Solid Lipid Nanoparticles (SLN) and Oil-Loaded SLN Studied by Spectrofluorometry and Raman Spectroscopy

Purpose Recently, colloidal dispersions made of mixtures from solid and liquid lipids have been described to overcome the poor drug loading capacity of solid lipid nanoparticles (SLN). It has been proposed that these nanostructured lipid carriers (NLC) are composed of oily droplets, which are embedded in a solid lipid matrix. High loading capacities and controlled release characteristics have been claimed. It is the objective of the present paper to investigate these new NLC particles in more detail to obtain insights into their structure. Methods Colloidal lipid dispersions were produced by high-pressure homogenization. Particle sizes were estimated by laser diffraction and photon correlation spectroscopy. The hydrophobic fluorescent marker nile red (NR) was used as model drug, and by fluorometric spectroscopy, the molecular environment (polarity) was elucidated because of solvatochromism of NR. The packaging of the lipid nanoparticles was investigated by Raman spectroscopy and by densimetry. The light propagation in lipid nanodispersions was examined by refractometry to obtain further insights into the nanostructural compositions of the carriers. Results Fluorometric spectroscopy clearly demonstrates that NLC nanoparticles offer two nanocompartments of different polarity to accommodate NR. Nevertheless, in both compartments, NR experiences less protection from the outer water phase than in a nanoemulsion. In conventional SLN, lipid crystallization leads to the expulsion of the lipophilic NR from the solid lipid. Measurements performed by densimetry and Raman spectroscopy confirm the idea of intact glyceryl behenate lattices in spite of oil loading. The lipid crystals are not disturbed in their structure as it could be suggested in case of oil incorporation. Refractometric data reveal the idea of light protection because of incorporation of sensitive drug molecules in NLC. Conclusion Neither SLN nor NLC lipid nanoparticles did show any advantage with respect to incorporation rate compared to conventional nanoemulsions. The experimental data let us conclude that NLC lipid nanoparticles are not spherical solid lipid particles with embedded liquid droplets, but they are rather solid platelets with oil present between the solid platelet and the surfactant layer.     

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate

The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.     

Polymorphic behaviour of Compritol888 ATO as bulk lipid and as SLN and NLC

CompritolR888 ATO (glycerol behenate) is widely used as a pharmaceutical excipient in the field of solid dosage forms due to its lubricating properties. It is an amphiphilic material with a high melting point (approximately 70 degrees C) and, therefore, it can also be used to prepare aqueous colloidal dispersions. The aim of this paper is to study the suitability of CompritolR888 ATO for the production of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the entrapment of a lipophilic model drug. This study assesses the crystalline structure of the bulk lipid, as well as the changes that occur in its crystal lattice with the addition of 'impurities', such as oil (alpha-tocopherol) and drug (ketoconazole), using DSC and X-ray diffraction analysis before and after thermal stress. Aqueous SLN and NLC dispersions were produced using an appropriate surfactant/co-surfactant system and their physicochemical stability was assessed by PCS, LD, DSC and by WAXS. It was found that the crystalline lattice of CompritolR888 ATO is composed of very small amounts of the unstable alpha polymorphic form characteristic of triacylglycerols, which disappears after thermal stress of bulk lipid. Mixing oils and drug molecules which are soluble in this lipid decreased its lattice organization and, thus, was revealed to be suitable for production of lipid nanoparticles containing ketoconazole. However, particle growth could not be avoided during shelf life.     

Lipid nanoparticles as carrier for octyl-methoxycinnamate: in vitro percutaneous absorption and photostability studies

The aim of the present study was the evaluation of lipid nanoparticles (solid lipid nanoparticles, SLN, and nanostructured lipid carriers, NLC) as potential carriers for octyl-methoxycinnamate (OMC). The release pattern of OMC from SLN and NLC was evaluated in vitro, determining its percutaneous absorption through excised human skin. Additional in vitro studies were performed in order to evaluate, after UVA radiation treatment, the spectral stability of OMC-loaded lipid nanoparticles. From the obtained results, ultrasonication method yielded both SLN and NLC in the nanometer range with a high active loading and a particle shape close to spherical. Differential scanning calorimetry data pointed out the key role of the inner oil phase of NLC in stabilizing the particle architecture and in increasing the solubility of OMC as compared with SLN. In vitro results showed that OMC, when incorporated in viscosized NLC dispersions (OMC-NLC), exhibited a lower flux with respect to viscosized SLN dispersions (OMC-SLN) and two reference formulations: a microemulsion (OMC-ME) and a hydroalcoholic gel (OMC-GEL). Photostability studies revealed that viscosized NLC dispersions were the most efficient at preserving OMC from ultraviolet-mediated photodegradation.     

Physicochemical Investigations on Solid Lipid Nanoparticles and on Oil-Loaded Solid Lipid Nanoparticles: A Nuclear Magnetic Resonance and Electron Spin Resonance Study

Purpose. Recently, colloidal dispersions made of mixtures from solid and liquid lipids have been described to combine controlled-release characteristics with higher drug-loading capacities than solid lipid nanoparticles (SLNs). It has been proposed that these nanostructured lipid carriers (NLCs) are composed of oily droplets that are embedded in a solid lipid matrix. The present work investigates the structure and performance of NLCs. Methods. Colloidal lipid dispersions were produced by high-pressure homogenization and characterized by laser diffraction, photon correlation spectroscopy, wide-angle x-ray scattering, and differential scanning calorimetry. Proton nuclear magnetic resonance spectroscopy and electron spin resonance experiments were performed to investigate the mobility of the components and the molecular environment of model drugs. Furthermore, a nitroxide reduction assay with ascorbic acid was conducted to explore the accessibility of the lipid model drug from the outer aqueous phase. Results. Proton nuclear magnetic resonance spectra clearly demonstrate that NLC nanoparticles differ from nanoemulsions and from SLNs by forming a liquid compartment that is in strong interaction to the solid lipid. The electron spin resonance model drug was found to be accommodated either on the particle surface with close water contact (SLN) or additionally in the oil (NLC). The oil compartment must be localized on the particle surface, because it can be easily reached by ascorbic acid. Conclusion. Neither SLN nor NLC lipid nanoparticles showed any advantage with respect to incorporation rate or retarded accessibility to the drug compared with conventional nanoemulsions. The experimental data let us conclude that NLCs are not spherical solid lipid particles with embedded liquid droplets, but they are rather solid platelets with oil present between the solid platelet and the surfactant layer.     

Investigation of the factors influencing the incorporation of clotrimazole in SLN and NLC prepared by hot high-pressure homogenization

Clotrimazole, a fungicidal effective for the local treatment of cutaneous and mucosal infections, was incorporated into solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The aim was to increase its dermal bioavailability and to control drug release, thereby potentially reducing its side effects. Prior to the release studies, the carrier was optimized and characterized by using different techniques. Laser diffractometry (LD), photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM) indicated that SLN were spherical in shape with a mean size of approximately 400 nm. Some aggregation phenomena occurred during preparation of SEM samples due to the lipid character of the carriers. No physico-chemical instability of the drug-loaded lipid nanoparticles was detected during 2 years of storage at different temperatures. X-ray and DSC results suggested that during storage time the drug remained molecularly dispersed in the lipid matrix. Drug associated to SLN and NLC in its crystal form could be excluded.     

Characterization of indomethacin-loaded lipid nanoparticles by differential scanning calorimetry

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are interesting nanoparticulate delivery systems produced from solid lipids. Both carrier types are submicron size particles but they can be distinguished by their inner structure. In the present paper, indomethacin (IND)-loaded SLN and NLC were prepared and the organization and distribution of the different ingredients originating each type of nanoparticle system were studied by differential scanning calorimetry (DSC) technique. Furthermore, mean particle size and percentage of drug encapsulation were also determined. From the results obtained, NLC lipid organization guaranteed an increased indomethacin encapsulation in comparison with SLN. DSC static and dynamic measurements performed on SLN and NLC showed that oil nanocompartments incorporated into NLC solid matrix drastically influenced drug distribution inside the nanoparticle system. Controlled release from NLC system could be explained considering both drug partition between oil nanocompartments and solid lipid and a successive partition between solid lipid and water.     

Solid lipid nanoparticles and nanostructured lipid carriers--innovative generations of solid lipid carriers

The first generation of solid lipid carrier systems in nanometer range, Solid Lipid Nanoparticles (SLN), was introduced as an alternative to liposomes. SLN are aqueous colloidal dispersions, the matrix of which comprises of solid biodegradable lipids. SLN are manufactured by techniques like high pressure homogenization, solvent diffusion method etc. They exhibit major advantages such as modulated release, improved bioavailability, protection of chemically labile molecules like retinol, peptides from degradation, cost effective excipients, improved drug incorporation and wide application spectrum. However there are certain limitations associated with SLN, like limited drug loading capacity and drug expulsion during storage, which can be minimized by the next generation of solid lipids, Nanostructured lipid carriers (NLC). NLC are lipid particles with a controlled nanostructure that improves drug loading and firmly incorporates the drug during storage. Owing to their properties and advantages, SLN and NLC may find extensive application in topical drug delivery, oral and parenteral administration of cosmetic and pharmaceutical actives. Cosmeceuticals is emerging as the biggest application target of these carriers. Carrier systems like SLN and NLC were developed with a perspective to meet industrial needs like scale up, qualification and validation, simple technology, low cost etc. This paper reviews present status of SLN and NLC as carrier systems with special emphasis on their application in Cosmeceuticals; it also gives an overview about various manufacturing techniques of SLN and NLC.     

Polymorphic behaviour of Compritol®888 ATO as bulk lipid and as SLN and NLC

Compritol®888 ATO (glycerol behenate) is widely used as a pharmaceutical excipient in the field of solid dosage forms due to its lubricating properties. It is an amphiphilic material with a high melting point (～70°C) and, therefore, it can also be used to prepare aqueous colloidal dispersions. The aim of this paper is to study the suitability of Compritol®888 ATO for the production of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the entrapment of a lipophilic model drug. This study assesses the crystalline structure of the bulk lipid, as well as the changes that occur in its crystal lattice with the addition of ‘impurities’, such as oil (α-tocopherol) and drug (ketoconazole), using DSC and X-ray diffraction analysis before and after thermal stress. Aqueous SLN and NLC dispersions were produced using an appropriate surfactant/co-surfactant system and their physicochemical stability was assessed by PCS, LD, DSC and by WAXS. It was found that the crystalline lattice of Compritol®888 ATO is composed of very small amounts of the unstable α polymorphic form characteristic of triacylglycerols, which disappears after thermal stress of bulk lipid. Mixing oils and drug molecules which are soluble in this lipid decreased its lattice organization and, thus, was revealed to be suitable for production of lipid nanoparticles containing ketoconazole. However, particle growth could not be avoided during shelf life.     

Preparation, characterization and biodistribution of nanostructured lipid carriers for parenteral delivery of bifendate

Nanostructured lipid carrier (NLC)-loaded bifendate (DDB) was prepared by melt-emulsification method to improve drug payloads and liver targeting. The particle size of the prepared formulation analysed by photon correlation spectroscopy (PCS) was 217.4?nm with a narrow polydispersity index (PI) lower than 0.2, meanwhile the loading capacity increased from 4.3% to 15.7% in comparison with DDB-loaded SLN reported in previous study. The zeta potential value was -21.91?mV, and transmission electron microscopy studies revealed NLC of irregularly spherical shape. With respect to lipid polymorphism, a less ordered structure of NLC was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In addition, tissue distribution of DDB-loaded NLC and DDB solution were carried out in Kunming strain mice. In tested organs, the distribution of DDB-loaded NLC to liver was higher than that of free drug. These results support the potential applications of NLC for the delivery of DDB.     

Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers

Background and the purpose of the study

Domperidone (DOM) is a dopamine- receptor (D₂) antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle (SLN) and Nanostructured Lipide Carrier (NLC). The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles (DOM-SLN) and DOM loaded nanostructured lipid carriers (DOM-NLC).

Methods

DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99%) and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index (PDI), zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy (TEM). SLN and NLC formulations were subjected to stability study over a period of 40 days.

Results

The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1) and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84% and 32.23 nm, 0.160, 10.47 mV, 90.49% respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the β prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant (P<0.05) change in particle size, zeta potential, PDI and entrapment efficiency indicating the developed SLN and NLC were fairly stable.

Conclusion

Fairly spherical shaped, stable and controlled release DOM-SLN and DOM-NLC could be prepared by hot homogenization followed by ultrasonication technique.     

Preparation,characterization and biodistribution of nanostructured lipid carriers for parenteral delivery of bifendate

Nanostructured lipid carrier (NLC)-loaded bifendate (DDB) was prepared by melt-emulsification method to improve drug payloads and liver targeting. The particle size of the prepared formulation analysed by photon correlation spectroscopy (PCS) was 217.4?nm with a narrow polydispersity index (PI) lower than 0.2, meanwhile the loading capacity increased from 4.3% to 15.7% in comparison with DDB-loaded SLN reported in previous study. The zeta potential value was ?21.91?mV, and transmission electron microscopy studies revealed NLC of irregularly spherical shape. With respect to lipid polymorphism, a less ordered structure of NLC was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In addition, tissue distribution of DDB-loaded NLC and DDB solution were carried out in Kunming strain mice. In tested organs, the distribution of DDB-loaded NLC to liver was higher than that of free drug. These results support the potential applications of NLC for the delivery of DDB.     

Skin moisturizing effect and skin penetration of ascorbyl palmitate entrapped in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) incorporated into hydrogel

This study was performed as a complimentary to our previous study regarding the chemical stability of ascorbyl palmitate (AP) in solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, in nanoemulsion (NE) incorporated into a hydrogel produced by high pressure homogenization. AP is known as an effective antioxidant that protects tissue integrity similar to vitamin C. Recently, its moisturizing activity in conventional topical formulations was found to be high. The aim of the present study was to investigate the moisturizing potential of AP in SLN and NLC incorporated into hydrogel as colloidal carrier systems. It has been known that SLN and NLC have occlusive effects, but AP incorporation moisturized skin significantly better than placebo in short-term (p < 0.001) and long-term trials (p < 0.01) for both SLN and NLC. In the second part of the study, SLN and NLC were found to sustain the penetration of AP through excised human skin about 1/2 and 2/3 times compared to NE (p < 0.001 and p < 0.01), respectively, due to the solid state of Witepsol E85 in the lipid phase.     

Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance

Topical application of lutein as an innovative antioxidant, anti-stress and blue light filter, which is able to protect skin from photo damage, has got a special cosmetic and pharmaceutical interest in the last decade. Lutein is poorly soluble, and was therefore incorporated into nanocarriers for dermal delivery: solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and a nanoemulsion (NE). Nanocarriers were produced by high pressure homogenization. The mean particle size was in the range of about 150 nm to maximum 350 nm, it decreased with increasing oil content of the carriers. The zeta potential in water was in the range -40 to -63 mV, being in agreement with the good short term stability at room temperature monitored for one month. In vitro release was studied using a membrane free model. Highest release in 24h was observed for the nanoemulsion (19.5%), lowest release (0.4%) for the SLN. Release profiles were biphasic (lipid nanoparticles) or triphasic (NE). In vitro penetration study with a cellulose membrane showed in agreement highest values for the NE (60% in 24h), distinctly lower values for the solid nanocarriers SLN and NLC (8-19%), lowest values for lutein powder (5%). Permeation studies with fresh pig ear skin showed that no (SLN, NLC) or very little lutein (0.4% after 24h) permeated, that means the active remains in the skin and is not systemically absorbed. The nanocarriers were able to protect lutein against UV degradation. In SLN, only 0.06% degradation was observed after irradiation with 10 MED (Minimal Erythema Dose), in NLC 6-8%, compared to 14% in the NE, and to 50% as lutein powder suspended in corn oil. Based on size, stability and release/permeation data, and considering the chemical protection of the lutein prior to its absorption into the skin, the lipid nanoparticles are potential dermal nanocarriers for lutein.     

Enhanced payload and photo-protection for pesticides using nanostructured lipid carriers with corn oil as liquid lipid

With the aim to establish a novel nanocarrier system with higher payload and higher photo-protection for deltamethrin (active ingredient) compared to solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) were prepared by combining hot homogenization and sonication with different ratios of corn oil (liquid lipid) and beeswax (solid lipid). Compared to SLN, the incorporation of corn oil gave a higher payload, slower release rate and higher photo-protection for deltamethrin. Particularly, compared to beeswax solid lipid nanoparticles (BSLN), NLC gave a higher payload (approximately 1.79 times) with a high encapsulation efficiency (83.6%), higher photo-protection in direct photolysis (1.8 times) after 12?h exposure of ultraviolet light (UV) and in indirect photolysis (1.37 times) after 2?h exposure of UV in 2% (v/v) acetone solution used as a photosensitizer. This study demonstrated that novel nanocarrier possesses a wide range of applicability in protecting photo-labile compounds for the crop, food and pharmaceutical industries.     

Skin permeation of buprenorphine and its ester prodrugs from lipid nanoparticles: lipid emulsion,nanostructured lipid carriers and solid lipid nanoparticles

The aim of this study was to develop and characterize lipid nanoparticle systems for the transdermal delivery of buprenorphine and its prodrugs. A panel of three buprenorphine prodrugs with ester chains of various lengths was synthesized and characterized by solubility, capacity factor (log K′), partitioning between lipids and water and the ability to penetrate nude mouse skin. Colloidal systems made of squalene (lipid emulsion, LE), squalene + Precirol (nanostructured lipid carriers, NLC) and Precirol (solid lipid nanoparticles, SLN) as the lipid core material were prepared. Differential scanning calorimetry showed that the SLN had a more-ordered crystalline lattice in the inner matrix compared to the NLC. The particle size ranged from 220–300 nm, with NLC showing the smallest size. All prodrugs were highly lipophilic and chemically stable, but enzymatically unstable in skin homogenate and plasma. The in vitro permeation results exhibited a lower skin delivery of drug/prodrug with an increase in the alkyl chain length. SLN produced the highest drug/prodrug permeation, followed by the NLC and LE. A small inter-subject variation was also observed with SLN carriers. SLN with soybean phosphatidylcholine (SLN-PC) as the lipophilic emulsifier showed a higher drug/prodrug delivery across the skin compared to SLN with Myverol, a palmitinic acid monoglyceride. The in vitro permeation of the prodrugs occurred in a sustained manner for SLN-PC. The skin permeation of buprenorphine could be adjusted within a wide range by combining a prodrug strategy and lipid nanoparticles.     

喷雾干燥法固化黄豆苷元固体脂质纳米粒的研究

目的：建立一种干燥的固体脂质纳米粒的制备方法。方法：采用超声分散法制备黄豆苷元固体脂质纳米粒的混悬液,然后采用喷雾干燥法将其制成干燥的、可再分散的固体脂质纳米粒。结果：在混悬液中黄豆苷元固体脂质纳米粒为球形粒子,平均粒径约为280 nm,喷雾干燥后得到的纳米粒仍为球型,分散后的粒径与喷干前相比有所增大,平均粒径约为720 nm,稳定性较好。结论：喷雾干燥法制备黄豆苷元固体脂质纳米粒是可行的。     

Solid lipid nanoparticles (SLNTM/LipopearlsTM) a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products

Solid lipid nanoparticles (SLNTM, LipopearlsTM) are nanoparticles made from solid lipids by highpressurehomogenization. Incorporation of chemically labile active ingredients intothe solid lipid matrix protects against chemical degradation, which is shown for vitamin E. The SLN are physically stable in aqueous dispersions and also after incorporation into a dermal cream as proven by photon correlation spectroscopy and differential scanning calorimetry. Electron microscopy and atomic force microscopy data reveal the spherical shape of the SLN and the detailed structure of the particle surface. Ultrafine particles form an adhesive film leading to an occlusive effect on the skin. The occlusion promotes the penetration of vitamin E into the skin, as shown by the stripping test. In addition to chemical stabilization of active ingredients, occlusive effects on the skin and subsequent enhanced penetration of compounds, the SLN also possess a pigment effect covering undesired colours leading to an increased aesthetic acceptance by the customer.     

Rheology of nanostructured lipid carriers (NLC) suspended in a viscoelastic medium

Colloidal lipid nanoparticle dispersions have been characterized by rheological measurements using two different nanostructured lipid carrier (NLC)-based formulations intended for cosmetic application of substances like sunflower oil and alpha-tocopherol. This study has shown that rheological and viscoelastic properties of aqueous NLC dispersions are quantitatively very different depending on the composition of the oil phase and the temperature of storage despite similar or even identical particle size. NLC were loaded with 30% active ingredient relative to the particle mass. Stearyl alcohol was used as lipid matrix and the particle sizes determined by photon correlation spectroscopy were in the range 210-270 nm. In general, sun flower oil-loaded NLC dispersions showed distinctly higher storage modulus (G'), loss modulus (G") and complex viscosity (eta*). Storage at lower temperature (4 degrees C versus 20 degrees C) delay the build up of a microstructure affected not only by size and stabilizer but also loaded ingredient and storage history after preparation, i.e. storage at room temperature accelerates the build up of a final suspension structure.     

Hydrophilic coating of mitotane-loaded lipid nanoparticles: Preliminary studies for mucosal adhesion

The aim of the present work was to load mitotane, an effective drug for adrenocortical carcinoma treatment, in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The SLN and NLC were successfully prepared by high shear homogenization followed by hot high pressure homogenization. Formulations were composed of cetyl palmitate as the solid lipid for SLN, whereas for NLC PEGylated stearic acid was selected as solid lipid and medium chain triacylglycerols as the liquid lipid. Tween® 80 and Span® 85 were used as surfactants for all formulations. The particle size, zeta potential, polydispersity index (PI), encapsulation efficiency (EE), and loading capacity (LC) were evaluated. The SLN showed a mean particle size of 150?nm, PI of 0.20, and surface charge ?10 mV, and the EE and LC could reach up to 92.26% and 0.92%, respectively. The NLC were obtained with a mean particle size of 250?nm, PI of 0.30, zeta potential ?15 mV and 84.50% EE, and 0.84% LC, respectively. Hydrophilic coating of SLN with chitosan or benzalkonium chloride was effective in changing zeta potential from negative to positive values. The results suggest that mitotane was efficiently loaded in SLN and in NLC, being potential delivery systems for improving mitotane LC and controlled drug release.