Chitosan surface modification modulates the mucoadhesive, permeation and anti-angiogenic properties of gellan gum/bevacizumab nanoparticles.

Bevacizumab (BVZ) was the first monoclonal antibody approved by the FDA and has shown an essential advance in the antitumor therapy of colorectal cancer (CRC), however, the systemic action of BVZ administered intravenously can trigger several adverse effects. The working hypothesis of the study was to promote the modulation of the mucoadhesion properties and permeability of the BVZ through the formation of nanoparticles (NPs) with gellan gum (GG) with subsequent surface modification with chitosan (CS). NPs comprising BVZ and GG were synthesized through polyelectrolyte complexation, yielding spherical nanosized particles with an average diameter of 264.0 ± 2.75 nm and 314.0 ± 0.01 nm, polydispersity index of 0.182 ± 0.01 e 0.288 ± 0.01, and encapsulation efficiency of 29.36 ± 0.67 e 60.35 ± 0.27 mV, for NPs without (NP_BVZ) and with surface modification (NP_BVZ + CS). The results showed a good ability of nanoparticles with surface modification to modulate the NPs biological properties.

Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review.

The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.

Semiochemical delivery systems based on natural polymers to attract sand flies (Diptera: Psychodidae).

BACKGROUND: The successful use of semiochemicals to attract insects to traps is based on research on the most suitable compounds and their release profiles over time. Based on the group's promising results, matrices with a more adequate release profile and more eco-friendly properties for the release of 1-hexanol were developed. To use a more suitable prototype in the field, the most promising systems were added to a capsule and evaluated in a wind tunnel. Behavioral experiments were performed using the sand fly species, Lutzomyia longipalpis, to evaluate the efficacy of the proposed system. METHODS: Different delivery systems were developed by varying the polymer (gellan gum and pectin) ratio, crosslinker (aluminum chloride) concentration, and glutaraldehyde removal.The delivery systems were loaded with 1-hexanol, and their release profiles were evaluated using gravimetric analysis under ambient and high-humidity conditions. When the matrix system was placed inside a plastic container, modulations in the active release profile were observed and the system could be reused. Actid attraction behaviors of the sand fly species, Lu. longipalpis, were evaluated in a wind tunnel when exposed to 1-hexanol-loaded release systems at different times. RESULTS: Among the four formulations evaluated, System 2 (gellan gum and pectin in a 1:1 ratio with 5% aluminum chloride) exhibited the most promising release profile, with greater uniformity and longer compound release time. The maximum 1-hexanol release uniformity was achieved over a longer time, mainly every 24 h, under both ambient and high-humidity conditions. System 2 can be reused at least once with the same structure. The wind tunnel trials exhibited efficient activation and attraction of Lu. longipalpis to 1-hexanol after 24, 48, and 72 h in System 2 placed inside the capsules. CONCLUSIONS: The polymeric matrix supplemented with 1-hexanol and introduced in plastic capsules showed promising results in attracting sand flies. This system can be used as a solution for other attractive compounds as well as in other applications where their release needs to be controlled or prolonged.

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.

Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes.

Liposomes functionalized with cell-penetrating peptides are a promising strategy to deliver insulin through the nasal route. A hydrogel based on hydroxyethylcellulose (HEC) aqueous solution was prepared, followed by a subsequent addition of liposomes containing insulin solution functionalized with trans-activator of transcription protein of HIV-1 (TAT) or Penetratin (PNT). The formulations were characterized for rheological behavior, mucoadhesion, syringeability, in vitro release and in vivo efficacy. Rheological tests revealed non-Newtonian fluids with pseudoplastic behavior, and the incorporation of liposomes (HLI, HLITAT and HLIPNT) in hydrogels did not alter the behavior original pseudoplastic characteristic of the HEC hydrogel. Pseudoplastic flow behavior is a desirable property for formulations intended for the administration of drugs via the nasal route. The results of syringeability and mucoadhesive strength from HEC hydrogels suggest a viable vehicle for nasal delivery. Comparing the insulin release profile, it is observed that HI was the system that released the greatest amount while the liposomal gel promoted greater drug retention, since the liposomal system provides an extra barrier for the release through the hydrogel. Additionally, it is observed that both peptides tested had an impact on the insulin release profile, promoting a slower release, due to complexation with insulin. The in vitro release kinetics of insulin from all formulations followed Weibull's mathematical model, reaching approximately 90% of release in the formulation prepared with HEC-based hydrogels. Serum insulin levels and the antihyperglycemic effects suggested that formulations HI and HLI have potential as carriers for insulin delivery by the nasal pathway, a profile not observed when insulin was administered by subcutaneous injection or by the nasal route in saline. Furthermore, formulations functionalized with TAT and PNT can be considered promoters of late and early absorption, respectively.

Solid dispersions based on chitosan/hypromellose phthalate blends to modulate pharmaceutical properties of zidovudine.

Zidovudine (AZT) has been widely used alone or in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus. Its erratic oral bioavailability necessitates frequent administration of high doses, resulting in severe side effects. In this study, the design of mucoadhesive solid dispersions (SDs) based on chitosan (CS) and hypromellose phthalate (HP) was rationalized as a potential approach to modulate AZT physicochemical and pharmaceutical properties. SDs were prepared at different drug:polymer ratios, using an eco-friendly technique, which avoids the use of organic solvents. Particles with diameter from 56 to 73 µm and negative zeta potentials (-27 to -32 mV) were successfully prepared, achieving high drug content. Infrared spectroscopy revealed interactions between polymers but no interactions between the polymers and AZT. Calorimetry and X-ray diffraction analyses showed that AZT was amorphized into the SDs. The mucoadhesive properties of SDs were evidenced, and the control of AZT release rates from the matrix was achieved, mainly in acid media. The simple, low-cost, and scalable technology proposed for production of SDs as a carrier platform for AZT is an innovative approach, and it proved to be a feasible strategy for modulation the physico-chemical, mucoadhesive, and release properties of the drug.

Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review.

The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.

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.

Ionic Cross-Linking as a Strategy to Modulate the Properties of Oral Mucoadhesive Microparticles Based on Polysaccharide Blends.

Polymer blends of gellan gum (GG)/retrograded starch(RS) and GG/pectin (P) were cross-linked with calcium, aluminum, or both to prepare mucoadhesive microparticles as oral carriers of drugs or nano systems. Cross-linking with different cations promoted different effects on each blend, which can potentially be explored as novel strategies for modulating physical-chemical and mucoadhesive properties of microparticles. Particles exhibited spherical shapes, diameters from 888 to 1764 µm, and span index values lower than 0.5. Blends of GG:P cross-linked with aluminum resulted in smaller particles than those obtained by calcium cross-linking. GG:RS particles exhibited larger sizes, but cross-linking this blend with calcium promoted diameter reduction. The uptake rates of acid medium were lower than phosphate buffer (pH 6.8), especially GG:RS based particles cross-linked with calcium. On the other hand, particles based on GG:P cross-linked with calcium absorbed the highest volume of acid medium. The percentage of systems erosion was higher in acid medium, but apparently occurred in the outermost layer of the particle. In pH 6.8, erosion was lower, but caused expressive swelling of the matrixes. Calcium cross-linking of GG:RS promoted a significantly reduction on enzymatic degradation at both pH 1.2 and 6.8, which is a promising feature that can provide drug protection against premature degradation in the stomach. In contrast, GG:P microparticles cross-linked with calcium suffered high degradation at both pH values, an advantageous feature for quickly releasing drugs at different sites of the gastrointestinal tract. The high mucoadhesive ability of the microparticles was evidenced at both pH values, and the Freundlich parameters indicated stronger particle-mucin interactions at pH 6.8.

Oral delivery of micro/nanoparticulate systems based on natural polysaccharides for intestinal diseases therapy: Challenges, advances and future perspectives.

Colon-targeted oral delivery of drugs remains as an appealing and promising approach for the treatment of prevalent intestinal diseases (ID), such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Notwithstanding, there are numerous challenges to effective drug delivery to the colon, which requires the design of advanced strategies. Micro- and nanoparticles have received great attention as colon-targeted delivery platforms due to their reduced size and structural composition that favors the accumulation and/or residence time of drugs at the site of action and/or absorption, contributing to localized therapy. The choice by natural polysaccharides imparts key properties and advantages to the nano-in-microparticulate systems to effective colon-specific oral delivery. This review proposes to discuss the physiological barriers imposed by the gastrointestinal tract (GIT) against oral administration of drugs, as well as pathological factors and challenges of the ID for oral delivery of colon-targeted systems. We then provide an updated progress about polysaccharides-based colon-targeted drug delivery systems, including microparticulate, nanoparticulate and nano-in-microparticulate systems, highlighting their key properties, advantages and limitations to achieving targeted delivery and efficacious therapy within the colon. Lastly, we provide future perspectives, towards advances in the field and clinical translation of colon-targeted oral delivery systems for ID therapy.

N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan: Synthesis, physicochemical and biological properties.

Two samples of N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan (DPCat) with different average degrees of quaternization named as DPCat35 (DQ¯ = 35%) and DPCat80 (DQ¯ = 80%), were successfully synthesized by reacting glycidyltrimethylammonium chloride (GTMAC) with O-palmitoyl chitosan (DPCh) derivative (DS¯ = 12%). Such amphiphilic derivatives of chitosan were fully water-soluble at 1.0 < pH < 12.0 and showed significant electrostatic stability enhancement of a self-assembly micellar nanostructure (100-320 nm) due to its positively-charged out-layer. In vitro mucoadhesive and cytotoxicity essays toward healthy fibroblast cells (Balb/C 3T3 clone A31 cell), human prostate cancer (DU145) and liver cancer (HepG2/C3A) cell lines revealed that the biological properties of DPCat derivatives were strongly dependent on DQ¯. Additionally, DPCat35 had better interactions with the biological tissue and with mucin glycoproteins at pH 7.4 as well as exhibited potential to be used on the development of drug delivery systems for prostate and liver cancer treatment.

Determination of dexamethasone acetate in CETETH 20-based in liquid crystalline systems using HPLC.

Dexamethasone acetate (DEX), a potent anti-inflammatory, is used primarily in the treatment of inflammatory and autoimmune diseases. It was incorporated in CETETH 20 (polyoxyethylene 20 cetyl alcohol)-based liquid crystalline systems to enhance the purpose of the drug. Concomitant with the pharmaceutical technology performed, a HPLC method was developed and validated for the quantification of dexamethasone acetate in CETETH 20-based liquid crystalline systems for the evaluation of the drug in the new matrix. The method was performed using a C18 column with acetonitrile:methanol:water (35:35:30, v/v/v) as the mobile phase at a flow rate of 0.8 mL min-1 at 239 nm. The method was linear in the range of 1-25 µg mL-1 ; the limit of quantification and limit of detection were 0.05 and 0.16 µg mL-1 , respectively; the accuracy of the method was 99.92% (relative standard deviation < 1%), and it presented intra-day and inter-day precision with deviations less than 1%. In this context, the method was successfully used to determine the incorporation efficiency of DEX in CETETH 20-based liquid crystalline systems and can be easily used by pharmaceutical companies and laboratories around the world.

Computational and experimental approaches for chitosan-based nano PECs design: Insights on a deeper comprehension of nanostructure formation.

Nanostructured polyelectrolyte complexes (nano PECs) based on biopolymers are an important technological strategy to target drugs to the action and/or absorption site in a more effective way. In this work, computational studies were performed to predict the ionization, spatial arrangement and interaction energies of chitosan (CS), hyaluronic acid (HA), and hypromellose phthalate (HP), for the design of nano PEC carriers for methotrexate (MTX). The optimal pH range (5.0-5.5) for preparing nano PECs was selected by experimental and computational methodologies, favoring the polymers interactions. CS, HA, HP and MTX addition order was also rationalized, maximizing their interactions and MTX entrapment. Spherical nano-sized particles (256-575 nm, by dynamic light scattering measurement) with positive surface charge (+25.5 to +29.2 mV) were successfully prepared. The MTX association efficiency ranged from 20 to 32 %. XRD analyses evidenced the formation of a new material with an organized structure, in relation to raw polymers.

A Critical Review of Biological Properties, Delivery Systems and Analytical/Bioanalytical Methods for Determination of Bevacizumab.

Bevacizumab is a chimeric monoclonal human-murine antibody originated from murine monoclonal antibody (muMAb A4.6.1) with the human immunoglobulin IgG1. BVZ binds the extracellular portion of vascular endothelial growth factor receptors (VEGFR), which have tyrosine kinase activity. The mechanism of action of BVZ involves binding to VEGFR, Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), inducing homodimerization of two receptor subunits, and, consequently, autophosphorylation of their tyrosine kinase domains located inside the cytoplasm. With the advent of nanostructured systems it is increasingly necessary to look for safe analytical methods, ensuring the reliability of the results obtained by them, becoming essential to ensure the quality of medicines. In this work, the incorporation of bevacizumab in to different drug delivery systems was presented. Moreover, detailed investigation was performed about methods for qualitative and quantitative analyses of bevacizumab, including, biological fluids, and drug delivery systems, were investigated. Most recently high performance liquid chromatography coupled with various detectors, liquid chromatography, mass spectrometry and ELISA were used for this purpose. Thus, this review was performed to evaluate the benefits of bevacizumab carried by nanostructured systems and the analytical methods available for detection and quantification of these drugs.

Nanostructured polyelectrolyte complexes based on chitosan and sodium alginate containing rifampicin for the potential treatment of tuberculosis.

Nanostructured polyelectrolyte complexes (nano PECs) were obtained by polyelectrolyte complexation technique from chitosan (CS) and sodium alginate (SA). Different polymer proportions were tested, as well as the addition order and homogenization type, to assess the influence on the nano PECs characteristics. The spherical shape and nanometric scale of the systems were observed by scanning electron microscopy (SEM). Nano PECs size, PDI, and zeta potential (ZP) ranged from 252 to 616 nm, from 0.22 to 0.73 and -50 to 30 mV, respectively. The increase of polymer proportion and the ultra-turrax homogenization led to the enlargement of particles size and PDI. However, no influence was observed on the ZP. The NP1s-Rb and NP4s-Rb, obtained through the sonicator with rifampicin (RIF) added before the CS and SA complexation, were selected due to the most promising characteristics of diameter (301 and 402 nm), PDI (0.27 and 0.26), and RIF incorporation (78 and 69%). The release profiles of RIF incorporated in both nano PECs were similar, with a sustained release of the drug for 180 min in phosphate buffer pH 7.2. The Weibull and the Korsmeyer-Peppas models better describe the RIF release from NP1s-Rb and NP4s-Rb, respectively, demonstrating that the release process was driven by different mechanism according to the particle composition. The nano PECs were lyophilized to prolong it stability and for possible nebulization. The addition of dextrose to the system allowed for resuspension after lyophilization. Therefore, with the results obtained, the incorporation of RIF in nano PECs based on CS and SA presents a promising system for the treatment of tuberculosis.

Understanding the role of colon-specific microparticles based on retrograded starch/pectin in the delivery of chitosan nanoparticles along the gastrointestinal tract.

The encapsulation of nanoparticles within microparticles designed for specific delivery to the colon is a relevant strategy to avoid premature degradation or release of nanoparticles during their passage through the stomach and upper gastrointestinal tract (GIT), allowing the targeted delivery of chemotherapeutics to the colon after oral administration. Here, we designed an oral multiparticulate system to achieve targeted release in the colon. In this sense, chitosan nanoparticles (CS NPs) encapsulated with 5-fluorouracil (5-FU) and incorporated into retrograded starch and pectin (RS/P) microparticles were developed and their in vivo distribution along the mouse GIT after oral administration was monitored using multispectral optical imaging. In vitro release studies revealed that the encapsulation of CS NPs into RS/P microparticles promoted greater control of 5-FU release rates, with a significant reduction (53%) in acid media that might replicate that found in the stomach following oral administration. The evaluation of the in vivo biodistribution of the CS NPs in mice showed a faster clearance in the distribution pattern along the mouse GIT, i.e., a shorter transit time of CS NPs compared to CS NPs-loaded RS/P microparticles. Additionally, CS NPs alone showed non-specific absorption into the blood-stream with associated kidney accumulation, while for the CS NPs-loaded RS/P microparticles no significant accumulation was observed in blood or major clearance organs. This suggests the specific degradability of RS/P by the colon microbiota appears to have been decisive in the higher protection of the CS NPs along the GIT until release in the colon, preventing unwanted absorption into the bloodstream and major organs following oral administration. Our findings represent a proof of concept for the use of RS/P microparticles as potential carriers for delivering drug-loaded nanoparticles to the colon and this work will contribute to the development of oral-systems for colorectal cancer therapy.

Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections.

Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (21 × 21 × 31), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811-1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553-739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity.

Recent advances in hydrogels as strategy for drug delivery intended to vaginal infections.

Vaginal infections represent a clear women health problem due to the several issues as high recurrence rate, drug resistence and emergence of persistent strains. However, achieving improvements in therapeutic efficacy by using conventional formulations intended to vaginal drug delivery remains as a challenge due to anatomy and physiology of the vagina, since the secretion and renewal of vaginal fluids contribute to the removal of the dosage form. Hydrogels have been widely exploited aiming to achieve drug delivery directly into vaginal mucosa for local therapy due to their attractive features as increased residence time of the drug at the action site and control of drug release rates. Some polymers can aggregate specific properties to hydrogels as mucoadhesive, stimuli-responsive and antimicrobial, improving their interaction with the biological interface and therapeutic response. In this review, we highlight the advances, advantages and challenges of the hydrogels as drug and/or nanocarrier vehicles intended to the treatment of vaginal infections, emphasizing also the polymers and their properties more explored on the design these systems to improve the therapeutic effect on the vaginal tissue. In addition, this review can contribute for better exploitation these systems in search of new local treatments for bacterial vaginosis, candidiasis and trichomoniasis.

Chick embryo chorioallantoic membrane as a suitable in vivo model to evaluate drug delivery systems for cancer treatment: A review.

Cancer represents a significant public health problem. More than 18.1 million people are annually diagnosed with cancer and 9.6 million die mainly due to metastatic disease. Chemotherapy has been one of the main cancer treatment modalities; however, most of the chemotherapeutic agents are non-specific, exhibiting several toxic side effects, which compromises the patient's quality of life. Therefore, it is necessary to search for new therapeutic alternatives, using for example, drug delivery systems (DDS) to target cancer cells, increasing the selectivity of chemotherapeutic drugs. This approach is promising; however, it is crucial to evaluate the biological performance of the systems. Although mammalian models continue to be explored for clinical applications, they are time-consuming and very restrictive from the ethical and legal perspectives. Hence, the chick embryo chorioallantoic membrane (CAM) has been shown to be a suitable in vivo model since it allows a more appropriate model for the study of drugs and/or DDS performance than in vitro tests. Thereby, this article revises the recent advances of DDS for cancer therapy, evaluating the feasibility of the CAM model.

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.