Biopharmaceutical and nanotoxicological aspects of cyclodextrins for non-invasive topical treatments: A critical review.

Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability, in addition to protecting them against oxidation and UV radiation. Some of their characteristics are low toxicity, biodegradability, and biocompatibility. They are divided into α-, ß-, and γ-cyclodextrins, each with its own particularities. They can undergo surface modifications to improve their performances. Furthermore, their drug inclusion complexes can be made by various methods, including lyophilization, spray drying, magnetic stirring, kneading, and others. Cyclodextrins can solve several problems in drug stability when incorporated into dosage forms (including tablets, gels, films, nanoparticles, and suppositories) and allow better topical biological effects of drugs at administration sites such as skin, eyeballs, and oral, nasal, vaginal, and rectal cavities. However, as they are nanostructured systems and some of them can cause mild toxicity depending on the application site, they must be evaluated for their nanotoxicology and nanosafety aspects. Moreover, there is evidence that they can cause severe ototoxicity, killing cells from the ear canal even when applied by other administration routes. Therefore, they should be avoided in otologic administration and should have their permeation/penetration profiles and the in vivo hearing system integrity evaluated to certify that they will be safe and will not cause hearing loss.

The Emerging Landscapes to Drug Delivery Systems for the Treatment of Pancreatic Cancer.

Pancreatic Ductal Adenocarcinoma (PDA) is a highly metastatic tumor, and the liver is its first target, which restricts the use of medications. PDA is considered one of the most aggressive types of cancer in the world, with an extremely short survival time, depending on the stage of diagnosis. In non-surgical cases, chemotherapy alternatives are only effective in 40% to 60% of patients. The low efficiency of treatments occurs mainly due to the complex microenvironment in PDA, leading to chemoresistance to treatments and making it difficult to reach the affected tissue. A very important histological characteristic of PDA is the extremely dense stroma, which leads to low vascularization of tumor tissue. Consequently, the stroma environment causes less drug accumulation in tumor cells, even of selective and/or targeted drugs. Overcoming the stroma's microenvironment is a major challenge for therapies. Moreover, specific genes lead to direct chemoresistance in PDA due to their high progression. In this scenario, nanotechnology appears as an alternative to overcome these clinical challenges concerning two distinct ways: acting on the stroma or/and acting directly on the pancreatic tumor cells. Thus, this review aimed to highlight advances in the application of nanotechnology aiming to open up new landscapes against PDA. There are a huge number of nanoparticles carrying drugs in preclinical and clinical trials for the effective treatment of PDA. These works have been discussed, and based on the current scenario, the future prospects for an efficient treatment of PDA have been proposed.

Nanotechnology-based Drug Delivery Systems as Potential for Skin Application: A Review.

Administration of substances through the skin represents a promising alternative, in relation to other drug administration routes, due to its large body surface area, in order to offer ideal and multiple sites for drug administration. In addition, the administration of drugs through the skin avoids the first-pass metabolism, allowing an increase in the bioavailability of drugs, as well as reducing their side effects. However, the stratum corneum (SC) comprises the main barrier of protection against external agents, mainly due to its structure, composition and physicochemical properties, becoming the main limitation for the administration of substances through the skin. In view of the above, pharmaceutical technology has allowed the development of multiple drug delivery systems (DDS), which include liquid crystals (LC), cubosomes, liposomes, polymeric nanoparticles (PNP), nanoemulsions (NE), as well as cyclodextrins (CD) and dendrimers (DND). It appears that the DDS circumvents the problems of drug absorption through the SC layer of the skin, ensuring the release of the drug, as well as optimizing the therapeutic effect locally. This review aims to highlight the DDS that include LC, cubosomes, lipid systems, PNP, as well as CD and DND, to optimize topical skin therapies.

A Review of Properties, Delivery Systems and Analytical Methods for the Characterization of Monomeric Glycoprotein Transferrin.

Transferrin is a protein involved in iron uptake by cells and has been identified as a potential target for directing drug-loaded nanoparticles for cancer treatment and diagnosis. Most methods for conjugation of transferrin and nanoparticles involve the formation of a thioeter bond between thiolated transferrin and maleimide-containing nanoparticle. For nanoparticle development, it is important to perform a thorough physicochemical characterization, including quantification of the amount of transferrin functionalizing the delivery system. Thus, following the transferrin and nanoparticle chemical conjugation, an analytical method is need for transferrin quantification. Altogether, we revised both physicochemical and pharmacokinetics transferrin characteristics, the aspects of iron transport after interaction with transferrin, the development of transferrin targeted-nanoparticles, highlighting both their composition, synthesis methods and in vitro/in vivo evaluation. Furthermore, we addressed the analytical methods employed in protein quantification, including spectrophotometric/colorimetric, immunoassays, electrophoretic and chromatographic techniques used to identify and/or quantify of transferrin in biological matrices and drug delivery systems.