Development Of Nanostructured Lipid Carriers Research Articles

Preparation and in vitro characterization studies of astaxanthin-loaded nanostructured lipid carriers with antioxidant properties.

The purpose of this study was to evaluate the astaxanthin-loaded nanostructured lipid carriers (ASX-NLC) prepared using a high-pressure homogenization transport system for local application of astaxanthin. Dynamic light scattering (DLS) and X-ray diffraction (XRD) were used to study the effect of microencapsulation on the properties of ASX-NLC. The mean size of ASX-NLC was about 108.43 ± 0.26nm and PdI was 0.176 ± 0.002. The ASX-NLC had high encapsulation efficiency which was 95.69 ± 0.13%. Good light stability and temperature stability were shown at the ASX-NLC, indicating that the preparation process was feasible. The 2,2-diphenyl-1-pyridylohydrazinyl (DPPH) scavenging test showed that ASX-NLC could still play an antioxidant role. In vitro release studies showed that compared with an astaxanthin ethanol solution, an ASX-NLC could maintain astaxanthin release more effectively. In vitro permeation studies showed that ASX-NLC could increase astaxanthin retention in the skin. In conclusion, ASX-NLC could significantly enhance astaxanthin accumulation during dermal applications. The research results have important reference significance for local skin applications and provide a basis for the development of nanostructured lipid carriers. ASX-NLC might be suitable carriers for the local application of astaxanthin.

Development of nanostructured lipid carrier containing tea tree oil: Physicochemical properties and stability

Context: Tea tree oil (TTO) is an essential oil derived from Melaleuca alternifolia, with high antimicrobial and antifungal potential. Unfortunately, its topical antifungal efficacy is limited because it is volatile, thermolabile and easily oxidized. A formulation has been developed to overcome this problem by encapsulating TTO in a nanostructured lipid carrier (NLC). Aims: To determine the effect of the liquid to solid lipid ratio on the physicochemical properties and the stability of TTO-loaded NLC. Methods: Five formula of TTO-loaded NLCs were produced by high shear homogenization method and characterized according to their particle size, size distribution, polydispersity, zeta potential, thermal characteristics, X-ray diffraction, and terpinen-4-ol concentration. In addition, a stability study was conducted by observing its physical and chemical characteristics during storage in the refrigerator (4 ± 2°C) and at room temperature (27 ± 2°C) for six months. Results: The resulting TTO-loaded NLC had an average droplet size under 400 nm. The particle size increases with increasing amount of liquid lipid in the formula. There were insignificant changes in organoleptic properties, polydispersity index, zeta potential and terpinene-4-ol concentration during stability study for six months. However, the particle size slightly increased during the six months of storage. Furthermore, the NLC 3, which formulated with a 25:95 ratio liquid to solid lipid, was be chosen as the best formula, since it demonstrated the best physicochemical characteristic and stability. Conclusions: TTO-loaded NLC with good physicochemical characteristics and stability has been successfully developed. In addition, NLC 3 is considered as the best NLC formula, which exhibits characteristics and stability that meet the requirements.

Development of NLC- based Sunscreen Gel of Lutein and its in-vitro and ex-vivo Characterisation

Background: In humans, Carotenoids are important in scavenging singlet oxygen and peroxyl radicals. Lutein has been demonstrated in multiple studies to help protect the skin from photodamage, as well as provide a variety of other health advantages. In the recent decade, the topi-cal use of Lutein as a new ultraviolet (UV) protectant, anti-stress, and blue light filter capable of protecting skin from photodamage has piqued cosmetic and pharmacological attention. Because Lutein is insoluble, it was integrated into nanocarriers for topical administration. Objective: The objective of this study was to formulate an NLC-based sunscreen gel of Lutein. Method: Nanostructured lipid carriers (NLC) were prepared by melt emulsion ultrafiltration tech-nique and were evaluated for particle size, zeta potential, polydispersity index (PDI), drug loading (DL), encapsulation efficacy (EE), and in vitro drug release. The optimised formula was incorpo-rated into a gel base and an in-vitro sun protection factor (SPF) was determined. Ex- vivo permea-tion study was performed on rat skin using a Franz diffusion cell. Cocoa butter and rose oil were chosen as solid and liquid lipids for NLC formulation. Results: The particle size, PDI, zeta potential, entrapment efficiency, and in vitro drug release of optimised formulation (NLC5) were found to be 81.64 nm, 0.463, -14.1mV, 79.90 %, and 89.86% respectively. The SPF value of the Lutein-NLC-loaded gel was found to be 27.524. The drug flux Jss from NLC gel was measured in the range of 0.07955 g/cm2/h. Conclusion: The investigation suggested lipid nanoparticles as a suitable carrier for Lutein to be delivered as sunscreen gel.

Nanostructured Lipid Carriers of Eperisone Hydrochloride using Quality By Design Approach

Objective: The current work involves formulation development of nanostructured lipid carrier (NLC) of eperisone hydrochloride (EPE) using quality by design (QbD) approach.
 Materials and Methods: Initial screening of solid and liquid lipids was performed based on the Hansen solubility parameters of EPE and the lipids and later confirmed using saturation solubility studies. The optimum formulation was identified using three-squared randomized full factorial design. High shear homogenization coupled with ultrasonication was used to prepare the NLCs. The effect of the independent variables on the dependent variables was analyzed using response surface graphs and ANOVA. The optimized formulation is characterized for mean particle size, zeta potential, entrapment efficiency, in vitro drug release and subjected to stability testing.
 Results and Discussion: Precirol® ATO 5, CapryolTM 90, and Pluronic® F127 are found to be ideal solid lipid, liquid lipid and surfactant respectively based on the initial screening. Amount of lipid mixture (X1) and the amount of surfactant (X2) were selected as independent variables and the entrapment efficiency (Y1), mean particle size (Y2) and zeta potential (Y3) were selected as dependent variables. The optimized NLC formulation has mean particle size of 175 nm, zeta potential -24.4 mV and entrapment efficiency of 78.64%. The in vitro drug release data suggested that the drug release follows Quasi-Fickian diffusion. The stability data showed that the NLCs are stable up to 3 months at refrigerated conditions.
 Conclusions: The Hansen solubility parameter approach coupled with QbD is a powerful tool for formulation of sustained release NLCs of highly soluble poorly soluble drugs.
 Keywords: Nanostructured lipid carrier, Solubility Parameters, Nanoparticles, Lipid based drug delivery, Quality by Design

Quality by design based development of nanostructured lipid carrier: a risk based approach

The aim of this review is to discuss the development of nanostructured lipid carrier (NLC) by the application of quality by design (QbD). QbD started with the evolution of the quality concept and slow adaptation of quality guidelines, which has now become a regulatory requirement. In this review, brief history and elements of QbD including risk assessment (RA) have been discussed followed by the design of experiments (DoEs) that acts as a tool to analyze the input whose variation can optimize the output with the desired goal. NLC is a versatile delivery system as researchers widely use it to administer therapeutics with different physicochemical properties. The surface of NLC can be modified, making it a suitable delivery system with targeting potential for therapeutics. Implementation of QbD provides a high-quality robust formulation that can consistently meet the patient’s requirement throughout its life cycle without compromising the safety and effectiveness of the drug and delivery system. This review discusses QbD concepts followed by the systematic development of NLC by the application of DoE. Process analytical technology (PAT) and six sigma concepts have also been included which can benefit in the development of optimized NLC.

Charge converting nanostructured lipid carriers containing a cell-penetrating peptide for enhanced cellular uptake

HypothesisThe aim of this study was the development of nanostructured lipid carriers (NLCs) decorated with a polycationic cell-penetrating peptide (CPP). A coating with polyphosphates (PP) enables charge conversion at target cells being triggered by the membrane bound enzyme intestinal alkaline phosphatase (IAP). ExperimentsThe CPP, stearyl-nona-L-arginine (R9SA) was obtained by solid phase synthesis. Formed nanocarriers were characterized regarding size, polydispersity index, zeta potential and charge conversion in the presence of IAP and on Caco-2 cells. The BCS class IV drug saquinavir (SQV) was loaded into NLCs in different concentrations. Mucus diffusion ability of the NLCs was evaluated by the rotating tube method. Furthermore, cellular uptake was evaluated on Caco-2 cells and endosomal escape properties were investigated using erythrocytes. FindingsAll NLCs were obtained in a size range between 146 nm and 152 nm and a polydispersity index of 0.2. Incubation of PP coated PP-R9SA-NLCs with IAP led to a charge conversion from −41.8 mV to 6.4 mV (Δ48.2 mV). After four hours of incubation with IAP, phosphate release reached a plateau, indicating a faster polyphosphate cleavage than on Caco-2. Drug load and encapsulation efficiency of SQV was obtained up to 80.6% and 46.5 µg/mg. Mucus diffusion was increasing in the following rank order: R9SA-NLCs < blank NLCs < PP-R9SA-NLCs. R9SA-NLCs and PP-R9SA-NLCs increased the cellular uptake 15.6- and 13.2-fold, respectively, compared to the control NLCs. Erythrocytes interaction study revealed enhanced endosomal escape properties for R9SA-NLCs and PP-R9SA-NLCs when incubated with IAP.

Formulation and Development of Nanostructured Lipid Carriers for a Poorly Water-Soluble Drug: Furosemide

Aim: Formulation, development and evaluation of solid lipid nanoparticles. Background: It was found that furosemide (FU) was a very potent drug but it fails to produce bioavailability due to its BCS class IV, so drug- cyclodextrin (CD)- nanostructured lipid carriers (NLC) will be an alternative to improve solubility and permeability as a result of this overall bioavaibility will be improved. Objective: To improve the solubility of drug by using complexation of cyclodextrin. Coating with the lipids (NLC) will improve the permeability of the drug. Methods: To generate solid Furosemide–cyclodextrin complexes (FU–CD), two distinct CDs and three different techniques were used. The co-evaporation (COE) Furosemide-β-cyclodextrinloaded NLC (FU– β-CD-COE-loaded NLC) was obtained by emulsification ultrasonic dispersion method. The selected batch was suitably characterized for particle size, polydispersity index, zeta potential, Entrapment efficiency, Drug release study, and permeability study. The crystallization of the drug in the furosemide cyclodextrin complex (FU–CD complex) and the co-evaporation Furosemide- β-cyclodextrin-loaded NLC (FU–β-CD-COE-loaded NLC) was investigated by differential scanning calorimetry (DSC). The in vitro release study was carried out. Results: The FU–β-CD-COE-loaded NLC and FU–HP-β-CD-COE-loaded NLC (Hydroxypropyl) presented a superior physicochemical property and were selected for further study. The in vitro release study of the above selected batches exhibited a higher dissolution rate in the pH 5.8 phosphate buffer than Furosemide suspension and FU–NLC. The permeability studies of abovementioned batches were compared with FU-Suspension. Conclusion: The novel formulation considerably enhanced the solubility and permeability of furosemide for oral delivery, and was successfully developed.

Anti-oxidant Containing Nanostructured Lipid Carriers of Ritonavir: Development, Optimization, and In Vitro and In Vivo Evaluations

Acquired immunodeficiency syndrome (AIDS) is a condition caused by the infection of a retrovirus namely, human immunodeficiency virus (HIV). Currently, highly active anti-retroviral therapy (HAART), a combination of anti-viral drugs belonging to different classes is considered to be effective in the management of HIV. Ritonavir, a protease inhibitor (PI), is one of the most important components of the HAART regimen. Because of its lower bioavailability and severe side effects, presently, ritonavir is not being used as a PI. However, this drug is being used as a pharmacokinetic boosting agent for other PIs such as lopinavir and in lower doses. The current study aimed to develop nanostructured lipid carriers (NLCs) encapsulating ritonavir to reduce its side effects and enhance oral bioavailability. Ritonavir-loaded NLCs were developed using a combination of two different solid lipids and liquid lipids. Alpha-tocopherol, a well-known anti-oxidant, was used as an excipient (liquid lipid) in the development of NLCs which were prepared using a simple hot-emulsion and ultrasonication method. Drug-excipient studies were performed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). QbD approach was followed for the screening and optimization of different variables. The developed NLCs were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). Furthermore, NLCs were studied for their in vitro drug release profile, and finally, pharmacokinetic parameters were determined using in vivo pharmacokinetic studies. The optimized NLC size was in the range of 273.9 to 458.7 nm, PDI of 0.314 to 0.480, ZP of −52.2 to − 40.9 mV, and EE in the range of 47.37 to 74.51%. From in vitro drug release, it was found that the release of drug in acidic medium was higher than phosphate buffer pH 6.8. Finally, in vivo pharmacokinetic studies revealed a 7-fold enhancement in the area under the curve (AUC) and more than 10-fold higher Cmax with the optimized formulation in comparison to pure drug suspension.Graphical

Development of nanostructured lipid carriers as a promising tool for methotrexate delivery: physicochemical and in vitro evaluation

The aim of the present study is to fabricate the stable nanostructured lipid carriers (NLCs) using biocompatible excipients for the encapsulation of Methotrexate (MTX), a chemotherapeutic agent for breast cancer treatment. MTX has restricted clinical applications owing to its low solubility, non-specific targeting and adverse side effects. Glyceryl Monostearate (GMS) and Miglyol 812 (MI1) were chosen as solid and liquid lipids, respectively, for the fabrication of NLCs, and the influence of variation of solid and liquid composition was investigated. The prepared NLCs exhibited long-term stability and spherical shape morphology as characterized by electron microscopy. The internal structure of fabricated NLCs was arranged into cubic crystalline as confirmed by small-angle X-ray scattering (SAXS) analysis. MTX's encapsulation efficiency of ∼85 ± 0.9%. and sustained in vitro release of MTX ∼ 52% ± 3.0 in 24 h was achieved. Classical molecular dynamics (MD) simulations were performed to study the structural stability of the MTX encapsulated NLCs. Hemolysis carried out on the NLCs showcased the biosafety of the formulation under the tolerance limit (<10%). Further, the MTT assay demonstrates that MTX-loaded NLCs exhibited toxicity against HeLa and MCF-7 cell lines as compared to blank NLCs. The finding demonstrates NLCs as promising vehicles for MTX delivery to address cancer. Communicated by Ramaswamy H. Sarma

Development of nanostructured lipid carriers loaded caffeic acid topical cream for prevention of inflammation in Wistar rat model

Development of nanostructured lipid carriers loaded caffeic acid topical cream for prevention of inflammation in Wistar rat model

Nanostructured Lipid Carriers as a Novel Strategy for Topical Antifungal Therapy.

Nanostructured lipid carriers (NLC) were developed as an alternative carrier system optimizing limitations found in topical treatments for superficial fungal infections, such as limited permeation through the skin. However, few published studies are focused on standardization and characterization of determinant variables of these lipid nanosystems' quality. Thus, this systematic review aims to compile information regarding the selection of lipids, surfactants, and preparation method that intimately relates to the final quality of this nanotechnology. For this, the search was carried with the following descriptors: 'nanostructured lipid carriers', 'topical', 'antifungal' separated by the Boolean operators 'and', present in the titles of the databases: Science Direct, Scopus and Pubmed. The review included experimental articles focused on the development of nanostructured lipid carriers targeted for topical application with antifungal activity, published from 2015 to 2021. Review articles, clinical studies, and studies on the development of other nanocarriers intended for other routes of administration were excluded from the study. The research included 26 articles, of which 58% were developed in India and Brazil, 53% published in the years 2019 and 2020. As for the selection of antifungal drugs incorporated into NLCs, the azole class had a preference over other classes, voriconazole being incorporated into 5 of the 26 developed NLC studied. It was also observed a predominance of medium chain triglycerides (MCT) as a liquid lipid and polysorbate 80 as a surfactant. Among other results, this review compiles the influences of each of the variables discussed in the quality parameters of NLCs, in order to guide future research involving the development of this technology. Graphical Abstract.

Development of a Mosquito Repellent Formulation Based on Nanostructured Lipid Carriers.

Arboviral diseases are a threat to global public health systems, with recent data suggesting that around 40% of the world’s population is at risk of contracting arboviruses. The use of mosquito repellents is an appropriate strategy to avoid humans coming into contact with vectors transmitting these viruses. However, the cost associated with daily applications of repellents can make their use unfeasible for the low-income populations that most need protection. Therefore, the development of effective formulations offers a way to expand access to this means of individual protection. Consequently, research efforts have focused on formulations with smaller quantities of active agents and sustained release technology, aiming to reduce re-applications, toxicity, and cost. The present study investigates the development of nanostructured lipid carriers (NLCs) loaded with a mixture of the compounds icaridin (synthetic) and geraniol (natural), incorporated in cellulose hydrogel. The NLCs were prepared by the emulsion/solvent evaporation method and were submitted to physicochemical characterization as a function of time (at 0, 15, 30, and 60 days). The prepared system presented an average particle size of 252 ± 5 nm, with encapsulation efficiency of 99% for both of the active compounds. The stability profile revealed that the change of particle size was not significant (p > 0.05), indicating high stability of the system. Rheological characterization of the gels containing NLCs showed that all formulations presented pseudoplastic and thixotropic behavior, providing satisfactory spreadability and long shelf life. Morphological analysis using atomic force microscopy (AFM) revealed the presence of spherical nanoparticles (252 ± 5 nm) in the cellulose gel matrix. Permeation assays showed low fluxes of the active agents through a Strat-M® membrane, with low permeability coefficients, indicating that the repellents would be retained on the surface to which they are applied, rather than permeating the tissue. These findings open perspectives for the use of hybrid formulations consisting of gels containing nanoparticles that incorporate repellents effective against arthropod-borne virus. These systems could potentially provide improvements considering the issues of effectiveness, toxicity, and safety.

Essential Oil-Loaded NLC for Potential Intranasal Administration.

Complementary and alternative medicines represent an interesting field of research on which worldwide academics are focusing many efforts. In particular, the possibility to exploit pharmaceutical technology strategies, such as the nanoencapsulation, for the delivery of essential oils is emerging as a promising strategy not only in Italy but also all over the world. The aim of this work was the development of nanostructured lipid carriers (NLC) for the delivery of essential oils (Lavandula, Mentha, and Rosmarinus) by intranasal administration, an interesting topic in which Italian contributions have recently increased. Essential oil-loaded NLC, projected as a possible add-on strategy in the treatment of neurodegenerative diseases, were characterized in comparison to control formulations prepared with Tegosoft CT and Neem oil. Homogeneous (polydispersity index, PDI < 0.2) nanoparticles with a small size (<200 nm) and good stability were obtained. Morphological and physical-chemical studies showed the formation of different structures depending on the nature of the liquid oil component. In particular, NLC prepared with Lavandula or Rosmarinus showed the formation of a more ordered structure with higher cytocompatibility on two cell lines, murine and human fibroblasts. Taken together, our preliminary results show that optimized positively charged NLC containing Lavandula or Rosmarinus can be proposed as a potential add-on strategy in the treatment of neurodegenerative diseases through intranasal administration, due to the well-known beneficial effects of essential oils and the mucoadhesive properties of NLC.

Raman Imaging and Chemometrics Evaluation of Natural and Synthetic Beeswaxes as Matrices for Nanostructured Lipid Carriers Development

Beeswaxes are interesting solid lipids for the development of nanostructured lipid carriers (NLC), and their origin can be either natural or synthetic. Due to this difference, their performance should be distinct and unstable formulations can be generated. The objective of this work was to investigate miscibility and structural changes (polymorphism) in pre-formulations (blends of solid and liquid lipids) using synthetic and natural beeswaxes in combination with copaiba oil (a natural liquid lipid), in the concentration range of 5.0 to 50.0% (w/w). Raman spectra were acquired over a region of 4 mm2 (mapping mode), dead pixels were removed using Independent Components Analysis (ICA) and Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) was then used to generate the images. Samples were analyzed at the initial time and after 3 months, using the Distributional Homogeneity Index (DHI) and standard deviation of the histograms. The pre-formulation containing synthetic beeswax showed different structural forms before and after melting, and structural changes over time, depending on the amount of the liquid lipid incorporated. These results demonstrate how spectroscopic imaging techniques can be valuable in pharmaceutical development, as well as the importance of choosing the type and proportion of solid lipid to achieve stable NLC formulations.

Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmaniasis treatment

Leishmaniasis are a group of neglected infectious diseases caused by protozoa of the genus Leishmania with distinct presentations. The available leishmaniasis treatment options are either expensive and/or; cause adverse effects and some are ineffective for resistant Leishmania strains. Therefore, molecules derived from natural products as the monoterpene carvacrol, have attracted interest as promising anti-leishmania agents. However, the therapeutic use of carvacrol is limited due to its low aqueous solubility, rapid oxidation and volatilization. Thus, the development of nanostructured lipid carriers (NLCs) was proposed in the present study as a promising nanotechnology strategy to overcome these limitations and enable the use of carvacrol in leishmaniasis therapy. Carvacrol NLCs were obtained using a warm microemulsion method, and evaluated regarding the influence of lipid matrix and components concentration on the NLCs formation. NLCs were characterized by DSC and XRD as well. In addition, to the in vitro carvacrol release from NLCs, the in vitro cytotoxicity and leishmanicidal activity assays, and the in vivo pharmacokinetics evaluation of free and encapsulated carvacrol were performed. NLCs containing carvacrol were obtained successfully using a warm microemulsion dilution method. The NLCs formulation with the lowest particle size (98.42 ± 0.80 nm), narrowest size distribution (suitable for intravenous administration), and the highest encapsulation efficiency was produced by using beeswax as solid lipid (HLB=9) and 5% of lipids and surfactant. The in vitro release of carvacrol from NLCs was fitted to the Korsmeyer and Peppas, and Weibull models, demonstrating that the release mechanism is probably the Fickian diffusion type. Moreover, carvacrol encapsulation in NLCs provided a lower cytotoxicity in comparison to free carvacrol (p<0.05), increasing its in vitro leishmanicidal efficacy in the amastigote form. Finally, the in vivo pharmacokinetics of carvacrol after IV bolus administration suggests that this phenolic monoterpene undergoes enterohepatic circulation and therefore presented a long half-life (t1/2) and low clearance (Cl). In addition, C0, mean residence time (MRT) and Vdss of encapsulated carvacrol were higher than free carvacrol (p < 0.05), favoring a higher distribution of carvacrol in the target tissues. Thus, it is possible to conclude that the developed NLCs are a promising delivery system for leishmaniasis treatment.

Development of nanostructured lipid carrier (NLC) assisted with polysorbate nonionic surfactants as a carrier for l-ascorbic acid and Gold Tri.E 30.

Lipid nanocarrier displays the advantages over conventional drug carriers as they are formulated with biodegradable and non-irritant lipids. However, the main drawbacks are the agglomeration of lipid particles, instability over storage, low drug loading, and the burst release of active ingredients. In this study, we investigated the effects of various polysorbate nonionic surfactants namely Tween 20, 40, 60, or 80 on the nanostructured lipid carrier (NLC). NLC incorporated with polysorbate nonionic surfactant was prepared by using high-pressure homogenization technique. The average size was reduced to 139.9 ± 15.8nm in the presence of Tween 80 and remained stable in nano-size even incubated for 28days. Encapsulation of l-ascorbic acid or Gold Tri.E 30 showed a high encapsulation efficiency of more than 75%, where the highest was Gold Tri.E in the presence of Tween 60 at 99.7%. In vitro release study showed that the release of both l-ascorbic acid and Gold Tri.E was significantly reduced in NLC with Tween as compared to bare active ingredients and NLC without Tween. In conclusion, the incorporation of Tween successfully produced a lipid nanocarrier that has the potential to be developed as a carrier of various active ingredients such as nutrients, extracts, and drugs.

Development of nanostructured lipid carriers containing finasteride

Beyond its aesthetic importance, the hair distinguishes the individual and can influence the social acceptance. Under certain circumstances, the normal hair growth process is impaired by a condition called androgenetic alopecia (AGA). Among the drugs used to treat AGA, finasteride is an anti-androgenic steroid, used both orally and topically. Nevertheless, it has been reported that both forms results in side effects such as irritation, contact dermatitis and mood changes. Nanostructured lipid carriers incorporating finasteride were developed in this study, in order to evaluate its main characteristics considering size, zeta potential, polydispersity index, encapsulation efficacy and cytotoxicity. Such nanoparticles were built with lipids from vegetable source and block copolymers. They were adjusted to release the drug using specific temperature as trigger. After preparation through high shear technique, the lipid nanocarriers produced exhibited hydrodynamic diameter with average size of 119.56 ± 1.07 nm and polydispersity index of 0.186. Encapsulation efficiency reached values close to 100% after HPLC quantification. The suspension kept their characteristics through 30 days, showing good stability. In addition, the nanostructures reduced the finasteride cytotoxicity for fibroblasts and keratinocytes cells. In this way, the obtained formulation becomes a good candidate for future in vivo tests as topical agent against AGA showing high encapsulation efficiency and lower cytotoxicity when compared to finasteride alone.

Development of nanostructured lipid carriers containing the antimicrobial ciprofloxacin for topical application

Ciprofloxacin (CIP), a broad spectrum antibacterial agent from the fluoroquinolone family, blocks the activity of the bacterial DNA gyrase. CIP has a limited aqueous solubility and fast clearance rate. Nanostructured lipid carriers (NLC) are drug delivery carriers very appropriate to upload hydrophobic drugs, improving their bioavailability, stability and potency. This work describes the development of NLC containing CIP, their physicochemical characterization and antimicrobial activity, in vitro. NLC particles (215-355 nm) of low size polidispersion (PDI 0.08-0.31) and negative zeta potentials (|20.7-38.7| mV) were prepared; scanning electron microscopy revealed their spherical shapes and regular contour. The particles remained stable during 365 days of storage at 25°C. The encapsulation efficiency of CIP ranged from 72.5 - 95.2%, with a sustained release profile (48 h). Preliminary antimicrobial susceptibility tests revealed a 30% increase in CIP action, when encapsulated in NLC. These proof-of-concept results show the great pharmaceutical and technological potential of the developed nanoformulations. After further tests we believe that NLC-CIP can come to be a novel pharmaceutical form to potentiate the antibiotic effect, reducing its dosage and undesirable side effects.

Crystallization, Polymorphism and Stability of Nanostructured Lipid Carriers Developed with Soybean Oil, Fully Hydrogenated Soybean Oil and Free Phytosterols for Food Applications

The aim of this work was the development of nanostructured lipid carriers (NLC) using conventional fats and oils (soybean oil, SO and fully hydrogenated soybean oil, FHSO) for incorporation of free phytosterols (FP). FP are lipophilic bioactive compounds which can reduce blood cholesterol levels, through a competitive mechanism of absorption, aiding in the prevention of cardiovascular diseases. However, FP presents difficulties related to technological applications in foods due to the high melting point. In this way, NLC can be a means of making feasible incorporation of FP in foods. NLC were obtained in aqueous dispersion through the emulsification process, followed by high-pressure homogenization (HPH) using 3 and 5 cycles at 800 bar, with subsequent crystallization and stabilization of the lipid matrices (LM). The emulsifiers used were soybean lecithin (SL), ethoxylated sorbitan monooleate (T80) and sorbitan monostearate (S60). The thermal and crystalline behavior of the LM, FP and NLC were evaluated. NLCs were characterized by size and polydispersity. FP presented high crystallization (126°C) and melting (137°C) temperatures, but this did not avoid its incorporation into NLC. The NLC presented size between 154 to 534 nm and polydispersity ranging from 0.1 to 0.5, the lower limits being obtained with the T80. NLC were found to require lower temperatures to crystallize and polymorphic transitions were accelerated. This study indicated that the conventional raw materials were compatible with the development of NLC with FP.

The incorporation of Pterodon pubescens fruit oil into optimized nanostructured lipid carriers improves its effectiveness in colorectal cancer

The 23 full factorial design was used to optimize the development of nanostructured lipid carriers (NLCs) containing P. pubescens fruit oil by the melt-emulsification method. The effects of the type of solid lipid, concentration of Phospholipon® 80H and type of aqueous surfactant in parameters such as particle size, polydispersity index (PI), zeta potential (ZP), total content (TC), and encapsulation efficiency (EE) of vouacapans were evaluated. The preparation method of the NLCs was appropriate as the chemical profile of the oil remained unchanged before and after the development process. The studied factors proved to affect the NLCs quality factors at different significant levels. The NLC that presented the best results was the formulation F4, which was produced with Precirol® ATO 5, 0.5% Phospholipon® 80H, and PEG-40 hydrogenated castor oil/sorbitan oleate. The optimized formulation showed small and spherical particles of 94.47 ± 2.05 nm, a PI of 0.197 ± 0.003, ZP less than –30 mV, and excellent physical stability after dispersion analysis. In addition, high values (>98%) of the TC and EE of vouacapans were obtained. X-ray diffraction, Fourier transform Raman spectroscopy and differential scanning calorimetry analysis were also performed. The results suggested that lipids may be partially recrystallized and less ordered in NLCs and that between the P. pubescens oil and lipid matrix an interaction may exist. The P. pubescens fruit oil presented in vitro cytotoxicity to HT-29 cells, with CC50 of 273.47 μg/mL, and was more cytotoxic when incorporated into NLCs (CC50 of 154.19 μg/mL), which justifies the use of such technology in the development of novel phytopharmaceutical products.