Production Of Solid Lipid Nanoparticles Research Articles

Establishment of a semi-continuous nano-production line using the Microfluidizer® technology for the fabrication of lipid-based nanoparticles part 1: Screening of critical parameters and design of experiment optimization studies

A variety of strategies for producing high-quality nanoparticles have been reported in recent years. Batch-based bottom-up and top-down technologies are generally the most efficient methods, but present a number of challenges, particularly in terms of variability, safety, sustainability and large-scale production. In this study, a scalable, semi-continuous production line was built by connecting individual processing units, including a high shear mixing device, the Microfluidizer® technology and a cooling system. Each unit was equipped with an adequate temperature control to allow solvent-free production of solid lipid nanoparticles (consisting of Precirol® ATO 5 or Gelucire® 43/01) and nanostructured lipid carriers (additionally comprising Labrafac™ lipophile WL 1349). Subsequently, critical formulation parameters and critical process parameters (CPPs) of the individual processing units and their effects on particle size (i.e., critical quality attribute (CQA)) were investigated to identify appropriate input parameters for the subsequent Design of Experiment (DoE) studies conducted after linking the process units to a semi-continuous production line. For particle size monitoring, spatially resolved dynamic light scattering (SR-DLS) measurements were conducted and compared to standard DLS measurements to evaluate the applicability of SR-DLS as an inline monitoring tool. It was found that matrix composition, emulsifier concentration, pressure and number of cycles when processing through Microfluidizer® processor were the most influencing parameters. By optimizing these parameters, five-times higher throughputs could be achieved by the semi-continuous manufacturing line. In addition, the particle size measurements with SR-DLS confirmed the feasibility of implementing this technology for real-time particle size monitoring as an important safety factor in quality control.

Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18-Optimization, Characterization, and Cosmetic Application.

Solid lipid nanoparticles (SLNs) incorporated with retinol and oligopeptide can have a full spectrum of effects on the skin as a compatible combination of ingredients with broad anti-aging properties. The research's main objective was to ensure the stability of lipid nanocarriers containing retinol and peptide due to the planned use of this dispersion as a cosmetic raw material. To confirm the effectiveness of method optimization (high shear homogenization, HSH) and proper selection of substrates, SLN dispersions were obtained in three combinations: 1-non-incorporated SLNs; 2-SLNs containing only retinol; 3-SLNs containing retinol and pentapeptide-18; these were then stored at different temperatures (4, 25, 45 °C) for 4 weeks. The desired values of the physicochemical parameters of the optimized dispersion of lipid nanoparticles incorporated with retinol and oligopeptide over the required storage period were confirmed: mean particle size (Z-Ave) = 134.7 ± 0.3 nm; polydispersity index (PDI) = 0.269 ± 0.017 [-]; zeta potential (ZP) = 42.7 ± 1.2 mV (after 4 weeks at 25 °C). The results confirmed the proper selection of the SLN production method and the effectiveness of the optimization performed. The possibility of using the obtained raw material as an ingredient in cosmetic products with anti-aging properties was indicated.

Chondroitin Sulfate for Cartilage Regeneration, Administered Topically Using a Nanostructured Formulation.

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations.

IN VITRO EVALUATION OF THE ANTIBACTERIAL EFFECT OF CHITOSAN COATED TEICOPLANIN-LOADED LIPID NANOPARTICLES AGAINST STAPHYLOCOCCUS AUREUS

Objective: The aim of this research is to formulate teicoplanin-loaded solid lipid nanoparticles (SLN) coated with chitosan to sustain teicoplanin release for effective antibacterial therapy. Material and Method: “Double emulsion-solvent evaporation technique was used for the production of SLNs. The nanoparticles were characterised in terms of morphology, size, encapsulation efficacy, in-vitro drug release and antibacterial activity studies after optimization of process and formulation parameters. Result and Discussion: Transmission electron microscopy images confirmed the formation of spherical SLNs. With chitosan coating, the size increased (from 80 nm to 106 nm) and the negative value of zeta potential (- 11.29) changed to positive (+34.41). The in-vitro release data showed prolonged release of teicoplanin from optimized SLN and chitosan-coated SLN (c-SLN) formulations over 1 week. The antibacterial activity study (S. aureus and Methicillin-resistant S. aureus) showed the activity of the teicoplanin loaded SLN formulations. In conclusion, this study demonstrated the potential of c-SLN for effective delivery of teicoplanin.

Microfluidic encapsulation of enzymes and steroids within solid lipid nanoparticles

The production of solid lipid nanoparticles (SLNs) is challenging, especially when considering the incorporation of biologics. A novel in-house method of microfluidic production of biologic-encapsulated SLNs is proposed, using a variety of base materials for formulation to help overcome the barriers presented during manufacture and administration. Trypsin is used as a model drug for hydrophilic encapsulation whilst testosterone is employed as a positive non-biologic lipophilic control active pharmaceutical ingredient. Particle sizes obtained ranged from 160 to 320 nm, and a lead formulation has been identified from the combinations assayed, allowing for high encapsulation efficiencies (47–90%, respectively) of both the large hydrophilic and the small hydrophobic active pharmaceutical ingredients (APIs). Drug release profiles were analysed in vitro to provide useful insight into sustained kinetics, providing data towards future in vivo studies, which displayed a slow prolonged release for testosterone and a quicker burst release for trypsin. The study represents a large leap forward in the field of SLN production, especially in the field of difficult-to-encapsulate molecules, and the technique also benefits from being more environmentally sustainable due to the use of microfluidics.Graphical

Polymorphic Phase Transitions in Bulk Triglyceride Mixtures

Triacylglycerols (TAGs) are among the most important ingredients in food, cosmetic and pharmaceutical products. Many physical properties of such products, incl. morphology, texture and rheology, are determined by the phase behaviour of the included TAGs. Triglycerides are also of special interest for the production of solid lipid nanoparticles, applied for controlled drug delivery and for encapsulation of bioactive ingredients. In this paper, we study the polymorphic behaviour of complex TAG mixtures, composed of 2 to 6 mixed TAGs, by differential scanning calorimetry and X-ray scattering techniques, aiming to reveal the general rules for their phase behaviour upon cooling and heating. The results show that two or more coexisting phases form upon solidification $(\alpha$, $\beta'$ and/or $\beta)$, the number of which depends strongly on the cooling rate and on the number of components in the mixture. No completely miscible $\alpha$- or $\beta'$-phases were observed. The structure of the most stable $\beta$ polymorphs, formed upon subsequent heating of the solidified samples, does not depend on the thermal history of the samples. For all mixtures studied, we observed one-component $\beta$ domains, coexisting with binary mixed $\beta$ domains with composition and structure which do not depend on the specific TAG ratio in the mixture. In other words, for a mixture with $k$ saturated TAGs we observed $(2k-1)$ different $\beta$ phases. These conclusions provide some predictive power when analysing the phase transition properties of TAG mixtures.

Microfluidic assembly of “Turtle-Like” shaped solid lipid nanoparticles for lysozyme delivery

After two decades of research in the field of nanomedicine, nanoscale delivery systems for biologicals are becoming clinically relevant tools. Microfluidic-based fabrication processes are replacing conventional techniques based on precipitation, emulsion, and homogenization. Here, the focus is on solid lipid nanoparticles (SLNs) for the encapsulation and delivery of lysozyme (LZ) as a model biologic. A thorough analysis was conducted to compare conventional versus microfluidic-based production techniques, using a 3D-printed device. The efficiency of the microfluidic technique in producing LZ-loaded SLNs (LZ SLNs) was demonstrated: LZ SLNs were found to have a lower size (158.05 ± 4.86 nm vs 180.21 ± 7.46 nm) and higher encapsulation efficacy (70.15 ± 1.65 % vs 53.58 ± 1.13 %) as compared to particles obtained with conventional methods. Cryo-EM studies highlighted a peculiar turtle-like structure on the surface of LZ SLNs. In vitro studies demonstrated that LZ SLNs were suitable to achieve a sustained release over time (7 days). Enzymatic activity of LZ entrapped into SLNs was challenged on Micrococcus lysodeikticus cultures, confirming the stability and potency of the biologic. This systematic analysis demonstrates that microfluidic production of SLNs can be efficiently used for encapsulation and delivery of complex biological molecules.

Overview on Solid Lipid Nanoparticle for Topical Delivery and its Inevitable Applications

Solid lipid nanoparticle is a novel approach for topical drug delivery. As lipids used in preparation of solid lipid nanoparticles (SLN) will also get absorbed in skin layers, enhancing permeation across the biological membranes. For the stability of SLN dispersion, several surfactants were used. Mechanism incorporating for the preparation of SLN also impacts particle size and stability. Since the mechanism of SLN through the biological membrane is still under research as it may follow various skin penetration pathways. This review suggests the various method of preparation, common pathways of skin permeation, lipids and surfactant utilized in the production of SLN.

Solid Lipid Nanoparticles (SLNs) with Potential as Cosmetic Hair Formulations Made from Otoba Wax and Ultrahigh Pressure Homogenization

The development and physicochemical characterization of solid lipid nanoparticles (SLNs) with potential for formulating hair cosmetic products were carried out. SLNs were made from Otoba wax, which is native to the tropical Andean region and has a high chemical composition of fatty acids with intermediate chains. SLNs were formulated by preparing wax-in-water dispersions at two internal phase proportions (low = 5% w/w and high = 20% w/w), using the same ratio of surfactant system and preservatives. The coarse dispersions were subjected to ultrahigh pressure homogenization (UHPH), and thermal stability assays for 4 weeks were carried out, where changes in Creaming Index, droplet size, polydispersity, viscosity, zeta potential, conductivity, and pH were evaluated. The results showed that Otoba wax has a required HLB value around 9 and is mainly composed of lauric (~35%) and myristic (~45%), which have been reported to improve the condition of hair loss. Regarding the development on SLNs, it was found that the internal phase concentration did not considerably affect the physicochemical and microbiological properties. Likewise, it was found that UHPH enabled the production of SLNs with particle sizes <200 nm, low polydispersity (<0.3), high zeta potential values, and suitable physical and microbiological stability. Therefore, Otoba wax has potential for the development of SLNs applicable to cosmetic formulations, especially for hair products.

Solid Lipid Nanoparticles (SLN) as a Novel Drug Delivery System: A Theoretical Review

The introduction of solid Lipid Nanoparticles (SLN) for the first time in late 1991 to be a substitute transporter system to what known old colloidal carriers, like emulsions, liposomes, and polymeric micro- and nanoparticles. SLN has merits and potentialities of Classical structures except avoiding some of their common and known disadvantages. This paper reviews SLN production techniques, The integration of drugs, the capacity to load and the release of drugs, with particular emphasis on drug discharge techniques. Issues relating to the introduction of the SLN into the pharmaceutical industry, like the excipients position. From the very beginning a special and wide interest paid to Lipid nanoparticles (LNPs) during the last decade. Nanostructured lipid transporters strong lipid nanoparticles (SLNs) become the most two essential forms of nanoparticles formed from lipids. SLNs were designed to be able to overcome certain restrictions types of colloidal vectors, like liposomes, emulsions, and polymeric nanoparticles as they possess bright sides like strong discharge profile and guided distribution of drugs with the most perfect physical health. NLCs will amend the SLNs in the next generation of lipid nanoparticles in a way that enhances stability, safety and capacity loading. This paper focuses on methods to reduce toxic effects using advanced production techniques such as homogenization and solvent evaporation. As it facilitates way for the solid lipid nanoparticles approval as novel or targeted medication distribution system by using several recent analytical techniques like electron microscopy and dynamic light scattering (DLS), differential scanning calorimetry (DSC), nuclear magnetic resonance, atomic force microscopy and their evaluation parameters concurrent with the application. Conclusion • Solid lipid nanoparticles (SLNs) represent a transport system alternative to conventional colloidal carriers. • SLNs combine the advantages of traditional and modern systems if some of their major difficult proceedings are eliminated. • SLN production techniques include drug incorporation, drug loading and release capacity, with a special focus on drug release methods. • SLNs as novel system and targeted drugs delivery method through using recent techniques.

The use of quantitative analysis and Hansen solubility parameter predictions for the selection of excipients for lipid nanocarriers to be loaded with water soluble and insoluble compounds

The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, viz., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto’s molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT < 4.0 MPa1/2. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.

Lipid Nanoparticle Topical and Transdermal Delivery: A Review on Production, Penetration Mechanism to Skin

Nanoparticulate drug delivery systems have an advanced and modern approach over the traditional delivery system. This systematic review on nanoparticulate drug delivery containing lipid and focus on preparation, challenges and advancement of delivery of the drug via topical and transdermal route. The first era of lipid nanoparticles were SLN and have more sustaining action as well as suitable for the higher permeation of drug. The NLC is the second generation lipid nanoparticles developed to overcome the limitation associated with SLN i.e low drug loading capacity, polymorphism of solid lipid. Production of solid lipid nanoparticles and nanostructured lipid carriers are produced by a variety of technologies which explored in the current review. Lipid nanoparticle has various properties for topical use of cosmetics and other pharmaceutical formulation, i.e. controlled and sustained release of medicaments, Physical and chemical stability of active pharmaceutical ingredients, targeted release, film formation and enhancing penetration with the enhancement of skin hydration. Skin hydration plays a major role in the topical delivery of API as it hydrates the skin which leads to opening of pores of skin. Due to occlusion nature of lipid nanoparticles trans epidermal water loss decline which softening the skin. The use of biodegradable grade lipid makes it more suitable because it does not cause any toxicity as created by polymeric nanoformulations. Furthermore, a discussion about the benefit/risk ratio of a nanoparticulate system containing lipids also explored in this paper. The SLN and NLC are a “nanosafe” carrier for the delivery of active pharmaceutical via topical route.

Praziquantel-Solid Lipid Nanoparticles Produced by Supercritical Carbon Dioxide Extraction: Physicochemical Characterization, Release Profile, and Cytotoxicity.

Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~−28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ.

Soft Cationic Nanoparticles for Drug Delivery: Production and Cytotoxicity of Solid Lipid Nanoparticles (SLNs)

The surface properties of nanoparticles have decisive influence on their interaction with biological barriers (i.e., living cells), being the concentration and type of surfactant factors to have into account. As a result of different molecular structure, charge, and degree of lipophilicity, different surfactants may interact differently with the cell membrane exhibiting different degrees of cytotoxicity. In this work, the cytotoxicity of two cationic solid lipid nanoparticles (SLNs), differing in the cationic lipids used as surfactants CTAB (cetyltrimethylammonium bromide) or DDAB (dimethyldioctadecylammonium bromide), referred as CTAB-SLNs and DDAB-SLNs, respectively, was assessed against five different human cell lines (Caco-2, HepG2, MCF-7, SV-80, and Y-79). Results showed that the cationic lipids used in SLN production highly influenced the cytotoxic profile of the particles, with CTAB-SLNs being highly cytotoxic even at low concentrations (IC50 &lt; 10 µg/mL, expressed as CTAB amount). DDAB-SLNs produced much lower cytotoxicity, even at longer exposure time (IC50 from 284.06 ± 17.01 µg/mL (SV-80) to 869.88 ± 62.45 µg/mL (MCF-7), at 48 h). To the best of our knowledge, this is the first report that compares the cytotoxic profile of CTAB-SLNs and DDAB-SLNs based on the concentration and time of exposure, using different cell lines. In conclusion, the choice of the right surfactant for biological applications influences the biocompatibility of the nanoparticles. Regardless the type of drug delivery system, not only the cytotoxicity of the drug-loaded nanoparticles should be assessed, but also the blank (non-loaded) nanoparticles as their surface properties play a decisive role both in vitro and in vivo.

Influence of glyceryl behenate, tripalmitin and stearic acid on the properties of clarithromycin incorporated solid lipid nanoparticles (SLNs): Formulation, characterization, antibacterial activity and cytotoxicity

Clarithromycin (CLR) is a macrolide derivative which is included in BCS class 2 with low oral bioavailability. Solid lipid nanoparticles (SLNs) have been studied by many researchers for drug application and are very popular systems that continue to be studied. However, the effects of lipids used in SLN production on the formulation properties are one of the few studied topics. Therefore, the aim of this study was to formulate CLR incorporated SLN formulations by ‘high-speed homogenization technique’’ for oral administration and also elucidate the effect of three types of lipid matrix on particle size (PS), polydispersity index (PDI), drug content, release properties etc. For this reason, three types of major lipid matrix (Glyceryl behenate, Tripalmitin and Stearic acid) were chosen in this study. Seven different formulations were characterized in detail and the results were discussed. The PSs of the CLR incorporated SLNs were between 318 and 526 nm. The average PDI of blank nanoparticles varied between 0.211 and 0.409, whereas the average PDI of CLR incorporated SLNs were between 0.228 and 0.472. The drug content was a range of 63–89%. In vitro release studies of SLNs showed extended-release up to 48 h after the first 6 h of burst effect. Both the burst effect kinetics and the 48-h release kinetics were investigated. The results showed that the burst effect was fitted to the Korsmeyer-Peppas model and 48 h to the Baker-Lonsdale model. The structures of the formulations were clarified by DSC & FT-IR analysis. The results showed that PS, PDI, drug content and release rates of SLNs were directly related to the carbon chain length of lipid. Antibacterial activity of the formulations was tested against Staphylococcus aureus by microdilution and agar well diffusion methods. Formulations A3, A5, A6 and A7 rendered CLR, 2 times more effective against its target according to the microdilution method. As for the agar well method, clear zones around A3, A5, A6, and A7 wells were the same size or larger than clarithromycin zone. The cell viability test was performed with MTT in the NIH 3T3 mouse embryonic fibroblast cell line. At the end of the incubation times, no cell viability differences were observed between CLR and formulations. As a result, in vitro characterization and release data demonstrated the possibility of improved bioavailability of CLR by SLN formulation and the effect of lipid used in this study on formulation characteristics were elucidated in detail. At least in terms of some formulations, improved pharmacodynamic effects were also obtained from antibacterial activity studies.

Lipid nanoparticle topical &amp; transdermal delivery: a review on production, penetration mechanism to skin

Lipid nanoparticles are an alternative and modern carrier system to traditional drug delivery system i.e. liposomes and emulsions. This systematic review on lipid nanoparticles focus on production, challenges and advancement of delivery of drug via topical and transdermal route. Production of solid lipid nanoparticles and naostructured lipd carrier are produced by a variety of technique which explored in current review. Lipid nanoparticle exhibit many features for topical application of cosmetics and pharmaceutics, i.e. controlled release of actives, Physical and chemical stability of active pharmaceutical ingredients, drug targeting, occlusion, film formation and associated with it penetration enhancement and increase of skin hydration. Due to the production of lipid nanoparticles from physiological and/or biodegradable lipids, this carrier system exhibits an excellent tolerability. Furthermore an overview of the benefit/risk ratio of lipid nanoparticles also explored in this paper. The SLN &amp; NLC are a “nanosafe” carrier for the delivery of active pharmaceutical via topical route.

Polymorphism, Crystallinity and Hydrophilic-Lipophilic Balance (HLB) of Cetearyl Alcohol and Cetyl Alcohol as Raw Materials for Solid Lipid Nanoparticles (SLN)

The use of Solid Lipid Nanoparticles (SLN) has become a very popular approach in the development of innovative pharmaceutical drug delivery systems. The first step is the assessment the lipids’ suitability. This paper is focused on the physicochemical characterization of lipids, namely cetyl alcohol and cetearyl alcohol, for the production of SLN. The bulk lipids were analyzed by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD) without any treatment, after tempering the raw materials (bulk lipid) for 1 hour at 80 ℃, and after their spray-drying process.

Production of solid lipid nanoparticles with a supercritical fluid assisted process

In this work, a supercritical fluid continuous process, the Supercritical Assisted Injection in a Liquid Antisolvent (SAILA), was proposed for the production of solid lipid nanoparticles (SLNs).SLNs of soy lecithin, cholesterol and stearic acid were produced in this work. Acetone and ethanol were used as solvents. The effect of lipid concentration on particles size distribution and morphology was studied. SLNs with mean dimensions included between 158 ± 53 nm and 326 ± 169 nm were obtained for soy lecithin particles, between 151 ± 74 nm and 207 ± 57 nm for cholesterol and from 364 ± 77 nm to 462 ± 88 nm for stearic acid particles. All the suspensions were stable over 30 days of observation.

A Method for Efficient Loading of Ciprofloxacin Hydrochloride in Cationic Solid Lipid Nanoparticles: Formulation and Microbiological Evaluation.

The aim of the study was the production of solid lipid nanoparticles (SLN) loaded with ciprofloxacin (CIP) through two different production techniques, quasi-emulsion solvent diffusion (QESD) and solvent injection (SI). In order to efficaciously entrap the commercial salt form (hydrochloride) of the antibiotic in these lipid systems, a conversion of CIP hydrochloride to the free base was realized in situ, through the addition of triethylamine. To ensure physical stability to the carriers over time and ameliorate the interaction with bacterial cell membranes, positively charged SLN were produced by addition of the cationic lipid didecyldimethylammonium bromide (DDAB). Homogeneous SLN populations with a mean particle sizes of 250–350 nm were produced by both methods; drug encapsulation was over 85% for most samples. The SLN were physically stable for up to nine months both at 4 °C and 25 °C, although the former condition appears more suitable to guarantee the maintenance of the initial particle size distribution. As expected, CIP encapsulation efficiency underwent a slight reduction after nine months of storage, although the initial high drug content values would ensure a residual concentration of the antibiotic in the SLN still appropriate to exert an acceptable antibacterial activity. Selected SLN formulations were subjected to an in vitro microbiological assay against different bacterial strains, to verify the effect of nanoencapsulation on the cell growth inhibitory activity of CIP. In general, CIP-SLN produced without DDAB showed MIC values for CIP comparable to those of the free drug. Conversely, addition of increasing percentages of the cationic lipid, reflected by a progressive increase of the positive value of the Zeta potential, showed a variety of MIC values against the various bacterial strains, but with values 2–4 order of dilution lower than free CIP. An hypothesis of the effect of the cationic lipid upon the increased antibacterial activity of CIP in the nanocarriers is also formulated.

Mannose-functionalized solid lipid nanoparticles are effective in targeting alveolar macrophages

Mannose receptor is highly expressed on alveolar macrophages, being a potential target to promote the specific local drug delivery of anti-tuberculosis agents through the use of functionalized nanocarriers. In this work, isoniazid (Isn)-loaded solid lipid nanoparticles (SLN), reinforced with stearylamine (SA) were produced by double emulsion technique and further surface-functionalized with mannose in a straightforward chemical approach. Upon pre-formulation assessment, SLN close to 500 nm average size, positively charged and with association efficiency of ISN close to 50% were obtained. Functionalization with mannose was performed after SLN production and confirmed by Fourier transform infrared spectroscopy (FTIR). Both functionalized and non-functionalized SLN demonstrated to devoid of toxicity when tested in human lung epithelial cell line (NCI-H441) and differentiated THP-1 (dTHP-1), reducing the intrinsic cytotoxicity of Isn when incorporated into SLN. Uptake studies were conducted on same macrophage-like cells and the results showed that fluorescent mannosylated SLN (M-SLN) were more efficient in be internalized comparatively to SLN. Moreover, the uptake of M-SLN was reduced when cells were pre-incubated with mannose, demonstrating the receptor-dependence internalization of functionalized SLN. These functionalized nanocarriers may represent a useful platform to target alveolar macrophages for delivering anti-infective drugs.