The role of hyaluronic acid in the design and functionalization of nanoparticles for the treatment of colorectal cancer.

Despite advances in new approaches for colorectal cancer (CRC) therapy, intravenous chemotherapy remains one of the main treatment options; however, it has limitations associated with off-target toxicity, tumor cell resistance due to molecular complexity and CRC heterogeneity, which lead to tumor recurrence and metastasis. In oncology, nanoparticle-based strategies have been designed to avoid systemic toxicity and increase drug accumulation at tumor sites. Hyaluronic acid (HA) has obtained significant attention thanks to its ability to target nanoparticles (NPs) to CRC cells through binding to cluster-determinant-44 (CD44) and hyaluronan-mediated motility (RHAMM) receptors, along with its efficient biological properties of mucoadhesion. This review proposes to discuss the state of the art in HA-based nanoparticulate systems intended for localized treatment of CRC, highlighting the importance of the mucoadhesion and active targeting provided by this polymer. In addition, an overview of CRC will be provided, emphasizing the importance of CD44 and RHAMM receptors in this type of cancer and the current challenges related to this disease, and important concepts about the physicochemical and biological properties of HA will also be addressed. Finally, this review aims to contribute to the advancement of accuracy treatment of CRC by the design of new platforms based on by HA.

Evaluation of photodynamic therapy on nanoparticles and films loaded-nanoparticles based on chitosan/alginate for curcumin delivery in oral biofilms.

Nanoparticles and nanoparticle-loaded films based on chitosan/sodium alginate with curcumin (CUR) are promising strategies to improve the efficacy of antimicrobial photodynamic therapy (aPDT) for the treatment of oral biofilms. This work aimed to develop and evaluate the nanoparticles based on chitosan and sodium alginate encapsulated with CUR dispersed in polymeric films associated with aPDT in oral biofilms. The NPs were obtained by polyelectrolytic complexation, and the films were prepared by solvent evaporation. The photodynamic effect was evaluated by counting Colony Forming Units (CFU/mL). Both systems showed adequate characterization parameters for CUR release. Nanoparticles controlled the release of CUR for a longer period than the nanoparticle-loaded films in simulated saliva media. Control and CUR-loaded nanoparticles showed a significant reduction of 3 log10 CFU/mL against S. mutans biofilms, compared to treatment without light. However, biofilms of S. mutans showed no photoinactivation effect using films loaded with nanoparticles even in the presence of light. These results demonstrate the potential of chitosan/sodium alginate nanoparticles associated with aPDT as carriers for the oral delivery of CUR, offering new possibilities to improve the treatment of dental caries and infections. This work will contribute to advances in the search for innovative delivery systems in dentistry.

New Technological Approaches for Dental Caries Treatment: From Liquid Crystalline Systems to Nanocarriers.

Dental caries is the most common oral disease, with high prevalence rates in adolescents and low-income and lower-middle-income countries. This disease originates from acid production by bacteria, leading to demineralization of the dental enamel and the formation of cavities. The treatment of caries remains a global challenge and the development of effective drug delivery systems is a potential strategy. In this context, different drug delivery systems have been investigated to remove oral biofilms and remineralize dental enamel. For a successful application of these systems, it is necessary that they remain adhered to the surfaces of the teeth to allow enough time for the removal of biofilms and enamel remineralization, thus, the use of mucoadhesive systems is highly encouraged. Among the systems used for this purpose, liquid crystalline systems, polymer-based nanoparticles, lipid-based nanoparticles, and inorganic nanoparticles have demonstrated great potential for preventing and treating dental caries through their own antimicrobial and remineralization properties or through delivering drugs. Therefore, the present review addresses the main drug delivery systems investigated in the treatment and prevention of dental caries.

Polymeric Systems for Colon-specific Mesalazine Delivery in the Intestinal Bowel Diseases Management.

The anti-inflammatory 5-aminosalicylic acid (5-ASA) is the main therapeutic option used to prevent and treat inflammatory bowel diseases. The upper intestinal tract performs rapid and almost complete absorption of this drug when administered orally, making local therapeutic levels of the molecule in the inflamed colonic mucosa difficult to achieve. Micro and nanoparticle systems are promising for 5-ASA incorporation because the reduced dimensions of these structures can improve the drug's pharmacodynamics and contribute to more efficient and localized therapy. Together, the association of these systems with polymers will allow the release of 5-ASA through specific targeting mechanisms to the colon, as demonstrated in the mesalazine modified-release dosage form. This review will summarize and discuss the challenges for the oral administration of 5-ASA and the different colon-specific delivery strategies using polymers.

Exploiting Polymeric Films as a Multipurpose Drug Delivery System: a Review.

Polymeric films are drug delivery systems that maintain contact with the delivery tissue and sustain a controlled release of therapeutic molecules. These systems allow a longer time of drug contact with the target site in the case of topical treatments and allow the controlled administration of drugs. They can be manufactured by various methods such as solvent casting, hot melt extrusion, electrospinning, and 3D bioprinting. Furthermore, they can employ various polymers, for example PVP, PVA, cellulose derivatives, chitosan, gelling gum, pectin, and alginate. Its versatility is also applicable to different routes of administration, as it can be administered to the skin, oral mucosa, vaginal canal, and eyeballs. All these factors allow numerous combinations to obtain a better treatment. This review focuses on exploring some possible ways to develop them and some particularities and advantages/disadvantages in each case. It also aims to show the versatility of these systems and the advantages and disadvantages in each case, as they bring the opportunity to develop different medicines to facilitate therapies for the most diverse purposes .

New insights into physicochemical aspects involved in the formation of polyelectrolyte complexes based on chitosan and dextran sulfate.

Polyelectrolyte complexation is a technique based on interactions between polyelectrolytes of opposite charges driven by supramolecular interactions. Although many studies address the formation of polyelectrolyte complexes (PECs), few explore strategies and tools to select the best working conditions and are often based on empirical choices. This study evaluates the influence of pH, molecular weight, and polymeric proportion on the formation of PECs based on chitosan:dextran sulfate. In addition, it assesses the approaches that study the influence of pH on the zeta potential of polymeric dispersions as a tool in the design of PECs. Results showed that nanoparticles with an excess of polycation formed aggregates, while an excess of dextran sulfate reduced the size of the particles. The graph of zeta potential as a function of pH proved to be a promising tool in the choice of polymers and a better pH condition in the development of PECs.

Polymeric-based drug delivery systems for veterinary use: State of the art.

One of the challenges to the success of veterinary pharmacotherapy is the limited number of drugs and dosage forms available exclusively to this market, due to the interspecies variability of animals, such as anatomy, physiology, pharmacokinetics, and pharmacodynamics. For this reason, studies in this area have become a highlight, since they are still scarce in comparison with those on human drug use. To overcome many limitations related to the bioavailability, efficacy, and safety of pharmacotherapy in animals, especially livestock and domestic animals, polymers-based drug delivery systems are promising tools if they guarantee greater selectivity and less toxicity in dosage forms. In addition, these tools may be developed according to the great interspecies variability. To contribute to these discussions, this paper provides an updated review of the major polymer-based drug delivery systems projected for veterinary use. Traditional and innovative drug delivery systems based on polymers are presented, with an emphasis on films, microparticles, micelles, nanogels, nanoparticles, tablets, implants and hydrogel-based drug delivery systems. We discuss important concepts for the veterinarian about the mechanisms of drug release and, for the pharmacist, the advantages in the development of pharmaceutical forms for the animal population. Finally, challenges and opportunities are presented in the field of pharmaceutical dosage forms for veterinary use in response to the interests of the pharmaceutical industry.

The role of polysaccharides from natural resources to design oral insulin micro- and nanoparticles intended for the treatment of Diabetes mellitus: A review.

Oral administration of insulin (INS) would represent a revolution in the treatment of diabetes, considering that this route mimics the physiological dynamics of endogenous INS. Nano- and microencapsulation exploiting the advantageous polysaccharides properties has been considered an important technological strategy to protect INS against harsh conditions of gastrointestinal tract, in the same time that improve the permeability via transcellular and/or paracellular pathways, safety and in some cases even selectivity for targeting delivery of INS. In fact, some polysaccharides also give to the systems functional properties such as pH-responsiveness, mucoadhesiveness under specific physiological conditions and increased intestinal permeability. In general, all polysaccharides can be functionalized with specific molecules becoming more selective to the cells to which INS is delivered. The present review highlights the advances in the past 10 years on micro- and nanoencapsulation of INS exploiting the unique natural properties of polysaccharides, including chitosan, starch, alginate, pectin, and dextran, among others.

Monoclonal Antibodies Carried in Drug Delivery Nanosystems as a Strategy for Cancer Treatment.

Monoclonal antibodies carried in nanosystems have been extensively studied and reported as a promising tool for the treatment of various types of cancers. Monoclonal antibodies have great advantages for the treatment of cancer because their protein structure can bind to the target tissue; however, it has some challenges such as denaturation following heat exposure and extreme values of pH, temperature and solvents, the ability to undergo hydrolysis, oxidation and deamination and the formation of non-native aggregates, which compromise drug stability to a large extent. In addition to these characteristics, they suffer rapid elimination when in the blood, which results in a short half-life and the production of neutralizing antibodies, rendering the doses ineffective. These challenges are overcome with encapsulation in nanosystems (liposomes, polymer nanoparticles, cyclodextrins, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers and micelles) due to the characteristics of improving solubility, permeability, and selectivity only with tumor tissue; with that, there is a decrease in side effects beyond controlled release, which is critical to improving the therapeutic efficacy of cancer treatment. The article was divided into different types of nanosystems, with a description of their definitions and applications in various types of cancers. Therefore, this review summarizes the use of monoclonal antibodies encapsulated in nanosystems and the description of clinical studies with biosimilars. Biosimilars are defined as products that are similar to monoclonal antibodies which are produced when the patent for the monoclonal antibodies expires.

Current applications of drug delivery nanosystems associated with antimicrobial photodynamic therapy for oral infections.

The oral cavity is colonized by several species of microorganisms that can cause dental caries, periodontal diseases, candidiasis, endodontic infections, and, among other diseases related to the dental field. Conventional treatment consists of mechanical removal associated with systemic administration of antimicrobials, which can cause various side effects and microbial resistance. In this context, alternative therapies have been developed, including Antimicrobial Photodynamic Therapy (aPDT). For the improvement of therapy, the implementation of nanotechnology is very important to optimize the delivery system of the dyes or photosensitizers on biological targets. Besides, this combination provides a non-invasive treatment, better solubility and bioavailability, delivery to the target site, controlled release and protection against external and physical-chemical factors, low side effects, and, unlikely resistant species. Although, there are numerous researches on aPDT and nanotechnology, few review articles based on the combination of these three aspects: nanosystems, aPDT and oral infections are available. For this reason, this article aims to discuss the advances and advantages of this combination. Therefore, this article was divided into different types of nanosystems (organic and inorganic nanoparticles) associated with aPDT bringing a description of it is definitions, properties, and, applications in oral infections.

Nanosystems against candidiasis: a review of studies performed over the last two decades.

The crescent number of cases of candidiasis and the increase in the number of infections developed by non-albicans species and by multi-resistant strains has taken the attention of the scientific community, which has been searching for new therapeutic alternatives. Among the alternatives found the use of nanosystems for delivery of drugs already commercialized and new biomolecules have grown, in order to increase stability, solubility, optimize efficiency and reduce adverse effects. In view of the growing number of studies involving technological alternatives for the treatment of candidiasis, the present review came with the intention of gathering studies from the last two decades that used nanotechnology for the treatment of candidiasis, as well as analysing them critically and pointing out the future perspectives for their application with this purpose. Different studies were considered for the development of this review, addressing nanosystems such as metallic nanoparticles, mesoporous silica nanoparticles, polymeric nanoparticles, liposomes, nanoemulsion, microemulsion, solid lipid nanoparticle, nanostructured lipid carrier, lipidic nanocapsules and liquid crystals; and different clinical presentations of candidiasis. As a general overview, nanotechnology has proven to be an important ally for the treatment against the diversity of candidiasis found in the clinic, whether in increasing the effectiveness of commercialized drugs and reducing their adverse effects, as well as allowing exploring more effectively properties therapeutics of new biomolecules.

Advances and challenges in nanocarriers and nanomedicines for veterinary application.

To ensure success in the development and manufacturing of nanomedicines requires forces of an interdisciplinary team that combines medicine, engineering, chemistry, biology, material and pharmaceutical areas. Numerous researches in nanotechnology applied to human health are available in the literature. Althought, the lack of nanotechnology-based pharmaceuticals products for use exclusively in veterinary pharmacotherapy creates a potential area for the development of innovative products, as these animal health studies are still scarce when compared to studies in human pharmacotherapy. Nano-dosage forms can ensure safer and more effective pharmacotherapy for animals and can more be safer for the consumers of livestock products, once they can offer higher selectivity and smaller toxicity associated with lower doses of the drugs. In addition, the development and production of nanomedicines may consolidate the presence of pharmaceutical laboratories in the global market and can generate greater profit in a competitive business environment. To contribute to this scenario, this article provides a review of the main nanocarriers used in nanomedicines for veterinary use, with emphasis on liposomes, nanoemulsions, micelles, lipid nanoparticles, polymeric nanoparticles, mesoporous silica nanoparticles, metallic nanoparticles and dendrimers, and the state of the art of application of these nanocarriers in drug delivery systems to animal use. Finnaly, the major challenges involved in research, scale-up studies, large-scale manufacture, analytical methods for quality assessment, and regulatory aspects of nanomedicines were discussed.

Qualitative and quantitative analysis of formaldehyde in samples of hair straighteners and suitability of the labels

Formaldehyde is an active compound, irregularly used in hair products, that has the property of straighten and waterproofing the wires. However, it is highly toxic and can stimulate dermatological hypersensitivity and cancer. In this context it is of fundamental importance the inspection of these products that can be used in safe conditions for the consumer, without formaldehyde in concentrations higher than the allowed. Thus, the aim of this research was the qualitative and quantitative identification formaldehyde in samples of hair straighteners that was obtained by donation in the beauty salons of Araraquara-SP. In addition, the analysis of the packaging labels of the products tested were conducted, following the requirements of the national legislation - RDC 07/2015 which defines the mandatory labeling standards for cosmetic products. A qualitative analysis for formaldehyde identification is based on the formation of a purple colored complex. The quantitative analysis was performed by spectrophotometry. The qualitative and quantitative formaldehyde analysis methods were applied to 13 bottles of hair straighteners. When submitted to qualitative analysis, all samples showed formaldehyde presence. The quantitative analysis demonstrated that the samples identified as B, C, D, E, G, H, I, J and M presented formaldehyde concentration of 3.5 to 14.5%, which is above of the limit recommended by the National Health Surveillance Agency (ANVISA), of 0.2%. In the label analysis, in all samples were found irregularities.(AU)

A paper platform for colorimetric determination of aluminum hydrochloride in antiperspirant samples.

A simple, fast, low-cost, portable, and eco-friendly method using a spot test on a paper platform, together with diffuse reflectance spectroscopy, was developed and validated for the quantification of aluminum hydrochloride, a potential neurotoxic agent, in antiperspirant samples. The determination of aluminum hydrochloride was performed at a wavelength of 615 nm, by measuring consumption of the purple colorimetric reagent Alizarin S, due to reaction with aluminum. The linear range was from 10.0 to 125.0 mg L-1 and could be described by the equation: AR = 0.4479 - 0.002543 CAl (R = 0.999). The limits of detection (LOD) and quantification (LOQ) were 3.06 and 10.2 mg L-1, respectively. The method was specific, accurate, and repeatable, with relative standard deviation (RSD) <5.0%. The recovery was between 92.2 and 103.4%. The method was successfully used for the determination of aluminum hydrochloride in commercial antiperspirant samples, revealing concentrations below the maximum permitted by current legislation.