Sugarcane Light-Colored Lignin: A Renewable Resource for Sustainable Beauty.

Lignin has emerged as a promising eco-friendly multifunctional ingredient for cosmetic applications, due to its ability to protect against ultraviolet radiation and its antioxidant and antimicrobial properties. However, its typical dark color and low water solubility limit its application in cosmetics. This study presents a simple process for obtaining light-colored lignin (LCLig) from sugarcane bagasse (SCB) alkaline black liquor, involving an oxidation treatment with hydrogen peroxide, followed by precipitation with sulfuric acid. The physico-chemical characterization, antioxidant and emulsifying potential of LCLig, and determination of its safety and stability in an oil-in-water emulsion were performed. A high-purity lignin (81.6%) with improved water solubility was obtained, as a result of the balance between the total aromatic phenolic units and the carboxylic acids. In addition, the antioxidant and emulsifying capacities of the obtained LCLig were demonstrated. The color reduction treatment did not compromise the safety of lignin for topical cosmetic applications. The emulsion was stable in terms of organoleptic properties (color, pH, and viscosity) and antioxidant activity over 3 months at 4, 25, and 40 °C.

Lignin from sugarcane bagasse as a prebiotic additive for poultry feed.

Diet is a crucial factor on health and well-being of livestock animals. Nutritional strengthening with diet formulations is essential to the livestock industry and animal perfor-mance. Searching for valuable feed additives among by-products may promote not only circular economy, but also functional diets. Lignin from sugarcane bagasse was proposed as a potential prebiotic additive for chickens and incorporated at 1 % (w/w) in commercial chicken feed, tested in two feed forms, namely, mash and pellets. Physico-chemical characterization of both feed types with and without lignin was performed. Also, the prebiotic potential for feeds with lignin was assessed by an in vitro gastrointestinal model and evaluated the impact on chicken cecal Lactobacillus and Bifidobacterium. As for the pellet's physical quality, there was a higher cohesion of the pellets with lignin, indicating a higher resistance to breakout and lignin decreases the tendency of the pellets for microbial contamination. Regarding the prebiotic potential, mash feed with lignin showed higher promotion of Bifidobacterium in comparison with mash feed without lignin and to pellet feed with lignin. Lignin from sugarcane bagasse has prebiotic potential as additive to chicken feed when supplemented in mash feed diets, presenting itself as a sustainable and eco-friendly alternative to chicken feed additives supplementation.

From sugarcane to skin: Lignin as a multifunctional ingredient for cosmetic application.

Lignin has been suggested as a promising candidate for cosmetic applications due to its remarkable potential to absorb ultraviolet rays and distinctive antioxidant activity. This study aims at evaluating the performance of lignin from sugarcane bagasse (SCB) as natural UV blocker, antioxidant, and pigment. Lignin was extracted from SCB, characterized and incorporated into a blemish balm (BB) cream. The biological potential, concretely, in vitro and in vivo sun protection factor (SPF) and in vitro UVA-PF, and safety were assessed. A high-purity SCB lignin (>92 %) was obtained by a mild alkaline extraction process. The results of cytotoxicity, mutagenicity, skin sensitization and in vivo acute cutaneous irritation demonstrated that SCB lignin is safe for topical applications. Lignin showed capacity to scavenge both ABTS and DPPH radicals, which were preserved after its incorporation into the cosmetic formulation. Notable results were achieved in terms of in vitro and in vivo SPF of 9.5 ± 2.9 and 9.6 ± 0.8, respectively. Furthermore, the tested lignin-based BB cream revealed a broad-spectrum UV protection (critical wavelength of 378 ± 0.5 nm). These results suggest SCB lignin as multifunctional and safe ingredient for use in cosmetic products.

Non-melanoma skin cancers: physio-pathology and role of lipid delivery systems in new chemotherapeutic treatments.

Non-melanoma carcinoma has high incidence rates and has two most common subtypes: basal cell carcinoma and squamous cell carcinoma. This type of carcinoma is usually not fatal; however, it can destroy sensory organs such as the nose, ears, and lips. The treatment of these injuries using non-invasive methods is thus strongly recommended. Some treatments for non-melanoma carcinoma are already well defined, such as surgery, cryosurgery, curettage and electrode section, and radiotherapy; however, these conventional treatments cause inflammation and scarring. In the non-surgical treatment of non-melanoma carcinoma, the topical administration of chemotherapeutic drugs contributes for an effective treatment with reduced side effects. However, the penetration of anticancer drugs in the deeper layers of the skin is required. Lipid delivery systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers) have been developed to overcome epidermal barrier of the skin and to allow the drugs to reach tumor cells. These lipid nanoparticles contribute to control the release profile of the loaded chemotherapeutic drugs, maintaining their stability and increasing death of tumor cells. In this review, the characteristics of non-melanoma carcinoma will be discussed, describing the main existing treatments, together with the contribution of lipid delivery systems as an innovative approach to increase the effectiveness of topical therapies for non-melanoma carcinomas.

Biomimetic Surface Topography from the Rubus fruticosus Leaf as a Guidance of Angiogenesis in Tissue Engineering Applications.

The promotion of angiogenesis is a fundamental step for efficient organ/tissue reconstitution and replacement. Thus, several strategies to promote vascularization of scaffolds were studied to satisfy this unsolved clinical need. The interface between cells and substrates is a determinant for the success of tissue engineering (TE) strategies. Substrate's topography is reported to play a key role in influencing endothelial cell behavior, namely, on its proliferation, metabolic activity, morphology, migration, and secretion of cytokines and chemokines. Therefore, surface topography of the biomaterial-based grafts is a crucial property that is considered in the development of a new TE approach. Herein, we hypothesize that the surface of Rubus fruticosus leaf plays a crucial role in driving angiogenesis since its architecture resembles the vascular structures at a biologically relevant size scale. For this, we produced biomimetic polycaprolactone (PCL) membranes (BpMs) replicating the surface topography of a R. fruticosus leaf by replica molding and nanoimprint lithography. Our results showed an enhanced performance in terms of proliferation of the human endothelial cell line on top of the BpM. Moreover, an asymmetric cellular spatial distribution among the surface of the BpM was observed. These cells seem to have higher density for longer time periods in the region that replicates the leaf veins. Finally, we assess the angiogenic capacity through a chick chorioallantoic membrane assay, revealing that BpMs are more prone to support angiogenesis than flat PCL membranes. We strongly believe that this strategy can bring new insights into developing TE strategies with an enhanced performance in terms of the vascular integration between the host and the scaffolds implanted.

Physicochemical and biopharmaceutical aspects influencing skin permeation and role of SLN and NLC for skin drug delivery.

The skin is a complex and multifunctional organ, in which the static versus dynamic balance is responsible for its constant adaptation to variations in the external environment that is continuously exposed. One of the most important functions of the skin is its ability to act as a protective barrier, against the entry of foreign substances and against the excessive loss of endogenous material. Human skin imposes physical, chemical and biological limitations on all types of permeating agents that can cross the epithelial barrier. For a molecule to be passively permeated through the skin, it must have properties, such as dimensions, molecular weight, pKa and hydrophilic-lipophilic gradient, appropriate to the anatomy and physiology of the skin. These requirements have limited the number of commercially available products for dermal and transdermal administration of drugs. To understand the mechanisms involved in the drug permeation process through the skin, the approach should be multidisciplinary in order to overcome biological and pharmacotechnical barriers. The study of the mechanisms involved in the permeation process, and the ways to control it, can make this route of drug administration cease to be a constant promise and become a reality. In this work, we address the physicochemical and biopharmaceutical aspects encountered in the pathway of drugs through the skin, and the potential added value of using solid lipid nanoparticles (SLN) and nanostructured lipid vectors (NLC) to drug permeation/penetration through this route. The technology and architecture for obtaining lipid nanoparticles are described in detail, namely the composition, production methods and the ability to release pharmacologically active substances, as well as the application of these systems in the vectorization of various pharmacologically active substances for dermal and transdermal applications. The characteristics of these systems in terms of dermal application are addressed, such as biocompatibility, occlusion, hydration, emollience and the penetration of pharmacologically active substances. The advantages of using these systems over conventional formulations are described and explored from a pharmaceutical point of view.

Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection.

A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic ß-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive ß-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal-regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.

Comparison of antiproliferative effect of epigallocatechin gallate when loaded into cationic solid lipid nanoparticles against different cell lines.

Several therapeutic properties have been attributed to epigallocatechin gallate (EGCG), a phytopharmaceutical polyphenol with antioxidant and antiproliferative activity. EGCG is, however, very prone to oxidation in aqueous solutions which changes its bioactive properties. Its loading in nanoparticles has been proposed to reduce its degradation while increasing its in vivo efficacy. The aim of this study was to compare the antiproliferative effect of EGCG before and after its loading in solid lipid nanoparticles (SLNs), against five different cell lines (Caco-2, HepG2, MCF-7, SV-80 and Y-79). EGCG produced concentration- and time-dependent antiproliferative effect, with efficacy dependent on the cell line. The order of potency was: MCF-7>SV-80>HepG2>Y-79>Caco-2, for 24 h exposure (MCF-7 IC50=58.60 ± 3.29 µg/mL; Caco-2 IC50>500.00 µg/mL). To the best of our knowledge this is the first study reporting EGCG antiproliferative effect in SV-80 and Y-79 cells. DDAB-SLN physicochemical properties (size ∼134 nm; PI∼0.179; ZP ∼+28mV) were only slightly modified with EGCG loading (EGCG-DDAB-SLN: ∼144 nm; PI∼0.160; ZP ∼+26mV). EGCG loading in SLN, only slightly increases the EGCG antiproliferative effect in MCF-7 and SV-80 cells. SLN exhibited intrinsic toxicity, attributed to the surfactant used in its production. From the obtained results, the biocompatibility of blank SLN must be also considered when testing the efficacy of loaded phytopharmaceutics.

The Influence of Polysaccharide Coating on the Physicochemical Parameters and Cytotoxicity of Silica Nanoparticles for Hydrophilic Biomolecules Delivery.

The present work reports the effect of polysaccharides (chitosan and sodium alginate) on silica nanoparticles (SiNP) for hydrophilic molecules delivery taking insulin as model drug. The influence of tetraethyl orthosilicate (TEOS) and homogenization speed on SiNP properties was assessed by a 22 factorial design achieving as optimal parameters: 0.43 mol/L of TEOS and homogenization speed of 5000 rpm. SiNP mean particle size (Z-Ave) was of 256.6 nm and polydispersity index (PI) of 0.218. SiNP coated with chitosan (SiNP-CH) or sodium alginate (SiNP-SA) increased insulin association efficacy; reaching 84.6% (SiNP-SA) and 90.8% (SiNP-CH). However, coated SiNP released 50%-60% of the peptide during the first 45 min at acidic environment, while uncoated SiNP only released 30%. Similar results were obtained at pH 6.8. The low Akaike's (AIC) values indicated that drug release followed Peppas model for SiNP-SA and second order for uncoated SiNP and SiNP-CH (pH 2.0). At pH 6.8, the best fitting was Boltzmann for Ins-SiNP. However, SiNP-CH and SiNP-SA showed a first-order behavior. Cytotoxicity of nanoparticles, assessed in Caco-2 and HepG2 cells, showed that 100 to 500 µg/mL SiNP-CH and SiNP-SA slightly decreased cell viability, comparing with SiNP. In conclusion, coating SiNP with selected polysaccharides influenced the nanoparticles physicochemical properties, the insulin release, and the effect of these nanoparticles on cell viability.

Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line.

The aim of this work is development of a nontoxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimesulide (NiM) by a 22 factorial design. The optimized formulation was composed of 10 wt% of glyceryl behenate and 2.5 wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1 ± 0.114 nm, with a polydispersity index (PI) of 0.171 ± 0051 and zeta potential nearly neutral (-3.10 ± 0.166 mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25 °C for a period of 15 days, whereas at 4 °C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab®, showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24 h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100 µg/mL) up to 48 hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1 ± 36.63 nm (PI 0.491 ± 0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.

The Role of Natural-Based Biomaterials in Advanced Therapies for Autoimmune Diseases.

Autoimmune diseases (ADs) constitute a heterogeneous group of more than 100 pathophysiological conditions in which an immune response against the self is observed. The incidence and prevalence of these chronic diseases are increasing with inherently high social and economic impacts. The currently available therapies generally focus on reducing the activity of the immune system and, therefore, can present severe side effects such as enhanced patient susceptibility to opportunistic infections. Advanced therapies emerged as promising treatments and with real curative potential for ADs. Additionally, the use of natural polymers to engineer gene therapies, cell therapies and/or tissue-engineered medicinal products presents specific advantages. Natural polymers present higher affinity with biological systems than synthetic polymers, and frequently have a chemical structure and motifs similar to those existing in the extracellular matrix of the tissues. They also have good biological performance, making them very strong candidates for advanced therapy medicinal products. This review discusses the therapeutic advances and provides demonstrative examples of the role of natural-based biomaterials for the development of advanced therapies for ADs.

Biopharmaceutical evaluation of epigallocatechin gallate-loaded cationic lipid nanoparticles (EGCG-LNs): In vivo, in vitro and ex vivo studies.

Cationic lipid nanoparticles (LNs) have been tested for sustained release and site-specific targeting of epigallocatechin gallate (EGCG), a potential polyphenol with improved pharmacological profile for the treatment of ocular pathologies, such as age-related macular edema, diabetic retinopathy, and inflammatory disorders. Cationic EGCG-LNs were produced by double-emulsion technique; the in vitro release study was performed in a dialysis bag, followed by the drug assay using a previously validated RP-HPLC method. In vitro HET-CAM study was carried out using chicken embryos to determine the potential risk of irritation of the developed formulations. Ex vivo permeation profile was assessed using rabbit cornea and sclera isolated and mounted in Franz diffusion cells. The results show that the use of cationic LNs provides a prolonged EGCG release, following a Boltzmann sigmoidal profile. In addition, EGCG was successfully quantified in both tested ocular tissues, demonstrating the ability of these formulations to reach both anterior and posterior segment of the eye. The pharmacokinetic study of the corneal permeation showed a first order kinetics for both cationic formulations, while EGCG-cetyltrimethylammonium bromide (CTAB) LNs followed a Boltzmann sigmoidal profile and EGCG-dimethyldioctadecylammonium bromide (DDAB) LNs a first order profile. Our studies also proved the safety and non-irritant nature of the developed LNs. Thus, loading EGCG in cationic LNs is recognised as a promising strategy for the treatment of ocular diseases related to anti-oxidant and anti-inflammatory pathways.

Ocular Drug Delivery - New Strategies for Targeting Anterior and Posterior Segments of the Eye.

The ocular delivery of drugs encounters several limitations because of the dynamic and static barriers of the human's eye anatomy and physiology. The poor bioavailability of drugs are mainly related to the topical administration, i.e. eye drops which is the most common drug dosage form for the treatment of eye pathologies. Precorneal factors and drug limitations related to its solubility and susceptibility for physicochemical degradation could be the main reasons for the poor permeation and uptake in the ocular mucosa. Pathologies affecting the anterior and posterior segment of the eye are thereafter difficult to be treated and, given the chronic and degenerative nature of some of these injuries, it is crucial to improve drugs therapeutic effect. Nanotechnology-based delivery systems could be a suitable approach to overcome these limitations. Some of the most important colloidal systems are highlighted in this review, such as the use of mucoadhesive polymers, prodrugs, nanogels, liposomes, microemulsions, lipid and polymeric nanoparticles, cyclodextrins, dendrimers and nanocrystals, along with their clinical and therapeutic relevance for the administration of drugs for ocular delivery.

Hydrophilic Polymers for Modified-Release Nanoparticles: A Review of Mathematical Modelling for Pharmacokinetic Analysis.

Hydrophilic polymers are the most common group of polymers used in the preparation of modifiedrelease drug delivery systems. This is due to their versatility, low cost, high production yield, as well as easy manufacturing and adequate in vitro/in vivo correlation. In normal physiological conditions, the matrix controls the release of the loaded drug over time through a process of diffusion and/or erosion of the matrix, depending on its physicochemical composition. This is particularly relevant when describing the pharmacokinetic profile of nanosized drug delivery systems (nanoparticles). The use of mathematical models became an important tool to characterize the pharmacokinetics of drugs loaded in nanoparticles to improve the drug bioavailability and to establish bioequivalence. Therefore, the drug release profile can be predicted by a minimum number of experimental studies, since the mathematical equations reveal the dissolution rate of the drug loaded in the hydrophilic matrix. The present paper discusses the use of mathematical models when developing modified-release drug delivery systems of nanometer size composed of hydrophilic polymers.

Effect of mucoadhesive polymers on the in vitro performance of insulin-loaded silica nanoparticles: Interactions with mucin and biomembrane models.

The present paper focuses on the development and characterization of silica nanoparticles (SiNP) coated with hydrophilic polymers as mucoadhesive carriers for oral administration of insulin. SiNP were prepared by sol-gel technology under mild conditions and coated with different hydrophilic polymers, namely, chitosan, sodium alginate or poly(ethylene glycol) (PEG) with low and high molecular weight (PEG 6000 and PEG 20000) to increase the residence time at intestinal mucosa. The mean size and size distribution, association efficiency, insulin structure and insulin thermal denaturation have been determined. The mean nanoparticle diameter ranged from 289 nm to 625 nm with a PI between 0.251 and 0.580. The insulin association efficiency in SiNP was recorded above 70%. After coating, the association efficiency of insulin increased up to 90%, showing the high affinity of the protein to the hydrophilic polymer chains. Circular dichroism (CD) indicated that no conformation changes of insulin structure occurred after loading the peptide into SiNP. Nano-differential scanning calorimetry (nDSC) showed that SiNP shifted the insulin endothermic peak to higher temperatures. The influence of coating on the interaction of nanoparticles with dipalmitoylphosphatidylcholine (DPPC) biomembrane models was also evaluated by nDSC. The increase of ΔH values suggested a strong association of non-coated SiNP and those PEGylated nanoparticles coated with DPPC polar heads by forming hydrogen bonds and/or by electrostatic interaction. The mucoadhesive properties of nanoparticles were examined by studying the interaction with mucin in aqueous solution. SiNP coated with alginate or chitosan showed high contact with mucin. On the other hand, non-coated SiNP and PEGylated SiNP showed lower interaction with mucin, indicating that these nanoparticles can interdiffuse across mucus network. The results of the present work provide valuable data in assessing the in vitro performance of insulin-loaded SiNP coated with mucoadhesive polymers.

Current nanotechnology approaches for the treatment and management of diabetic retinopathy.

Diabetic retinopathy (DR) is a consequence of diabetes mellitus at the ocular level, leading to vision loss, and contributing to the decrease of patient's life quality. The biochemical and anatomic abnormalities that occur in DR are discussed in this review to better understand and manage the development of new therapeutic strategies. The use of new drug delivery systems based on nanoparticles (e.g. liposomes, dendrimers, cationic nanoemulsions, lipid and polymeric nanoparticles) is discussed along with the current traditional treatments, pointing out the advantages of the proposed nanomedicines to target this ocular disease. Despite the multifactorial nature of DR, which is not entirely understood, some strategies based on nanoparticles are being exploited for a more efficient drug delivery to the posterior segment of the eye. On the other hand, the use of some nanoparticles also seems to contribute to the development of DR symptoms (e.g. retinal neovascularization), which are also discussed in light of an efficient management of this ocular chronic disease.

Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies.

The present work aimed at studying the interaction between insulin and SiNP surfaced with mucoadhesive polymers (chitosan, sodium alginate or polyethylene glycol) and the evaluation of their biocompatibility with HepG2 and Caco-2 cell lines, which mimic in vivo the target of insulin-loaded nanoparticles upon oral administration. Thus, a systematic physicochemical study of the surface-modified insulin-silica nanoparticles (Ins-SiNP) using mucoadhesive polymers has been described. The surfacing of nanoparticle involved the coating of silica nanoparticles (SiNP) with different mucoadhesive polymers, to achieve high contact between the systems and the gut mucosa to enhance the oral insulin bioavailability. SiNP were prepared by a modified Stöber method at room temperature via hydrolysis and condensation of tetraethyl orthosilicate (TEOS). Interaction between insulin and nanoparticles was assessed by differential scanning calorimetry (DSC), X-ray and Fourier-transform infrared (FTIR) studies. The high efficiency of nanoparticles' coating resulted in more stable system. FTIR spectra of insulin-loaded nanoparticles showed amide absorption bands which are characteristic of α-helix content. In general, all developed nanoparticles demonstrated high biocompatible, at the tested concentrations (50-500 µg/mL), revealing no or low toxicity in the two human cancer cell lines (HepG2 and Caco-2). In conclusion, the developed insulin-loaded SiNP surfaced with mucoadhesive polymers demonstrated its added value for oral administration of proteins.

Physicochemical characterization of epigallocatechin gallate lipid nanoparticles (EGCG-LNs) for ocular instillation.

The encapsulation of epigallocatechin gallate (EGCG) in lipid nanoparticles (LNs) could be a suitable approach to avoid drug oxidation and epimerization, which are common processes that lead to low bioavailability of the drug limiting its therapeutic efficacy. The human health benefits of EGCG gained much interest in the pharmaceutical field, and so far there are no studies reporting its encapsulation in LNs. The purpose of this study has been the development of an innovative system for the ocular delivery of EGCG using LNs as carrier for the future treatment of several diseases, such as dry eye, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy and macular oedema. LNs dispersions have been produced by multiple emulsion technique and previously optimized by a factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, two distinct cationic lipids were used, namely, cetyltrimethylammonium bromide (CTAB) and dimethyldioctadecylammonium bromide (DDAB). EGCG has been successfully loaded in the LNs dispersions and the nanoparticles analysis over 30 days of storage time predicted a good physicochemical stability. The particles were found to be in the nanometer range (<300 nm) and all the evaluated parameters, namely pH, osmolarity and viscosity, were compatible to the ocular administration. The evaluation of the cationic lipid used was compared regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. The results show that different lipids lead to different characteristics mainly associated with the acyl chain composition, i.e. double lipid shows to have influence in the crystallization and stability. Despite the recorded differences between DTAB and DDAB, both cationic LNs seem to fit the parameters for ocular drug delivery.

Validation of a high performance liquid chromatography method for the stabilization of epigallocatechin gallate.

Epigallocatechin gallate (EGCG) is a green tea catechin with potential health benefits, such as anti-oxidant, anti-carcinogenic and anti-inflammatory effects. In general, EGCG is highly susceptible to degradation, therefore presenting stability problems. The present paper was focused on the study of EGCG stability in HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) medium regarding the pH dependency, storage temperature and in the presence of ascorbic acid a reducing agent. The evaluation of EGCG in HEPES buffer has demonstrated that this molecule is not able of maintaining its physicochemical properties and potential beneficial effects, since it is partially or completely degraded, depending on the EGCG concentration. The storage temperature of EGCG most suitable to maintain its structure was shown to be the lower values (4 or -20 °C). The pH 3.5 was able to provide greater stability than pH 7.4. However, the presence of a reducing agent (i.e., ascorbic acid) was shown to provide greater protection against degradation of EGCG. A validation method based on RP-HPLC with UV-vis detection was carried out for two media: water and a biocompatible physiological medium composed of Transcutol®P, ethanol and ascorbic acid. The quantification of EGCG for purposes, using pure EGCG, requires a validated HPLC method which could be possible to apply in pharmacokinetic and pharmacodynamics studies.

Nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) for retinyl palmitate: effect on skin permeation.

The aim of this study was to develop biocompatible lipid-based nanocarriers for retinyl palmitate (RP) to improve its skin delivery, photostability and biocompatibility, and to avoid undesirable topical side effects. RP loaded nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) were characterized in terms of size, surface electrical charge, pH, drug encapsulation efficiency and morphology. Spherical-shaped nanocarriers with a negatively charged surface (>|40|mV) and mean size lower than 275 nm were produced with adequate skin compatibility. The rheological properties showed that aqueous dispersions of SLNs followed a non-Newtonian behavior, pseudoplastic fluid adjusted to Herschel-Bulkley equation, whereas LPs and NEs exhibited a Newtonian behavior. SLNs offered significantly better photoprotection than LPs and NEs for RP. The cumulative amount of drug permeated through human skin at the end of 38 h was 6.67 ± 1.58 µg, 4.36 ± 0.21 µg and 3.64 ± 0.28 µg for NEs, LPs and SLNs, respectively. NEs flux was significantly higher than SLNs and LPs: NEs (0.37 ± 0.12 µg/h) > LPs (0.15 ± 0.09 µg/h) > SLNs (0.10 ± 0.05 µg/h). LPs offered significant higher skin retention than NEs and SLNs. Finally, even though all developed nanocarriers were found to be biocompatible, according to histological studies, NE was the system that most disrupted the skin. These encouraging findings can guide in proper selection of topical carriers among the diversity of available lipid-based nanocarriers, especially when a dermatologic or cosmetic purpose is desired.