Current Drug Delivery - Current Issue

Because of low immunogenicity, ease of modification, and inherent biosafety, peptides have been well recognized as vehicles to deliver therapeutic agents to targeted regions with improved pharmacokinetic characteristics. Enzyme-responsive self-assembled peptides (ERSAPs) show superiority over their naive forms due to their enhanced targeting efficacy and long-retention property. In this review, we have summarized recent advances in the therapeutic application of ERSAPs, mainly focusing on their self-therapeutic properties and potential as vehicles to deliver different drugs.

Cell-penetrating peptides (CPPs) comprise short peptides of fewer than 30 amino acids, which are rich in arginine (Arg) or lysine (Lys). CPPs have attracted interest in the delivery of various cargos, such as drugs, nucleic acids, and other macromolecules over the last 30 years. Among all types of CPPs, arginine-rich CPPs exhibit higher transmembrane efficiency due to bidentate bonding between their guanidinium groups and negatively charged cellular components. Besides, endosome escape can be induced by arginine-rich CPPs to protect cargo from lysosome-dependent degradation. Here we summarize the function, design principles, and penetrating mechanisms of arginine-rich CPPs, and outline their biomedical applications in drug delivery and biosensing in tumors.

The blood-prostate barrier (BPB), a non-static physical barrier, stands as an obstacle between the prostate stroma and the lumen of the prostate gland tube. The barrier has the ability to dynamically regulate and strictly control the mass exchange between the blood and the prostate, thereby limiting drug penetration into the prostate. The basement membrane, fibrous stromal layer, capillary endothelial cell, prostatic ductal epithelial cell, lipid layer, etc., have been confirmed to be involved in the composition of the barrier structure and altered membrane permeability mainly by regulating the size of paracellular ion pores. Various studies have been conducted to improve the efficiency of drug therapy for prostate diseases by changing the administration approaches, improving barrier permeability and increasing drug penetration. To gain a full understanding of BPB, the composition of BPB, the methodology for evaluating the permeability of BPB and alterations in barrier function under pathological conditions are summarized in this review. To find a shortcut for drug delivery across BPB, the biodistribution of drugs in the prostate and different methods of improving drug penetration across BPB are outlined. This review offers an applied perspective on recent advances in drug delivery across BPB.

Glioblastoma multiforme is the most common and aggressive malignant tumor that affects the central nervous system, with high mortality and low survival. Glioblastoma multiforme treatment includes resection tumor surgery, followed by radiotherapy and chemotherapy adjuvants. However, the drugs used in chemotherapy present some limitations, such as the difficulty of crossing the blood-brain barrier and resisting the cellular mechanisms of drug efflux. The use of polymeric nanoparticles has proven to be an effective alternative to circumvent such limitations, as it allows the exploration of a range of polymeric structures that can be modified in order to control the biodistribution and cytotoxic effect of the drug delivery systems. Nanoparticles are nanometric in size and allow the incorporation of targeting ligands on their surface, favoring the transposition of the blood-brain barrier and the delivery of the drug to specific sites, increasing the selectivity and safety of chemotherapy. The present review has described the characteristics of chitosan, poly(vinyl alcohol), poly(lactic-co-glycolic acid), poly(ethylene glycol), poly(β-amino ester), and poly(ε-caprolactone), which are some of the most commonly used polymers in the manufacture of nanoparticles for the treatment of glioblastoma multiforme. In addition, some of the main targeting ligands used in these nanosystems are presented, such as transferrin, chlorotoxin, albumin, epidermal growth factor, and epidermal growth factor receptor blockers, explored for the active targeting of antiglioblastoma agents.

Melanoma is a malignant skin cancer type with a high lethality rate due to active metastasis. Among the risk factors for its development is exposure to ultraviolet radiation (UV) and phenotypical characteristics such as clear skin and eyes. Given the difficulties of the conventional therapy, the high cost of the treatment and the low bioavailability of drugs, it is important to develop new therapeutic methods to circumvent this situation. Nanosystems such as micelles, liposomes and nanoparticles present advantages when compared to conventional treatments. The objective of this paper is to carry out a literature review based on articles that dealt with the use of siRNA-loaded nanosystems for the treatment of melanoma, with trials carried out in vivo to assess tumor size. The search was conducted in the Web of Science and PubMed databases considering the last 5 years, that is, the period between January 2017 to December 2021. The “SiRNA and Drug Delivery Systems and Melanoma” keywords were used in both databases, and the articles were analyzed using the inclusion and exclusion criteria established for this paper. The results obtained indicated that using siRNA transported via nanosystems was capable of silencing the BRAF tumor genes and of reducing tumor size and weight, not presenting in vitro and/or in vivo toxicity. Such being the case, the development of these systems becomes a non-invasive and promising option for the treatment of melanoma.

Conjugated Linoleic Acid (CLA) is a polyunsaturated dietary fatty acid. Probiotics can biohydrogenate CLA with multiple health benefits, especially in cancer treatment. In vitro, in vivo, and clinical studies have confirmed CLA isomers to possess anti-cancer activity. CLA has demonstrated its potential as an alternative treatment for cancer and also used as an adjuvant to reduce the side effects of existing treatment methods. The mechanism of the anticancer activity of CLA is still not clear; however, it may involve intervention with the cell cycle and modulation of gene expression. A greater potential of CLA for cancer treatment has been supported by more and more clinical trials to evaluate its potential. Some advanced technologies are in progress to overcome the flaws of current methods and enhance the microbial production of CLA. In conclusion, nutritional enrichment as a functional food and direct consumption of CLA may contribute to cancer management.