tissue engineering, in the isolation of stem cells and cancer cells, and in bioimaging. Consequently, the assessment of the biocompatibility of HNTs has acquired considerable importance. In recent years, HNT composites have attracted attention due to their improved biocompatibility, compared to HNTs, suggesting potential for applications in tissue engineering or as vehicles for drugs or genes. In this review, recent advances in the application of HNTs and HNT composites in biomedicine are discussed to provide a valuable guide to scientists in the design and development of viable, functional bio-devices for biomedical applications.

Coarse-grained (CG) modelling with the Martini force field has come of age. By combining a variety of bead types and sizes with a new mapping approach, the newest version of the model is able to accurately simulate large biomolecular complexes at millisecond timescales. In this perspective, we discuss possible applications of the Martini 3 model in drug discovery and development pipelines and highlight areas for future development. Owing to its high simulation efficiency and extended chemical space, Martini 3 has great potential in the area of drug design and delivery. However, several aspects of the model should be improved before Martini 3 CG simulations can be routinely employed in academic and industrial settings. These include the development of automatic parameterisation protocols for a variety of molecule types, the improvement of backmapping procedures, the description of protein flexibility and the development of methodologies enabling efficient sampling. We illustrate our view with examples on key areas where Martini could give important contributions such as drugs targeting membrane proteins, cryptic pockets and protein–protein interactions and the development of soft drug delivery systems.

Electroporation has become a powerful technological platform for the electromanipulation of cells and tissues for various medical and biotechnological applications. Recently, nanoporation based on nanosecond pulsed electric fields (nsPEFs) has gained great attention due to its potential to permeabilize the membrane of small vesicles. Here, the authors propose and characterize, both experimentally and through multiphysics modeling, a grounded coplanar waveguide compliant with the wideband requirements for nanosecond pulses to be used for experiments of drug delivery with liposomes activated by nsPEFs.

Chitosan is one of the most versatile biopolymers available with established properties such as antimicrobial, antitumor, anti-inflammatory, mucoadhesive, and more. It has been in biomedical research for long, but still the bench-to-bedside translation is hampered because of viscosity and solubility issues. The only commercial application of chitosan has been in hemostatic dressings. Chitosan oligosaccharide (COS), on the other hand, is highly promising in a similar research area where chitosan's limitations come into the way. COS is highly soluble in water, and its viscosity is very less than that of the parent chitosan. Although COS retains properties very similar to those of chitosan, there has been minuscule volume of research on this water-soluble chitosan. COS has been successfully used as a drug delivery vehicle in various research. COS has also shown to have osteogenic ability. It has been used as a coating on experimental orthopedic implants because of its antibacterial properties. As of now, COS is not a much-explored biopolymer, although it could be an important biopolymer for its capacity in biomedical research. This article reviews various properties and reports of COS relevant for biomedical applications.

Hydrotalcites with heterogeneous distributions of anions between their layers were synthesized. Some synthesis parameters were studied to verify their influence on the anionic segregation properties of the hydrotalcites. The nature of the divalent cation and the crystallization method were most relevant. Zinc, in contrast to magnesium, assisted in discriminating carbonates and attracting nitrates to form hydrotalcites with heterogeneous distributions using microwave irradiation. Furthermore, the identification of this kind of hydrotalcite could be easily verified by determining the presence of a double reflection in the 003 X-ray diffraction (XRD) maximum, which definitively characterized a heterogeneous anion distribution. Finally, the reason as to why in some cases the hydrotalcite presented two reflections in the 003 XRD peak was elucidated.

A nanoparticle-based drug delivery system is first established by mesoporous silica encapsulating amino acid–intercalated layered double hydroxide (LDH) to construct nanocomposites AA-LDH@MS. The amino acids including phenylalanine (Phe) and histidine (His) with aromatic groups are intercalated into LDH as the cores Phe-LDH and His-LDH. These nanocomposites AA-LDH@MS display multispaces of the interlayer spaces of LDH and porous channels of mesoporous silica to load drugs. Moreover, amino acid molecules provide the interaction sites to improve effectively loading amounts of drugs. 5-Fluorouracil (5-FU) is used as the cargo molecules to observe the delivery in vitro. The results indicate that the maximum loading amounts of drugs are up to 392 mg/g at 60 °C for 12 h in the nanocomposite Phe-LDH@MS. All the nanocomposites exhibit the sustained release of 5-FU at pH 4 and pH 7.4. The Korsmeyer–Peppas model is used to fit the kinetic plot of the drug release in vitro, which concludes that 5-FU release from AA-LDH@MS belongs to Fickian diffusion.

Fabrication of simulated buccal mucosa could minimize sacrificing the animals (rabbits and pigs) to extract buccal mucosa for in vitro testing of buccal formulations. Novel artificial buccal mucosa was fabricated using eggshell membrane, extracted from poultry egg, and bovine submaxillary mucin. Chitosan oligosaccharide (COS)–based blended films were fabricated using solvent casting technique. Patches of equal dimensions were cut precisely from whole film. COS-based blended patches were analyzed for their physicochemical and mechanical properties. These patches, proposed to be used for buccal drug delivery, were tested for their mucoadhesion timing using the artificial mucosal membrane. The COS–PVA–blended patch displayed better mucoadhesion than chitosan oligosaccharide–alginate–blended film with the fabricated simulated buccal mucosa. Novel buccal mucosa mimetic–surface such as the one reported in this research article could prove to be a very useful tool in minimizing the use of excised animal buccal mucosa for mucoadhesion testing of buccal drug delivery formulations. Novel COS-blended films were fabricated as a proposed mucoadhesive buccal drug delivery vehicle.

The ability to control the movement of molecules is both fascinating scientifically as well as being critically important to the well-being of our planet and its people. In particular, the sustained release of molecules over prolonged periods at controlled rates has had and will continue to have enormous implications for the delivery of substances in medicine, agriculture, the environment, nutrition, aquaculture, household consumer products, and numerous other areas. This field is advancing at a rapidly accelerating pace. In this article, I largely discuss our own work, starting 45 years ago, in enabling the controlled release of macromolecules from biocompatible polymers. I also discuss the synthesis of novel materials to affect molecular movement and I then examine external approaches for controlling the movement of molecules through materials, using forces such as electric, acoustic, and magnetic fields. I further discuss approaches for controlling molecular movement through physiologic barriers, such as the skin, lung, and intestine. Finally, I outline several future areas of this field, including how it can affect the developing world, the ability to control the movement of molecules into mammalian cells, and the design of intelligent approaches to control molecular delivery.

In this project, we described the production of chrysin-loaded L-phenyl alanine (Phe)-coated iron oxide magnetic nanoparticles (chrysin@Phe@IOMNs). chrysin@Phe@IOMNs were characterized by X-ray diffraction, thermogravimetric analysis, fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. Next, hemocompatibility and biocompatibility of Phe-coated IOMNs were determined by hemolysis and MTT assays on HFF-2 and HEK-293 cell lines, respectively. Finally, the anticancer activity of chrysin@Phe@IOMNs was examined on MCF-7 cell line. The outcomes direct that as-prepared nanocarriers are nontoxic and biocompatible and also chrysin@Phe@IOMNs are appropriate for chrysin delivery and other hydrophobic therapeutic agents.

This study investigated the potential of halloysite nanotubes (HNTs) to improve the sustained release properties of chitosan (CS) microparticles cross-linked ionically with tripolyphosphate (TPP). Composite CS-HNTs microparticles were obtained by a simple and eco-friendly procedure based on a coaxial extrusion technique. Prior to encapsulation, a water-soluble model drug, verapamil hydrochloride (VH), was adsorbed successfully on HNTs. The microparticles were characterized by optical microscopy, Fourier transform infrared (FTIR) spectroscopy, differential thermal analysis/ thermogravimetric analysis (DTA/TG) and evaluated for encapsulation efficiency and drug-release properties. The composite particles had a slightly deformed spherical shape and micrometric size with average perimeters ranging from 485.4 ± 13.3 to 492.4 ± 11.9 μm. The results of FTIR spectroscopy confirmed non-covalent interactions between CS and HNTs within composite particle structures. The DTA and TG studies revealed increased thermal stability of the composite particles in comparison to the CS-TPP particles. Drug adsorption on HNTs prior to encapsulation led to an increase in encapsulation efficiency from 19.6 ± 2.9 to 84.3 ± 1.9%. In contrast to the rapid release of encapsulated model drug from CS-TPP microparticles, the composite CS-HNTs microparticles released drug in a sustained manner, showing the best fit to the Bhaskar model. The results presented here imply that HNTs could be used to improve morphology, encapsulation efficiency and sustained drug-release properties of CS microparticles cross-linked ionically with TPP.

New oral treatments are needed for all forms of leishmaniasis. Here, the improved oral efficacy of quercetin (Qc) and its penta-acetylated derivative (PQc) was evaluated in cutaneous leishmaniasis after encapsulation in lipid-core nanocapsules (LNCs) of poly(ε-caprolactone). Leishmania amazonensis-infected BALB/c mice were given 51 daily oral doses of free drugs (16 mg kg−1) or LNC-loaded drugs (0·4 mg kg−1). While treatment with free Qc reduced the lesion sizes and parasite loads by 38 and 71%, respectively, LNC-Qc produced 64 and 91% reduction, respectively. The antileishmanial efficacy of PQc was similar but not as potently improved by encapsulation as Qc. None of the treatments increased aspartate aminotransferase, alanine aminotransferase or creatinine serum levels. These findings indicate that when encapsulated in LNC, Qc and, to a lesser extent, PQc can safely produce an enhanced antileishmanial effect even at a 40-fold lower dose, with implications for the development of a new oral drug for cutaneous leishmaniasis.

A medication's pharmacokinetic properties can be as important as its efficacy in determining how successful a treatment is. Formulation plays a critical role in absorption, distribution, and elimination of a drug, which in turn can influence the clinical profile of a medication, including onset and duration of action, consistency of plasma levels, ability to cross the blood-brain barrier, and other factors. Advances in drug delivery technology mean that formulation is now an integral component in the development of a drug. Likewise, formulation is one of the factors that may influence selection of a medication to suit the needs of a particular patient. This article briefly reviews the technologies commonly applied in the development of psychotropic medications, with emphasis on the various oral modified-release formulations, and discusses how formulation can be used to optimize the efficacy and tolerability of psychotropic drugs.