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Recent estimates indicate that tuberculosis (TB) is the leading cause of death worldwide, alongside the human immunodeficiency virus (HIV) infection. The current treatment is effective, but is associated with severe adverse-effects and noncompliance to prescribed regimens. An alternative route of drug delivery may improve the performance of existing drugs, which may have a key importance in TB control and eradication. Recent advances and emerging technologies in nanoscale systems, particularly nanoparticles (NPs), have the potential to transform such approach to human health and disease. Until now, several nanodelivery systems for the pulmonary administration of anti-TB drugs have been intensively studied and their utility as an alternative to the classical TB treatment has been suggested. In this context, this review provides a comprehensive analysis of recent progress in nanodelivery systems for pulmonary administration of anti-TB drugs. Additionally, more convenient and cost-effective alternatives for the lung delivery, different types of NPs for oral and topical are also being considered, and summarized in this review. Lastly, the future of this growing field and its potential impact will be discussed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (-)-Epigallocatechin-3-gallate (EGCG) is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG's properties and potentiate its anti-tumoral activity.

Understanding how nanoparticles' properties influence their cellular interactions is a bottleneck for improving the design of carriers. Macrophage polarization governs their active role in solving infections or tissue repair. To unravel the effect of carbohydrate-targeting mannose receptors on the macrophage surface, drug-free fucoidan/chitosan nanoparticles were functionalized using mannose (M) and mannan (Mn). Polyelectrolyte complex nanoparticles were obtained upon chitosan self-assembly using fucoidan. The functionalized nanoparticles were characterized in terms of their physicochemical characteristics, chemical profile, and carbohydrate orientation. The nanoparticles varied in size from 200 to 400 nm, were monodisperse, and had a stable negative zeta potential with a low aggregation tendency. The nonfunctionalized and functionalized nanoparticles retained their properties for up to 12 weeks. Cell viability and internalization studies were performed for all the designed nanoparticles in the THP-1 monocytes and THP-1-differentiated macrophages. The expression of the mannose receptor was verified in both immune cells. The carbohydrate-functionalized nanoparticles led to their activation and the production of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α. Both M- and Mn-coated nanoparticles modulate macrophages toward an M1-polarized state. These findings demonstrate the tailoring of these nanoplatforms to interact and alter the macrophage phenotype in vitro and represent their therapeutic potential either alone or in combination with a loaded drug for future studies. [ABSTRACT FROM AUTHOR]

Breast cancer was responsible for the deaths of 626,679 women in 2018. After decades of research, the mortality rates remain high. While the barrier of selectively killing tumor cells is not yet overcome, the search for targeted therapeutics continues. The use of nanomedicine in cancer treatment has opened up new possibilities for more precise drug-delivery systems. This review aimed to gather information and analyze recent clinical trials evaluating the therapeutic effects of nanoparticles in the treatment of metastatic breast cancer. To accomplish this, the clinicaltrials.gov database was consulted, and after employing specific exclusion criteria, 11 clinical trials were selected. Nanoparticle albumin-stabilized paclitaxel was evaluated in ten clinical trials and paclitaxel-incorporating polymeric micelles were assessed in one clinical trial. Overall, this review confirmed a clinical benefit in the use of nanoparticle albumin-stabilized paclitaxel for the treatment of breast cancer, with reduced toxicity when compared to first-line treatments. Three studies did not meet the primary endpoint, however, and so the authors advised further evaluations. Although the use of nanomedicine is revolutionizing the cancer field, to integrate this regimen into generalized clinical treatment, additional clinical trials must be performed to achieve a favorable safety and efficacy profile. [ABSTRACT FROM AUTHOR]

Aim: Design nanostructured lipid carriers (NLC) to facilitate drug delivery to tuberculosis-infected areas, exploiting macrophage mannose receptors and assess their uptake in a 3D human lung model. Materials & methods: NLCs and mannosylated-NLCs were synthetized and characterized. Their uptake and biocompatibility were tested in a 3D human lung model. Results: The formulations have appropriate size (170–202 nm) and morphology for lung deposition. Cell membrane integrity was maintained and no significant pro-inflammatory cytokine (IL-1β, IL-8 and TNF-α) secretion or morphological changes were observed 24 h post nanoparticles exposure. NLCs and mannosylated NLCs were distributed in the apical side of the lung tissue, both in macrophages and in epithelial cells. Conclusion: NLCs are biocompatible carriers and can be used for pulmonary drug delivery. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is considered by the World Health Organization as a high priority pathogen for which new therapies are needed. This is particularly important for biofilm implant-associated infections once the only available treatment option implies a surgical procedure combined with antibiotic therapy. Consequently, these infections represent an economic burden for Healthcare Systems. A new strategy has emerged to tackle this problem: for small bugs, small particles. Here, we describe how nanotechnology-based systems have been studied to treat S. aureus biofilms. Their features, drawbacks and potentialities to impact the treatment of these infections are highlighted. Furthermore, we also outline biofilm models and assays required for preclinical validation of those nanosystems to smooth the process of clinical translation. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is still a devastating disease and more people have died of TB than any other infectious diseases throughout the history. The current therapy consists of a multidrug combination in a long-term treatment, being associated with the appearance of several adverse effects. Thus, solid lipid nanoparticles (SLNs) were developed using mannose as a lectin receptor ligand conjugate for macrophage targeting and to increase the therapeutic index of rifampicin (RIF). The developed SLNs were studied in terms of diameter, polydispersity index, zeta potential, encapsulation efficiency (EE) and loading capacity (LC). Morphology, in vitro drug release and differential scanning calorimetry studies, macrophage uptake studies, cell viability and storage stability studies were also performed. The diameter of the SLNs obtained was within the range of 160-250 nm and drug EE was above 75%. The biocompatibility of M-SLNs was verified and the internalization in macrophages was improved with the mannosylation. The overall results suggested that the developed mannosylated formulations are safe and a promising tool for TB therapy targeted for macrophages. [ABSTRACT FROM AUTHOR]

Aim: This work aims to develop a mannosylated nanostructured lipid carrier (NLC) loaded with rifampicin to improve tuberculosis treatment. Materials & methods: An active targeting strategy was used and the nanoparticles were characterized. Effects on cell viability and the antimycobacterial activity of the nanoformulations were evaluated. Results: The nanoparticles developed exhibited a size of about 315 nm and polydispersity <0.2. The drug encapsulation efficiency was higher than 90% and its release was sensitive to pH. The mannosylated NLCs showed efficient uptake by bone marrow derived macrophages. Further, rifampicin-loaded mannosylated NLCs were more efficient in inducing a decrease of intracellular growth of mycobacteria. Conclusion: The NLCs developed can be used as a promising carrier for safer and efficient management of tuberculosis. [ABSTRACT FROM AUTHOR]

Nowadays, the society is facing a large health problem with the rising of new diseases, including cancer, heart diseases, diabetes, neurodegenerative diseases, and obesity. Thus, it is important to invest in substances that enhance the health of the population. In this context, epigallocatechin gallate (EGCG) is a flavonoid found in many plants, especially in tea. Several studies support the notion that EGCG has several benefits in fighting cancer, heart diseases, diabetes, and obesity, among others. Nevertheless, the poor intestinal absorbance and instability of EGCG constitute the main drawback to use this molecule in prevention and therapy. The encapsulation of EGCG in nanocarriers leads to its enhanced stability and higher therapeutic effects. A comprehensive review of studies currently available on the encapsulation of EGCG by means of nanocarriers will be addressed. [ABSTRACT FROM AUTHOR]

Purpose: The freezing step in lyophilization is the most determinant for the quality of biopharmaceutics. Using insulin as model of therapeutic protein, our aim was to evaluate the freezing effect in the stability and bioactivity of insulin-loaded PLGA nanoparticles. The performance of trehalose, sucrose and sorbitol as cryoprotectants was evaluated. Methods: Cryoprotectants were co-encapsulated with insulin into PLGA nanoparticles and lyophilized using an optimized cycle with freezing at −80°C, in liquid nitrogen, or ramped cooling at −40°C. Upon lyophilization, the stability of protein structure and in vivo bioactivity were assessed. Results: Insulin was co-encapsulated with cryoprotectants resulting in particles of 243-394 nm, zeta potential of −32 to −35 mV, and an association efficiency above 90%. The cryoprotectants were crucial to mitigate the freezing stresses and better stabilize the protein. The insulin structure maintenance was evident and close to 90%. Trehalose co-encapsulated insulin-loaded PLGA nanoparticles demonstrated enhanced hypoglycemic effect, comparatively to nanoparticles without cryoprotectant and added with trehalose, due to a superior insulin stabilization and bioactivity. Conclusions: The freezing process may be detrimental to the structure of protein loaded into nanoparticles, with negative consequences to bioactivity. The co-encapsulation of cryoprotectants mitigated the freezing stresses with benefits to protein bioactivity. [ABSTRACT FROM AUTHOR]

Purpose: Nanostructured Lipid Carriers (NLCs) loading oxaprozin were developed to address an effective drug packaging and targeted delivery, improving the drug pharmacokinetics and pharmacodynamics properties and avoiding the local gastric side-effects. Macrophages actively phagocyte particles with sizes larger than 200 nm and, when activated, over-express folate beta receptors - features that in the case of this work constitute the basis for passive and active targeting strategies. Methods: Two formulations containing oxaprozin were developed: NLCs with and without folate functionalization. In order to target the macrophages folate receptors, a DSPE-PEG-FA conjugate was synthesized and added to the NLCs. Results: These formulations presented a relatively low polydispersity index (approximately 0.2) with mean diameters greater than 200 nm and zeta potential inferior to −40 mV. The encapsulation efficiency of the particles was superior to 95% and the loading capacity was of 9%, approximately. The formulations retained the oxaprozin release in simulated gastric fluid (only around 10%) promoting its release on simulated intestinal fluid. MTT and LDH assays revealed that the formulations only presented cytotoxicity in Caco-2 cells for oxaprozin concentrations superior to 100 μM. Permeability studies in Caco-2 cells shown that oxaprozin encapsulation did not interfered with oxaprozin permeability (around 0.8 × 10 cm/s in simulated intestinal fluid and about 1.45 × 10 cm/s in PBS). Moreover, in RAW 264.7 cells NLCs functionalization promoted an increased uptake over time mainly mediated by a caveolae uptake mechanism. Conclusions: The developed nanoparticles enclose a great potential for oxaprozin oral administration with significant less gastric side-effects. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX) and superparamagnetic iron oxide nanoparticles (SPIONs) were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than -16 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM) photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 μg/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications. [ABSTRACT FROM AUTHOR]

Wound care has been clinically demanding due to inefficacious treatment that represents an economic burden for healthcare systems. In Europe, approximately 7 million people are diagnosed with untreated wounds, leading to a cost between 6.000€ and 10.000€ per patient/year. In the United States of America, 1.5 million people over 65 years old suffer from chronic wounds. A promising therapeutic strategy is the use of exogenous growth factors because they are decreased at the wound site, limiting the recovery of the skin. Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. The aim of this review is to perform a standing point about a promising strategy to treat different types of wounds by the topical delivery of insulin-loaded nanocarriers. [ABSTRACT FROM AUTHOR]

A series of unique PLGA-chitosan hybrid polymers with tailored and tunable physicochemical characteristics were obtained with two different synthetic methods: solid-phase synthesis on a film or in solution chemical reaction with polycaprolactone as intermediate. These dependent variables were affected by the chitosan, alginate, and calcium chloride concentrations, while zeta potential depended only on the alginate and calcium chloride concentrations. Polydimethylsiloxane molds were used to obtain poly(vinyl alcohol)-poly(vinyl pyrrolidone) microneedles to carry the freeze-dried PLP-loaded PLGA nanoparticles. Shin et al. developed PLGA nanoparticles as siRNA carriers to overcome ROS/oxidative stress-induced chondrocyte damage in osteoarthritis [[5]]. [Extracted from the article]

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages' activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications. [ABSTRACT FROM AUTHOR]

This work aims to optimize and assess the potential use of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), as drug delivery systems of rifapentine (RPT) for the treatment of tuberculosis (TB). A Box–Behnken design was used to increase drug encapsulation efficiency (EE) and loading capacity (LC) of RPT-loaded NLCs. The optimized nanoparticles were fully characterized, and their effect on cell viability was assessed. The quality-by-design approach allowed the optimization of RPT-loaded NLCs with improved EE and LC using the minimum of experiments. Analyses of variance were indicative of the validity of this model to optimize this nanodelivery system. The optimized NLCs had a mean diameter of 242 ± 9 nm, polydispersity index <0.2, and a highly negative zeta potential. EE values were higher than 80%, and differential scanning calorimetry analysis enabled the confirmation of the efficient encapsulation of RPT. Transmission electron microscopy analysis showed spherical nanoparticles, uniform in shape and diameter, with no visible aggregation. Stability studies indicated that NLCs were stable over time. No toxicity was observed in primary human macrophage viability for nanoparticles up to 1000 μg mL−1. Overall, the optimized NLCs are efficient carriers of RPT and should be considered for further testing as promising drug delivery systems to be used in TB treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cutaneous melanoma (CM) is a multifactorial and heterogeneous disease. • Understanding CM molecular biology is crucial to design targeted nanomedicines. • Biomimetic nanovaccines may constitute future strategies for CM immunotherapy. • Magnetic nanosystems can be used as CM theranostic platforms. • Different advanced CM therapeutic modalities can be combined using nanosystems. Cutaneous melanoma (CM) is a multifactorial disease whose treatment still presents challenges: the rapid progression to advanced CM, which leads to frequent recurrences even after surgical excision and, notably, the low response rates and resistance to the available therapies, particularly in the case of unresectable metastatic CM. Thereby, alternative innovative therapeutic approaches for CM continue to be searched. In this review we discuss relevant preclinical research studies, and provide a broad-brush analysis of patents and clinical trials which involve the application of nanotechnology-based delivery systems in CM therapy. Nanodelivery systems have been developed for the delivery of anticancer biomolecules to CM, which can be administered by different routes. Overall, nanosystems could promote technological advances in several therapeutic modalities and can be used in combinatorial therapies. Nevertheless, the results of these preclinical studies have not been translated to clinical applications. Thus, concerted and collaborative research studies involving basic, applied, translational, and clinical scientists need to be performed to allow the development of effective and safe nanomedicines to treat CM. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection is one of the major risk factors for gastric cancer development. Available antibiotic-based treatments not only fail in around 20% of patients but also have a severe negative impact on the gut microbiota. Recently, we demonstrated that nanostructured lipid carriers (NLC), even without any drug loaded, are bactericidal against H. pylori at low concentrations. This work aims to clarify NLC mode of action and to evaluate if their bactericidal effect is specific to H. pylori without affecting bacteria from microbiota. NLC were produced by hot homogenization followed by ultrasonication method, using Precirol®ATO5 and Miglyol®812 as lipids and Tween®60 as a surfactant. NLC were able to eradicate H. pylori without affecting the other tested bacteria ( Lactobacillus, E. coli, S. epidermidis and S. aureus). Bioimaging assays demonstrated that NLC rapidly bind to and cross the H. pylori bacterial membrane, destabilizing and disrupting it, which leads to leakage of the cytoplasmic contents and consequent bacterial death. In an era where efficient alternatives to antibiotics are urgent, NLC are an interesting route to be explored in the quest for new antibiotic-free therapies to fight H. pylori infection. [ABSTRACT FROM AUTHOR]

The aim of this work was to use annealing as a tool to optimize the lyophilization cycle by decreasing its duration time, and simultaneously preserve the stability of poly(lactic- co -glycolic acid) nanoparticles and with upmost importance, maintain the structural stability of loaded insulin, used as model therapeutic protein. The contribution of a cryoprotectant in this preservation process was also evaluated. Insulin-loaded nanoparticles co-encapsulated with and without trehalose as cryoprotectant were produced, resulting in a particle size of about 250–300 nm, a PdI around 0.25 and a zeta potential in the range of −20 to −24 mV. The insulin association efficiency was higher than 90%, and the loading capacity was of 11–12%. The use of annealing allowed the decrease of duration time of primary drying in about 38%, representing a global decrease of lyophilization time of around 26%. The residual moisture content of all lyophilizates was around 1%, and the reconstitution of lyophilizates obtained using annealing was even faster than those without annealing. The co-encapsulated trehalose better preserved the nanoparticle size throughout the lyophilization process using annealing, compared to formulation containing no cryoprotectant. Fourier-transform infrared spectroscopy showed that the trehalose-containing nanoparticles presented higher insulin structural maintenance, compared to nanoparticles without cryoprotectant, presenting an insulin structural maintenance of 85.3 ± 0.7% and 86.0 ± 1.0% for annealing and no annealing, respectively. This formulation also presented the closest structural similarity with native insulin. Interestingly, the structural features of insulin loaded into nanoparticles upon lyophilization with and without annealing were practically identical, showing that annealing had no detrimental effect in insulin structure. Circular dichroism and fluorescence spectroscopy confirmed these results. Overall, this work gave rise to the importance of annealing in decreasing the duration time of lyophilization of protein-loaded poly(lactic- co -glycolic acid) nanoparticles, and simultaneously ensuring the stability of the carrier and loaded protein. [ABSTRACT FROM AUTHOR]

The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol at 10% (w/v). Insulin-loaded PLGA nanoparticles with co-encapsulated lyoprotectants achieved a mean particle size of 386–466 nm, and a zeta potential ranging between −34 and −38 mV, dependent on the lyoprotectant used. Formulations had association efficiencies and loading capacities of 85–91% and 10–12%, respectively. The lyophilization process increased the colloidal stability of nanoparticles, and maintained their spherical shape and smooth surface, particularly in presence of lyoprotectants. XRPD revealed that the lyophilizates of nanoparticles with co-encapsulated lyoprotectants were amorphous, whereas formulations with externally added lyoprotectants, except trehalose, showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved insulin structure upon lyophilization with a spectral area overlap of 82–87%, compared to only 72% in lyoprotectant absence. These results were confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol achieved 83%, 69%, 70%, 77% and 74%, respectively after 48 h. In contrast, formulations added with those lyoprotectants prior lyophilization showed a lower release rate not higher than 60% after 48 h. This work gives rise to a different promising strategy of co-encapsulating lyoprotectants and therapeutic proteins, to better stabilize protein structure upon lyophilization. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a high prevalence and one of the most severe and lethal diseases in the world. Insulin is commonly used to treat diabetes in order to give patients a better life condition. However, due to bioavailability problems, the most common route of insulin administration is the subcutaneous route, which may present patients compliance problems to treatment. The oral administration is thus considered the most convenient alternative to deliver insulin, but it faces important challenges. The low stability of insulin in the gastrointestinal tract and low intestinal permeation, are problems to overcome. Therefore, the encapsulation of insulin into polymer-based nanoparticles is presented as a good strategy to improve insulin oral bioavailability. In the last years, different strategies and polymers have been used to encapsulate insulin and deliver it orally. Polymers with distinct properties from natural or synthetic sources have been used to achieve this aim, and among them may be found chitosan, dextran, alginate, poly(γ-glutamic acid), hyaluronic acid, poly(lactic acid), poly(lactide-co-glycolic acid), polycaprolactone (PCL), acrylic polymers and polyallylamine. Promising studies have been developed and positive results were obtained, but there is not a polymeric-based nanoparticle system to deliver insulin orally available in the market yet. There is also a lack of long term toxicity studies about the safety of the developed carriers. Thus, the aims of this review are first to provide a deep understanding on the oral delivery of insulin and the possible routes for its uptake, and then to overview the evolution of this field in the last years of research of insulin-loaded polymer-based nanoparticles in the academic and industrial fields. Toxicity concerns of the discussed nanocarriers are also addressed. [ABSTRACT FROM AUTHOR]

This study aims to monitor the secondary structure behaviour of insulin when it is encapsulated into solid lipid nanoparticles (SLN), under the influence of several critical processing parameters. Insulin was used as a therapeutic protein model. Physicochemical properties of insulin-loaded SLN (Ins-SLN) were assessed, with special focus on the insulin secondary structure after its encapsulation into SLN and after freeze-drying using different cryoprotectants (glucose, fructose and sorbitol). Additionally, a 6-month stability study was performed to evaluate the maintenance of insulin secondary structure over time at different storage conditions (4°C/60% RH, 25°C/60% RH, 40°C/75% RH). Ins-SLN were successfully produced with a mean and narrow particle size around 400nm, zeta potential around ?13mV, an insulin association efficiency of 84%. Physical–chemical properties of SLN were maintained after freeze-drying. FTIR results showed that encapsulated insulin maintained a native-like structure in a degree of similarity around 92% after production, and 84% after freeze-drying. After 6 months, freeze-dried Ins-SLN without cryoprotectant stored at 40°C/75% RH presented the same degree of structure preservation and morphology. Results revealed that insulin structure can be significantly protected by SLN matrix itself, without a cryoprotectant agent, even using a non-optimized freeze-drying process, and under the harsher storage conditions. Multivariable experimental settled the process parameters to fit with the desired product quality attributes regarding protein and nanoparticle stability. [ABSTRACT FROM AUTHOR]

• Lipid nanoparticles coated with chitosan by association method show effective mucoadhesive profile. • Lipid nanoparticles promotes the controlled release of the drug in mucus layer. • Presence of chitosan promotes higher mucoadhesive properties and permeability. • Lipid nanoparticles loaded with rifampicin has potential to improve TB treatment. This work proposes the development and characterization of solid lipid nanoparticles (SLNs) loaded with rifampicin (RIF) aiming to enhance mucoadhesion of the SLNs and consequently internalization by the alveolar macrophages (AMs). The lipid nanoparticles (NPs) were characterized and the results showed that the NPs obtained present a spherical or a starry shape with diameter around 250−500 nm, a monodisperse population, with zeta potential between −31 mV for uncoated SLNs and +33 mV for coated SLNs. The drug EE was approximately 90 % and the loading capacity (LC) 4.5 %. The SLNs coated with chitosan by the association method (aC-SLNs) show an effective mucoadhesive profile, verified by the turdimetry and surface loading method, corroborated with the cellular assays. The presence of chitosan in the aC-SLNs promotes higher mucoadhesive properties to the NPs and permeability in A549, suggesting that the safe aC-SLNs-RIF can be used as a promising drug delivery system for improving tuberculosis treatment. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX), an anti-neoplastic agent used for breast cancer treatment, has restricted clinical applications due to poor water solubility, non-specific targeting and adverse side effects. To overcome these limitations, MTX was co-encapsulated with an active-targeting platform known as superparamagnetic iron oxide nanoparticles (SPIONs) in a lipid-based homing system, nanostructured lipid carrier (NLC). This multi-modal therapeutic regime was successfully formulated with good colloidal stability, bio- and hemo-compatibility. MTX-SPIONs co-loaded NLC was time-dependent cytotoxic towards MDA-MB-231 breast cancer cell line with IC 50 values of 137 μg/mL and 12 μg/mL at 48 and 72 h, respectively. The MTX-SPIONs co-loaded NLC was internalized in the MDA-MB-231 cells via caveolae-mediated endocytosis in a time-dependent manner, and the superparamagnetic properties were sufficient to induce, under a magnetic field, a localized temperature increase at cellular level resulting in apoptotic cell death. In conclusion, MTX-SPIONs co-loaded NLC is a potential magnetic guiding multi-modal therapeutic system for the treatment of breast cancer. Unlabelled Image • Methotrexate was co-encapsulated with SPIONs in a lipid-based homing system. • The multifunctional lipid nanoparticles exhibited bio- and hemo-compatibility. • MTX-SPIONs co-loaded NLC was time-dependent cytotoxic towards breast cancer cells. • The NLCs were internalized in breast cancer cells via caveolae-mediated endocytosis. • MTX-SPIONs co-loaded NLC can act as magnetic guiding multi-modal therapeutic system. [ABSTRACT FROM AUTHOR]