Oral Delivery of Protein Drugs via Lysine Polymer-Based Nanoparticle Platforms.

Oral delivery of proteins has opened a new perspective for the treatment of different diseases. However, advances of oral protein formulation are usually hindered by protein susceptibility and suboptimal absorption in the gastrointestinal tract (GIT). Polymeric nano drug delivery systems are considered revolutionary candidates to solve these issues, which can be preferably tunable against specific delivery challenges. Herein, a tailored family of lysine-based poly(ester amide)s (Lys-aaPEAs) is designed as a general oral protein delivery platform for efficient protein loading and protection from degradation. Insulin, as a model protein, can achieve effective internalization by epithelial cells and efficient transport across the intestinal epithelium layer into the systemic circulation, followed by controlled release in physiological environments. After the oral administration of insulin carried by Lys-aaPEAs with ornamental hyaluronic acid (HA), mice with type 1 diabetes mellitus showed an acceptable hypoglycemic effect with alleviated complications. A successful oral insulin delivery is associated with patient comfort and convenience and simultaneously avoids the risk of hypoglycemia compared with injections, which is of great feasibility for daily diabetes therapy. More importantly, this versatile Lys-aaPEAs polymeric library can be recognized as a universal vehicle for oral biomacromolecule delivery, providing more possibilities for treating various diseases.

Natural Soybean Milk-Derived Bioactive Coatings for Enhanced Wound Healing.

Foodborne biomaterials, derived from diets, comprise selfassembled collections of many micro- or nanoscale units with abundant nutrients and active substances. In this study, soybean milk (SBM) was selected as a tissue engineering product for simple and feasible wound repair. SBM is a common drink prepared from soybeans and is rich in soy protein, soy isoflavones, and other bioactive components. Thus, SBM has substantial potential for antioxidation and tissue remodeling. Here, the multifunctional effect of SBM as a bioactive coating for promoting wound healing was studied. The results showed that SBM has good biocompatibility and biological activity. It efficiently scavenges intracellular reactive oxygen species, significantly enhances epithelial cell migration, and improves angiogenesis, thereby accelerating tissue remodeling. The results of animal experiments further confirmed that the SBM-bioinspired coating has promising applications for cutaneous wound regeneration.

Delivery of enzalutamide via nanoparticles for effectively inhibiting prostate cancer progression.

Androgen deprivation therapy has been used as a standard clinical treatment for prostate cancer, but the disease generally progresses to castration-resistant prostate cancer in a very short time. Enzalutamide (ENZ) is an emerging second-generation androgen receptor (AR) antagonist used for the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC). However, due to the rapid onset of drug resistance, it provides only a modest increase in survival. Here, we propose a convenient and effective androgen receptor antagonist drug delivery strategy, that is, the use of a biocompatible nanoparticle (NP) drug delivery system for drug delivery to improve its bioavailability and therapeutic performance. Although the particle size of the phenylpropyl polymer (8P4) nanoparticles is small, it has a high drug-carrying capacity. ENZ-8P4 NPs can increase drug delivery efficiency, enhance drug cytotoxicity, and reduce the half-inhibitory concentration (IC50) of the drug. In addition, in vivo experiments confirmed that ENZ-8P4 preferentially accumulates in the tumor and significantly inhibits tumor growth. Hence, the 8P4 drug delivery system loaded with enzalutamide has excellent potential for the treatment of prostate cancer.

More natural more better: triple natural anti-oxidant puerarin/ferulic acid/polydopamine incorporated hydrogel for wound healing.

BACKGROUND: During wound healing, the overproduction of reactive oxygen species (ROS) can break the cellular oxidant/antioxidant balance, which prolongs healing. The wound dressings targeting the mitigation of ROS will be of great advantages for the wound healing. puerarin (PUE) and ferulic acid (FA) are natural compounds derived from herbs that exhibit multiple pharmacological activities, such as antioxidant and anti-inflammatory effects. Polydopamine (PDA) is made from natural dopamine and shows excellent antioxidant function. Therefore, the combination of natural antioxidants into hydrogel dressing is a promising therapy for wound healing. RESULTS: Hydrogel wound dressings have been developed by incorporating PUE or FA via PDA nanoparticles (NPs) into polyethylene glycol diacrylate (PEG-DA) hydrogel. This hydrogel can load natural antioxidant drugs and retain the drug in the gel network for a long period due to the presence of PDA NPs. Under oxidative stress, this hydrogel can improve the activity of superoxide dismutase and glutathione peroxidase and reduce the levels of ROS and malondialdehyde, thus preventing oxidative damage to cells, and then promoting wound healing, tissue regeneration, and collagen accumulation. CONCLUSION: Overall, this triple antioxidant hydrogel accelerates wound healing by alleviating oxidative injury. Our study thus provides a new way about co-delivery of multiple antioxidant natural molecules from herbs via antioxidant nanoparticles for wound healing and skin regeneration.

Biomedical applications of methionine-based systems.

Methionine (Met), an essential amino acid in the human body, possesses versatile features based on its chemical modification, cell metabolism and metabolic derivatives. Benefitting from its multifunctional properties, Met holds immense potential for biomedical applications. In this review, we systematically summarize the recent progress in Met-based strategies for biomedical applications. First, given the unique structural characteristics of Met, two chemical modification methods are briefly introduced. Subsequently, due to the disordered metabolic state of tumor cells, applications of Met in cancer treatment and diagnosis are summarized in detail. Furthermore, the efficacy of S-adenosylmethionine (SAM), as the most important metabolic derivative of Met, for treating liver diseases is mentioned. Finally, we analyze the current challenges and development trends of Met in the biomedical field, and suggest that Met-restriction therapy might be a promising approach to treat COVID-19.

Multistage Nanoparticle Delivery System-A New Approach to Cancer Therapeutics.

Traditional methods of tumor therapy have many limitations. Thus, cancer nanomedicine is developing rapidly as a new treatment for tumors. In the past decade, the literature in this field has almost doubled every two years. However, the therapeutic nanoparticle (NP) platforms that have been approved for cancer treatment have not achieved the expected results in clinical application. Cancer nanomedicine still faces many obstacles and challenges. An abnormal cancer vascular system and a thick interstitial matrix can impose physiological barriers. As a result, drug delivery in tumor tissue depends mainly on diffusion. The diffusion efficiency of large NPs is poor; they are trapped around the blood vessels. Smallmolecule drug conjugates (SMDCs), miniaturized biologic drug conjugates (mBDCs), and small NPs can pass through this barrier. However, poor aggregation in tumors, easy elimination, and poor pharmacokinetics (PK) limit their therapeutic effects. In recent years, a selective new multistage delivery system was proposed to solve the challenge of infiltration. By incorporating smaller NPs or molecular drugs into large controlled-release particles for multistep delivery to tumors, we can make full use of the advantageous pharmacokinetics, the accumulation of large particles in the tumor, and the deep infiltration of small particles. In addition to changing the particle size, the multistage NP delivery system can also change the shape, charge, flexibility, and surface coating of the NPs to enhance penetration. Based on recent multistage delivery system research, this review expounds on the main direction of multistage delivery considering the ways in which large particles are triggered to release small particles.

Polydopamine/puerarin nanoparticle-incorporated hybrid hydrogels for enhanced wound healing.

Oxidative damage generated by various biochemical pathways can disrupt the oxidant/antioxidant balance in cells, causing slow wound healing and tissue regeneration; in this regard, a hydrogel dressing with antioxidant properties can promote wound healing; however, its design is still a challenge. Herein, a polydopamine/puerarin (PDA/PUE) nanoparticle-incorporated polyethylene glycol diacrylate hybrid hydrogel (PEG-DA/PDA/PUE) with antioxidant properties was prepared and used as a wound-healing material. Experimental observations indicated that the PEG-DA/PDA/PUE hydrogel possessed excellent swelling capacity and mechanical property. Moreover, the antioxidant capability was enhanced with an increase in the concentration of polydopamine/puerarin nanoparticles in the hydrogel. The hydrogel presented good cell proliferation and antioxidant activity, including a decrease in ROS and increase in the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity under oxidative stress conditions. Furthermore, the full-thickness skin-defect-regeneration process could be accelerated via the antioxidant hydrogel treatment. This study validated the potential applications of an antioxidant hydrogel for wound healing.

Poly(ester amide)-based hybrid hydrogels for efficient transdermal insulin delivery.

Transdermal drug delivery is an attractive, non-invasive treatment. It can avoid first-pass hepatic metabolism and provides the possibility of self-administration. Hydrogels are promising biomaterials due to their important qualities such as biocompatibility and biodegradability. Recently, there has been tremendous growth in the area of hydrogels for transdermal drug delivery. In this work, a new kind of arginine-based poly(ester amide) (Arg-PEA) and polyethylene glycol diacrylamide (PEG-DA) hybrid hydrogel was developed for transdermal drug delivery. The hydrogels not only possess excellent swelling capacity, but also have good mechanical properties, which were then evaluated as drug delivery agents using insulin as a model system. Cytotoxicity testing and in vivo skin irritation tests demonstrated that the hydrogels were biocompatible. Finally, the results indicated that the prepared hydrogels could not only perform transdermal drug delivery, but also might regulate blood glucose levels in a mouse model with streptozotocin-induced diabetes.