Hot High Pressure Homogenization Method Research Articles

Combination of Indomethacin with Nanostructured Lipid Carriers for Effective Anticancer Therapy.

The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin. IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro. Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (-30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 μM. We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.

Design, optimization and in-vivo characterization of mupirocin loaded nanostructured lipid carrier based gel for effective treatment of impetigo

Mupirocin is a broad-spectrum antibiotic effective in treatment of skin infection (Impetigo), but the poor bioavailability limits its use as a conventional dosage form such as tablets, ointment and cream. The present investigation was aimed to design, optimize and evaluate Mupirocin (MC) loaded nanostructured lipid carriers (NLCs) based gel for topical application. Excipients identified were screened for apposite material required for the formulation of NLCs using process variables as the determining factors. The preparation of nanostructured lipid carriers (NLCs) was optimized using 32 factorial design with two independent variables (solid: liquid lipid ratio and surfactant (%)) and two responses (particle size (nm), entrapment efficiency (%)) using hot high pressure homogenization method. The formulation was further characterized for zeta potential (mV), polydispersity index and morphology. The optimized NLC dispersion of Mupirocin (MC) was lyophilized and loaded in 0.75% w/v Carbopol 980 gel and was evaluated for pH, viscosity and drug content. Mupirocin (MC) loaded NLC based gel were characterized for ex-vivo drug permeation and compared with marketed (cream) preparation. Further, drug deposition, skin irritation and stability study was carried out as per ICH guidelines. The optimized formulation (F5) containing Glyceryl behenate: Oleic acid (70:30), and Poloxamer 188 (0.5%) demonstrated smaller particle size (150.02 ± 1.52 nm) with higher drug entrapment efficiency (88.02 ± 1.21%). Mupirocin (MC) loaded NLC based gel demonstrated sustained drug profile with significant increase (P < 0.05) in drug deposition in skin (about 26%) with non-irritant properties to the skin. Stability study showed no significant changes of the parameters during and after the study. In conclusion, developed Mupirocin (MC) loaded NLC based gel could serve as a novel approach in treatment of impetigo by deliver the drug topically with sustained effect and improved patient compliance.

Erythromycin encapsulation in nanoemulsion-based delivery systems for treatment of Helicobacter pylori infection: Protection and synergy

Poorly water-soluble and unstable compounds are difficult to develop as drug products using conventional formulation techniques. The aim of the present study was to develop and evaluate a nanoformulation prepared by a hot high-pressure homogenization method, which was a scalable and solvent-free process. We successfully prepared stable nanodispersions to protect a labile antibiotic, erythromycin. The mean diameter of the dispersed droplets was approximately 150 nm, and size distribution was unimodal. Dispersion was physically stable at room temperature for over six months. Using erythromycin as a model compound, we studied its antimicrobial activity in vitro on Helicobacter pylori. Results showed that drug encapsulation improves API stability in an acidic environment and is conducive to a synergistic effect between the drug and the formulation.

Natural lipids in nanostructured lipid carriers and its cytotoxicity

Nanostructured lipid carriers (NLCs) are active carrier systems which modulate the sustained release of actives and protect unstable compounds against degradation. NLCs can also protect skin from sun light, due to its particulates nature, which gives them intrinsic scattering properties. In this work, we present the preparation of NLCs using natural lipids and its cytotoxicity profile. It was used a vegetal butter with melting point (m.p.) ~32-40°C, an animal wax (m.p. 35-40°C) and a vegetal oil (boiling point ~120-150°C). NLCs were prepared by hot high pressure homogenization method and particles were characterized by average size (Zave), polydispersity index (PDI) and zeta potential (PZ) (Fig.1). The thermal behavior of the NLCs was studied using Differential Scanning Calorimetry (DSC). All the formulations were followed up for 60 days in order to evaluate their stability. NLCs exhibited a Zave around 150-200 nm, PDI less than 0.2 and PZ varying from −25 to −40 mV. The m.p. for the lyophilized NLCs was about 40-56°C. Cytotoxicity of the formulations were evaluated for human keratinocytes (HaCaT) and melanocytes (Melan-A) in the exponential growth phase. Cell viability was used as indicator of cytotoxicity and determined after 4 days of culture by MTT assay. It was found that the NLC formulations were not toxic against HaCaT and Melan-A cells. Results showed that the NLCs produced are potential carriers for nanocosmetics and sunscreen products.

High payload itraconazole-incorporated lipid nanoparticles with modulated release property for oral and parenteral administration.

The aim of this study was to develop high payload itraconazole-incorporated lipid nanoparticles (HINP) with modulated release property using a binary mixture core of solid and liquid lipid for oral and parenteral administration. High payload itraconazole-incorporated lipid nanoparticles were prepared by hot high-pressure homogenization method using tristearin (TS) as a solid lipid, triolein (TO) as a liquid lipid and egg phosphatidylcholine/Tween 80/DSPE-PEG2000 as a surfactants mixture. To investigate the effects of liquid lipid in lipid core on itraconazole (ITZ) dissolution and release, TS/TO ratio was varied as 100/0, 90/10 and 80/20 (mg/mg). All HINP formulations showed particle size around 300 nm and polydispersity index below 0.3. The incorporation efficiencies of HINP formulations were above 80%, and more than 40 mg of ITZ was incorporated into each HINP formulation. In-vitro dissolution and release rate of ITZ from HINP increased as the amount of TO in lipid core increased. Compared with commercial formulations of ITZ, the pharmacokinetics of ITZ was improved after oral and parenteral administration of HINP formulations containing 0% or 10% of TO in lipid core. High payload itraconazole-incorporated lipid nanoparticles with a binary mixture lipid core have a great potential for the development of controlled release formulation of ITZ.

Enhanced acute anti-inflammatory effects of CORM-2-loaded nanoparticles via sustained carbon monoxide delivery

The aim of this study was to enhance the anti-inflammatory effects of carbon monoxide (CO) via sustained release of CO from carbon monoxide-releasing molecule-2-loaded lipid nanoparticles (CORM-2-NPs). CORM-2-NPs were prepared by hot high pressure homogenization method using trilaurin as a solid lipid core and Tween 20/Span 20/Myrj S40 as surfactant mixture. The physicochemical properties of CORM-2-NPs were characterized and CO release from CORM-2-NPs was assessed by myoglobin assay. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. In vivo anti-inflammatory activity was investigated by measuring paw volumes and histological examination in carrageenan-induced rat paw edema. Spherical CORM-2-NPs were around 100nm with narrow particle size distribution. The sustained CO release from CORM-2-NPs was observed and the half-life of CO release increased up to 10 times compared with CORM-2 solution. CORM-2-NPs showed enhanced in vitro anti-inflammatory effects by inhibition of nitric oxide production. Edema volume in rat paw was significantly reduced after treatment with CORM-2-NPs. Taken together, CORM-2-NPs have a great potential for CO therapeutics against inflammation via sustained release of CO.

Heptapeptide-loaded solid lipid nanoparticles for cosmetic anti-aging applications

The cosmetic industry requires more and more expensive actives and ingredients such as retinol, coenzyme Q10, proteins, peptides and biotechnologically produced molecules. In this study, we demonstrate the development of a cost effective formulation of a nanostructured lipid carrier (NLC) or solid lipid nanoparticles (SLN) improving peptide delivery into skin. NLC or SLN are very suitable vehicles for the delivery of active ingredients into skin. The SLN, produced by using hot high pressure homogenization method combine advantages such as physical stability, protection of incorporated labile actives and controlled release. By the used method we dispersed the amorphous heptapeptide DEETGEF in shea butter and homogenized this pre-dispersion at 60°C together with the water phase using a Microfluidizer at 1000bar. The analysis of the obtained SLN-P7 showed a particle size of 173nm, incorporated peptide of 0.014%, entrapment efficiency of 90.8%, melting peak (DSC) of the core lipid of 27°C and a zeta potential of −54mV. By an ex vivo study with skin explants we could stimulate NQO1 (NAD(P)H quinone oxidoreductase), HMOX1 (Heme oxygenase-1) and PRDX1 (Peroxiredoxin-1) genes all of which are cell protecting enzymes. In a multicellular protection against UV induced stress study with skin explants we detected the formation of sun burn cells and the number and morphology of Langerhans cells. The application of our SLN-P7 formulation on skin explants led to a significant and dose dependent protection against UV irradiation. In the clinical suction blister study, irradiation with UVA light for two hours after final product application led to a statistically significant increase of the 8-OhdG (8-hydroxy-2′-deoxyguanosine) concentration in the human epidermis. The skin treated with our verum formulation showed a statistically significant 20% decrease in DNA damage compared to placebo. In conclusion, it was demonstrated that SLN technology enabled peptide delivery into skin allowing it to perform protective functions.

Preparation and Characterization of Minoxidil Loaded Nanostructured Lipid Carriers.

Nanostructured lipid carriers (NLCs) are interesting delivery systems for enhancing the penetration of an active substance through the skin after topical administration. The present paper described the development of a novel NLCs for minoxidil (MXD) topical delivery. Stearic acid and oleic acid that showed the highest solubility for MXD were selected as solid lipid and liquid lipid, respectively, and the NLCs were prepared by hot high pressure homogenization method. The minoxidil loaded NLCs prepared accordingly to the optimal formulation exhibited spherical shape with a mean diameter of 281.4 ± 7.4nm, polydispersity of 0.207 ± 0.009, zeta potential of -32.90 ± 1.23mV, drug entrapment efficiency of 92.48 ± 0.31%, and drug loading of 13.85 ± 0.47%. Storage stability studies demonstrated that the particle size and entrapment efficiency of the MXD-NLCs were not changed during 3months both at 4°C and room temperature. Moreover, the release of MXD from the NLCs was faster than drug release from SLNs. In vitro skin permeability test demonstrated that MXD-NLCs had a more pronounced permeation and retention profile than MXD-SLNs. Furthermore, no erythema was observed after administration of MXD-NLCs. All these results indicated that the developed MXD-NLCs could be a promising and effective nanocarrier for topical delivery of MXD.

Formulation and Evaluation of Solid Lipid Nanoparticle Based Transdermal Drug Delivery System for Alzheimer's Disease

Solid lipid nanoparticles (SLN) loaded formulation as an alternative to oral and parenteral delivery of rivastigmine tartarate (RT), a water-soluble drug by using Precirol ATO 5 and tween 80. The SLN prepared by hot high pressure homogenization method. RT-loaded SLN were stable up to one month of storage. The SLN was found to be zeta potential value of-10 mV, polydispersity index was found in the range 0.3–0.6 with average particle size distribution of 214 nm. The encapsulation efficiency (EE %) was found to be 59.23%. The folding endurance, thickness, drug content uniformity of RT-loaded transdermal patch was found to be 160±1.05 folds, 0.26±0.05mm, 98.63±0.16% respectively. The percent moisture content, percent moisture loss, percent elongation break test was found to be 4.2±0.26%, 3.9±0.31%, 9.23±0.93% respectively. The ex vivo skin permeation and in vitro drug release kinetics has shown 96.90±0.69% permeation and 95.70±0.87% drug release respectively. The RT-SLN loaded transdermal patch was prepared using Eudragit RS100 and Eudragit RL100 and PEG 400 as plasticizer. Formulation was optimized by using full 32 factorial design expert 10. Ex vivo study showed maximum drug release with 24 hours.

Improvement of oral bioavailability of lovastatin by using nanostructured lipid carriers.

Nanostructured lipid carriers (NLCs) have been one of the systems of choice for improving the oral bioavailability of drugs with poor water solubility. In the present study, lovastatin (LVT)-loaded NLCs (LVT-NLCs) were successfully prepared by hot high-pressure homogenization method with high entrapment efficiency, drug loading, and satisfactory particle size distribution. The particles had almost spherical and uniform shapes and were well dispersed with a particle size of <50 nm (23.5±1.6 nm) and a low polydispersity index (0.17±0.05 mV). The result of stability showed that the LVT-NLCs dispersion maintained excellent stability without exhibiting any aggregation, precipitation, or phase separation at 4°C for 6 months of storage. The LVT release data from all developed solid lipid nanoparticles (SLNs) and NLCs were best fitted to a Ritger–Peppas kinetic model (0.9832 and 0.9783 for NLCs and SLNs, respectively). This indicated that the release of LVT from the SLNs and NLCs was due to a combination of drug diffusion and erosion from the lipid matrix. The pharmacokinetic and pharmacodynamic results show that LVT-NLCs were better compared to free drug, which could be attributed to an increase in bioavailability.

Preparation and Characterization of Nanostructured Lipid Carriers Loaded &lt;i&gt;Spirogyra s&lt;/i&gt;pp. Extract

Many compounds with high lipophilic character incorporated into nanostructured lipid carriers (NLC) have been reported. However, hydrophilic compounds have not been completely investigated. In this paper, we investigated the potential of lipid nanoparticles as carriers for aqueous extract of Spirogyra spp. using hot high-pressure homogenization method. The aqueous extract of Spirogyra spp. (AS-NLC) showed spherical morphology with smooth surface under transmission electron microscope (TEM). The encapsulation efficiency was 61.23±6.25%. The crystallization of AS in NLC was investigated by X-ray diffraction. AS was in an amorphous state in the NLC matrix. The in vitro release experiments of NLC exhibited biphasic release pattern with burst release at the initial 3 h and prolonged release afterwards.

Lipid based nanocarriers with different lipid compositions for topical delivery of resveratrol: comparative analysis of characteristics and performance

Nanoemulsion (NE), solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) were produced using hot high-pressure homoge nization method (HPH) and characterized by photon correlation spectroscopy (PCS), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The mean particle sizes of all prepared nanocarriers were in the range of100-150 nm and influenced by the lipid composition. The obtained results of DSC and XRD studies confirmed that the incorporation of liquid lipid into the nanoparticles resulted in the formation of less ordered crystalline lattice. The release rate at the burst release stage could be accelerated by decreasing the liquid lipid ratio. The retention amounts of resveratrol in the skin also depended on the lipid composition. The results showed the potential of lipid based nanocarriers, particularly those with high soild lipid ratio, for topical delivery of resveratrol.

Development of a nanostructured lipid carrier formulation for increasing photo-stability and water solubility of Phenylethyl Resorcinol

The Phenylethyl Resorcinol loaded nanostructured lipid carrier (PR-NLC) was developed by hot high-pressure homogenization method. The freshly prepared PR-NLC showed a spherical morphology under transmission electron microscope, and the particle size was 218.3±9.2nm. The value of the zeta potential of PR-NLC decreased from −30.2±1.9mV to −64.9±1.3mV when the dilution times reach 10. The loading amount of PR encapsulated in NLC was 2.94±0.03%, and the average entrapment efficiencies of PR-NLC determinated by size exclusion chromatography and ultrafiltration were 90.2±0.6% and 98.3±0.3%. Lyophilization was proved feasible for the storage of NLC dispersion. Fourier transform infrared spectra (FTIR) was exploited to investigate the possible drug–lipid complex formation. Advancements in water solubility of PR were demonstrated by NLC using a contact angle measurement. The hemolysis percentage of the NLC was less than 1.3% in a certain range of concentration. In 90 days’ storage, 88.6±2.8% of PR remained unchanged in PR-NLC under natural daylight. In vitro release studies revealed a sustained drug release, and in vitro penetration studies showed an increase of retention amount of PR in the skin, when applying PR-NLC. Therefore, the NLC might be a potential delivery vehicle in cosmetic dermal products.

The efficacy of isotretinoin-loaded solid lipid nanoparticles in comparison to Isotrex® on acne treatment

Topical retinoids are considered as the first line therapy in the treatment of acne vulgaris, but they are associated with cutaneous irritation. In this study, isotretinoin-loaded solid lipid nanoparticles(IT-SLN) were prepared to treat the mild to moderate acne. Also using IT-SLN would minimize IT adverse effects in comparison to commercial product, Isotrex®. This study was conducted to prepare and characterize IT-SLN and assessing the efficiency of IT-SLN comparing to Isotrex® acne. IT-SLN was prepared using hot high pressure homogenization method. IT-SLN contained 0.05% IT in 5% of lipid phase (Glyceryl monostearate- GMS) and tween 80 (2.5 % w/v) was used as surfactant in the aqueous phase. IT-SLN was characterized by particle size analyzing, differential scanning calorimetry and transmission electron microscopy. Encapsulation efficacy was also obtained using spectrophotometry. The efficacy of IT-SLN was evaluated in a randomized, single-blind, parallel-group study and compared with Isotrex®. Forty patients encountered in the study and divided in two groups. Treatment regimen was once-nightly topical administration accompanied with topical administration of clindamycin 2% solution twice a day for 8 weeks. The particle size of IT-SLN was around 60 nm with PDI of 0.4 and zeta potential was about -40 mV. Encapsulation efficacy of IT in SLN in crystalline form was 84±0.21%. IT-SLN produced significantly better treatment than Isotrex® in both non-inflammatory and inflammatory lesions according to its recovery percent after 8 weeks. Also IT-SLN gained better global assessment scores. Our results showed that IT-SLN had higher efficacy than Isotrex® to clear non-inflammatory and inflammatory lesions.

Improved photostability, reduced skin permeation and irritation of isotretinoin by solid lipid nanoparticles / Povećana fotostabilnost, smanjena permeacija i iritacija izotretinoina iz kruto-tekućih nanočestica

The aim of this study was to develop new solid lipid nanoparticles of isotretinoin (IT-SLNs) and evaluate the ability of IT-SLNs to improve photostability, reduce skin permeation and irritating effects. IT-SLNs were prepared by the hot high pressure homogenization method. Size, zeta potential and morphological characteristics of the preparations were assessed by transmission electron microscopy (TEM) and thermotropic properties with differential scanning calorimetry (DSC). IT-SLNs had a small average diameter of 74.05 ± 8.91 nm and high encapsulation efficiency (EE) of 80.6 ± 1.2 %. The results showed that the entrapment of IT into SLNs reduced significantly its photodegradation. The in vitro permeation data showed that IT-SLNs can accumulate in the different layers of the skin and prevent systemic uptake of IT in mouse skin. IT-SLNs also significantly increased IT accumulation in the different layers of the stratum corneum of human skin. IT-SLN formulation was significantly less irritating compared to commercial IT-GEL, which shows its potential for improving skin tolerability and being a carrier for topical delivery of IT.

Topical formulation of retinyl retinoate employing nanostructured lipid carriers

Topical formulation of retinyl retinoate (RR) was developed with nanostructured lipid carriers (NLCs), composed of Compritol or Precirol as a solid lipid, canola oil as an oil, and Tween 80 as a surfactant. Hot high pressure homogenization method was efficiently employed to yield a homogenous nanodispersion in the size range of 230–300 nm with PDI values of <0.2, regardless of lipid selection. Precirol-based NLC (P-NLC) showed higher drug entrapment than that of Compritol-based NLC (C-NLC): RR encapsulation efficiency (%) of P- and C-NLC was 97.8 and 93.8 in average, respectively; drug loading (mg RR/g lipid) was 89.6 and 83.3 in average, respectively. Processing condition at relatively low temperature of 60 °C was a key factor for maintaining RR stability. Drug release of P-NLC was greater than that of C-NLC, even though both NLCs revealed controlled release pattern. Therefore, P-NLC system was considered as a suitable vehicle for topical drug delivery, especially for heat-labile ingredient like RR.

Nanostructured Polymer and Lipid Carriers for Sunscreen. Biological Effects and Skin Permeation

The interest in developing new sunscreens is increasing due to the harmful effects of UV radiation on the skin, such as erythema, accelerated skin ageing (photoageing) and the induction of skin cancer. However, many molecular sunscreens penetrate into the skin causing photoallergies, phototoxic reactions and skin irritation. Thus, the aim of this work was the preparation and characterization of polymeric and solid lipid nanoparticles to act carriers of benzophenone-3 (BZ3), aiming to improve the safety of sunscreen products by increasing the sun protection factor (SPF), decreasing BZ3 skin penetration and decreasing BZ3 concentration in sunscreen formulation. BZ3 was encapsulated in poly(epsilon-caprolactone) (PCL) nanoparticles by the nanoprecipitation method and in solid lipid nanoparticles (SLN) by the hot high pressure homogenization method. The particles were stable for 40 days. The BZ3 encapsulated in PCL nanoparticles was released faster than BZ3 encapsulated in SLN. The sun protection factor increased when BZ3 was encapsulated in both nanostructures. However, BZ3 encapsulated in PCL nanoparticles decreased its skin permeation more than SLN-BZ3. Furthermore, BZ3 encapsulated in SLN did not exhibit cytotoxic or phototoxic effects in human keratinocytes (HaCaT cells) and BABL/c 3T3 fibroblasts, whereas PCL nanoparticles with BZ3 showed phototoxic potential in HaCaT cells. Nevertheless, BZ3 free and encapsulated in PCL nanoparticles or in SLN did not show allergic reactions in mice. Our results suggest that these nanostructures are interesting carriers for sunscreen.

Optimizing flurbiprofen-loaded NLC by central composite factorial design for oculardelivery

The purpose of this study was to design and optimize a new topical deliverysystem for ocular administration of flurbiprofen (FB), based on lipidnanoparticles. These particles, called nanostructured lipid carriers (NLC), werecomposed of a fatty acid (stearic acid (SA)) as the solid lipid and a mixture ofMiglyol® 812 and castor oil (CO) as the liquid lipids, prepared by the hot high pressurehomogenization method. After selecting the critical variables influencing thephysicochemical characteristics of the NLC (the liquid lipid (i.e. oil) concentration withrespect to the total lipid (cOil/L (wt%)), the surfactant and the flurbiprofenconcentration, on particle size, polydispersity index and encapsulation efficiency), athree-factor five-level central rotatable composite design was employed to plan andperform the experiments. Morphological examination, crystallinity and stabilitystudies were also performed to accomplish the optimization study. The resultsshowed that increasing cOil/L (wt%) was followed by an enhanced tendency toproduce smaller particles, but the liquid to solid lipid proportion should not exceed30 wt% due to destabilization problems. Therefore, a 70:30 ratio of SA to oil (miglyol + CO) was selected to develop an optimal NLC formulation. The smaller particlesobtained when increasing surfactant concentration led to the selection of 3.2 wt% ofTween® 80 (non-ionic surfactant). The positive effect of the increase in FB concentrationon the encapsulation efficiency (EE) and its total solubilization in the lipidmatrix led to the selection of 0.25 wt% of FB in the formulation. The optimalNLC showed an appropriate average size for ophthalmic administration(228.3 nm) with a narrow size distribution (0.156), negatively charged surface (−33.3 mV) andhigh EE (∼90%). The in vitro experiments proved that sustained release FB was achieved using NLC asdrug carriers. Optimal NLC formulation did not show toxicity on ocular tissues.

Production and characterization of testosterone undecanoate-loaded NLC for oral bioavailability enhancement

Purpose: Nanostructured lipid carriers were loaded with testosterone undecanoate (TU), which has a low oral bioavailability. Methods: Different NLC dispersions were produced using the hot high pressure homogenization method. Particles were characterized using dynamic and static light scattering techniques, differential scanning calorimetry and X-ray diffraction. And the bioavailability was compared to a marketed product. Results: Nanostructured lipid carriers with up to 30% TU load and sizes of about 600 and 200 nm could be achieved, allowing a direct comparison of the size effect in in vivo bioavailability studies. The zeta potentials varied between − 20 and − 40 mV. The bioavailability of Andriol Testocaps® in the fed state was matched. Conclusions: This opens the perspective of administering a single dose of dose of TU in one oral dosage unit and simultaneously having a bioavailability less dependent on the fed state.

Effect of surfactants on the formation and characterization of a new type of colloidal drug delivery system: Nanostructured lipid carriers

Nanostructured lipid carriers (NLC) consisted of solid lipid and liquid lipid are a new type of colloidal drug delivery system, which offer the advantage of improved drug loading capacity and release properties. Surfactants play important roles in the formation and characterization of NLC. In order to investigate the influence of surfactants on properties of NLC, four types of surfactants and their mixtures were used in the absence of model drugs thereby avoiding the interaction between surfactants and drugs. The hot high-pressure homogenization method was employed to produce NLC and the physicochemical properties of NLC, such as particle size distribution, zeta potential and DSC analysis were investigated. The results indicated that ionic surfactants such as sodium deoxycholate (SDC), showed obviously low emulsification efficiency in the preparation. However, it increased the zeta potential of nanoparticles leading to improve the physical stability of the system. Non-ionic emulsifier, especially Poloxamer 188, offered additional steric stabilization effect avoiding aggregation of the nanoparticles in the colloidal system. The formulation in the study combined four types of additives including ionic surfactant (SDC), non-ionic emulsifier (Poloxamer 188 and Tween-80), and Lecithin to obtain favorably stable NLC drug delivery system, which could stabilize for more than 1 year without phase separation at 4 °C.