Paclitaxel-loaded glyceryl palmitostearate nanoparticles: in vitro release and cytotoxic activity

Solid lipid nanoparticles (SLNs) of paclitaxel using glyceryl palmitostearate (GPS) as matrix were prepared by modified hot homogenization method. The SLNs were characterized for mean particle size, percent entrapment efficiency, and zeta potential, which were found to be 207 nm, 96.26%, and ?28.26 mV, respectively. Transmission electron microscopic studies revealed that the prepared SLNs were of spherical shape. Drug retarding efficiency of the lipid (GPS) was better in pH 7.4 compared with pH 3.5. The release profile showed tendency to follow Higuchi diffusion pattern in both the media. Chemosensitivity assay carried out using B16F10 cell lines showed that antiproliferative activity of paclitaxel was not hindered because of encapsulation.     

Cyclosporine a loaded solid lipid nanoparticles: optimization of formulation, process variable and characterization

Solid lipid nanoparticles (SLNs) loaded with Cyclosporine A using glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) as lipid matrices were prepared by melt-homogenization using high-pressure homogenizer. Various process parameters such as homogenization pressure, homogenization cycles and formulation parameters such as ratio of drug: lipid, emulsifier: lipid and emulsifier: co-emulsifier were optimized using particle size and entrapment efficiencies as the dependent variables. The mean particle size of optimized batches of the GMS SLN and GPS SLN were found to be 131 nm and 158 nm and their entrapment efficiencies were 83 +/- 3.08% and 97 +/- 2.59% respectively. To improve the handling processing and stability of the prepared SLNs, the SLN dispersions were spray dried and its effect on size and reconstitution parameters were evaluated. The spray drying of SLNs did not significantly alter the size of SLNs and they exhibited good redispersibility. Solid state studies such as Infra Red Spectroscopy and Differential Scanning Calorimetry indicated absence of any chemical interaction between Cyclosporine A and the lipids. Scanning Electron Microscopy of optimized formulations showed spherical shape with smooth and non porous surface. In vitro release studies revealed that GMS based SLNs released the drug faster (41.12% in 20 hours) than GPS SLNs (7.958% in 20 hours). Release of Cyclosporine A from GMS SLN followed Higuchi equation better than first order while release from GPS SLN followed first order better than Higuchi model.     

Oral Apomorphine Delivery from Solid Lipid Nanoparticles with Different Monostearate Emulsifiers: Pharmacokinetic and Behavioral Evaluations

Apomorphine, a dopamine receptor agonist for treating Parkinson's disease, has very poor oral bioavailability (< 2%) due to the first-pass effect. The aim of this work was to investigate whether the oral bioavailability and brain regional distribution of apomorphine could be improved by utilizing solid lipid nanoparticles (SLNs). Glyceryl monostearate (GMS) and polyethylene glycol monostearate (PMS) were individually incorporated into SLNs as emulsifiers. It was found that variations in the emulsifiers had profound effects on the physicochemical characteristics. Mean diameters of the GMS and PMS systems were 155 and 63 nm, respectively. More than 90% of the apomorphine was entrapped in the SLNs. The interfacial film was the likely location for most of apomorphine molecules. The PMS system, when incubated in simulated intestinal medium, was found to be more stable in terms of particle size and encapsulation efficiency than the GMS system. Using the GMS and PMS systems to orally administer apomorphine (26 mg/kg) equally enhanced the bioavailability in rats. SLNs showed 12- to 13-fold higher bioavailability than the reference solution. The drug distribution in the striatum, the predominant site of therapeutic action, also increased when using the SLNs. The anti-Parkinsonian activity of apomorphine was evaluated in rats with 6-hydroxydopamine-induced lesions, a model of Parkinson's disease. The contralateral rotation behavior was examined after oral apomorphine delivery. The total number of rotations increased from 20 to 94 and from 20 to 115 when the drug was administered from SLNs containing GMS and PMS, respectively. The experimental results suggest that SLNs may offer a promising strategy for apomorphine delivery via oral ingestion.     

Transferrin-conjugated solid lipid nanoparticles for enhanced delivery of quinine dihydrochloride to the brain

Transferrin (Tf)-conjugated solid lipid nanoparticles (SLNs) were investigated for their ability to deliver quinine dihydrochloride to the brain, for the management of cerebral malaria. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidyl choline (HSPC), triolein, cholesterol and distearylphosphatidylethanolamine (DSPE). Coupling of SLNs with Tf was achieved by incubation of Tf with quinine-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) hydrochloride in phosphate buffered saline (pH 7.4) as a cross-linker. SLNs were characterized for shape, particle size, polydispersity and percentage drug entrapment. The SLNs were 108-126 nm in size, and maximum drug entrapment was 38.4-42.7%. Average size increased on coupling with Tf but percentage drug entrapment was reduced. The in-vitro release profile was determined using a dialysis technique; non-conjugated SLNs released comparatively more drug than Tf-SLNs. Fluorescence studies revealed enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs. In in-vivo performance studies, quinine plasma level and tissue distribution after intravenous administration of drug-loaded Tf-SLNs and unconjugated SLNs was compared with that of free drug. Intravenous administration of quinine dihydrochloride solution resulted in much higher concentrations of drug in the serum than with SLNs. Conjugation of SLNs with Tf significantly enhanced the brain uptake of quinine which was shown by the recovery of a higher percentage of the dose from the brain following administration of Tf-coupled SLNs compared with unconjugated SLNs or drug solution.     

Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate

Objectives The aims of this study were to evaluate the suitability of the spray congealing technique to produce solid lipid microparticles (SLMs) for topical administration and to study the skin permeation of a drug from SLMs compared with solid lipid nanoparticles (SLNs). Methods Econazole nitrate was used as model drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared at 5: 1, 10: 1 and 12.5: 1 lipid: drug weight ratios and characterised in terms of particle size, morphology, encapsulation efficiency and chemical analysis of the particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels for ex‐vivo drug permeation tests using porcine epidermis. Key findings SLMs had particle sizes of 18–45 μm, while SLNs showed a mean diameter of 130–270 nm. The encapsulation efficiency was 80–100%. Permeation profiles of econazole nitrate were influenced by both particle size (significant difference until 9 h) and the amount of lipid. Conclusions The results confirm the usefulness of SLNs as carriers for topical administration and suggest the potential of SLMs for the delivery of drugs to the skin.     

米非司酮固体脂质纳米粒的性状研究

制备并考察了米非司酮固体脂质纳米粒(SLN).结果表明,所得制品呈圆球状,粒径较均匀;x射线衍射分析表明SLN中米非司酮主要以无定形结构为主;差示扫描量热法结果表明,在较高药脂比时,SLN分散系中的药物仍以高分散状态存在.     

Impact of particle size and pH on protein corona formation of solid lipid nanoparticles: A proof-of-concept study

When nanoparticles were introduced into the biological media, the protein corona would be formed, which endowed the nanoparticles with new bio-identities. Thus, controlling protein corona formation is critical to in vivo therapeutic effect. Controlling the particle size is the most feasible method during design, and the influence of media pH which varies with disease condition is quite important. The impact of particle size and pH on bovine serum albumin (BSA) corona formation of solid lipid nanoparticles (SLNs) was studied here. The BSA corona formation of SLNs with increasing particle size (120–480 nm) in pH 6.0 and 7.4 was investigated. Multiple techniques were employed for visualization study, conformational structure study and mechanism study, etc. “BSA corona-caused aggregation” of SLN2‒3 was revealed in pH 6.0 while the dispersed state of SLNs was maintained in pH 7.4, which significantly affected the secondary structure of BSA and cell uptake of SLNs. The main interaction was driven by van der Waals force plus hydrogen bonding in pH 7.4, while by electrostatic attraction in pH 6.0, and size-dependent adsorption was confirmed. This study provides a systematic insight to the understanding of protein corona formation of SLNs.KEY WORDS: Protein corona, Solid lipid nanoparticles, BSA corona-Caused aggregation, Nanoparticle-protein interaction, Size effect, Cell uptake, Medium pH, Conformational structure     

Development and characterization of itraconazole-loaded solid lipid nanoparticles for ocular delivery

Abstract

The purpose of this study was to investigate the feasibility of entrapping water-insoluble drug itraconazole into solid lipid nanoparticles (SLNs) for topical ocular delivery. The drug-loaded SLNs were prepared from stearic acid and palmitic acid using different concentrations of polyvinyl alcohol employed as emulsifier. SLNs were prepared by the melt-emulsion sonication and low temperature-solidification method and characterized for particle size, zeta potential, drug loading and drug entrapment efficiency. The mean particle size of SLNs prepared with stearic acid ranged from 139 to 199?nm, while the SLNs prepared with palmitic acid had particle size in the range of 126–160?nm. The SLNs were spherical in shape. Stearic acid-SLNs showed higher entrapment of drug compared with palmitic acid-SLNs. Differential scanning calorimetry (DSC) and X-ray diffraction measurements showed decrease in crystallinity of drug in the SLN formulations. The modified Franz-diffusion cell and freshly excised goat corneas were used to test drug corneal permeability. Permeation of itraconazole from stearic acid-SLNs was higher than that obtained with palmitic acid-SLNs. The SLNs showed clear zone of inhibition against Aspergillus flavus indicating antimicrobial efficacy of formulations.     

Galactosylated solid lipid nanoparticles with cucurbitacin B improves the liver targetability

This study intended to prepare liver-targeting solid lipid nanoparticles (SLNs) with a hepatoprotective drug, cucurbitacin B (Cuc B), using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA). The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The Cuc B-loaded galactosylated and conventional SLNs were successfully prepared by a high-pressure homogenization method. The two SLNs showed similar physical and pharmaceutical properties, including: the particle size measured by laser diffraction was 135?nm for galactosylated SLN (GalSLN) and 123?nm for conventional SLNs (CSLN); zeta potentials were ?31.6 mV (GalSLN) and ?34.3 mV(CSLN); in vitro release behavior of the two SLNs was similar, and both showed the biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards. In contrast, the two SLNs demonstrated a marked difference in in vitro cellular cytotoxicity and in vivo tissue distribution performances. The IC₅₀ values of Cuc B in the two SLNs were by far lower than those of Cuc B solution and further Cuc B-GalSLN had about half the IC₅₀ value of Cuc B-CSLN. These results indicated that the encapsulation of Cuc B in SLNs resulted in the enhancement of cytotoxic activity, and galactosyl ligand could further enhance the cellular accumulation and cytotoxicity of Cuc B. The weighted-average overall drug targeting efficiency (Te) was used to evaluate the liver targetability. Cuc B-GalSLN gave a relatively high (Te)_liver value of 63.6%, ～ 2.5-times greater than that of Cuc B-CSLN (25.3%) and Cuc B solution (23.8%). In summary, the incorporation of N-HLBA into SLNs significantly enhanced the liver targetability of Cuc B-loaded SLNs and GalSLN had a great potential as a drug delivery carrier for improved liver targetability.     

Lactoferrin-appended solid lipid nanoparticles of paclitaxel for effective management of bronchogenic carcinoma

Abstract

Lung cancer is a dreadful disease which claims to be more life threatening as compared to total sum up of colon, prostate and breast cancers. Thus, there is an urgent need to develop an effective delivery approach for its management. Paclitaxel (PTX) is one of the well-known choice as antineoplasitic agent used for the treatment of different types of human cancers such as non-small-cell lung, head and neck cancers, leukemia, breast, ovarian and melanoma. Lactoferrin (Lf), a “multifunctional protein” is crucial for natural immunity which is secreted by exocrine glands. Lf receptors are expressed on the apical surface on bronchial epithelial cells. These over-expressed LF receptors can be utilized for the transportation of Lf-conjugated drug or nanocarrier devices. The present study was aimed to develop PTX-loaded Lf-coupled solid lipid nanoparticles (SLNs) for the treatment of lung cancer. PTX-loaded SLNs were prepared, characterized and then coupled with Lf using carbodiimide chemistry. The formulations were characterized by transmission electron microscopy, particle size, polydispersity index and zeta potential, whereas Lf conjugation was confirmed by FT-IR and ¹H NMR and efficiency of prepared system was evaluated by in vitro, ex vivo and in vivo evaluations. The ex vivo cytotoxicity studies on human bronchial epithelial cell lines, BEAS-2B, revealed superior anticancer activity of Lf-coupled SLNs than plain SLNs and free PTX. In vivo biodistribution studies showed higher concentrations of PTX accumulated in lungs via Lf-coupled SLNs than plain SLNs and free PTX. These studies suggested that Lf-coupled PTX-loaded SLNs could be used as potential targeting carrier for delivering anticancer drug to the lungs with the minimal side effects.     

Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs

The purpose of this work was to improve the oral bioavailability of poorly soluble drugs by incorporation into solid lipid nanoparticles (SLNs). All-trans retinoic acid (ATRA) was used as a poorly soluble model drug. Different formulations of SLNs loaded with ATRA were successfully prepared by a high-pressure homogenization method and using Compritol 888 ATO as lipid matrix. The particle size and distribution, drug loading capacity, drug entrapment efficiency (EE %), zeta potential, and long-term physical stability of the SLNs were investigated in detail. Drug release from two sorts of ATRA-SLN was studied and compared with the diffusion from ATRA solution in 0.1 M HCl, distilled water and phosphate buffer (pH 7.40), using a dialysis bag method. A pharmacokinetic study was conducted in male rats after oral administration of 8 mg kg(-1) ATRA in different formulations and it was found that the relative bioavailability of ATRA in SLNs was significantly increased compared with that of an ATRA solution. The amount of surfactant also had a marked effect on the oral absorption of ATRA with SLN formulations. Although an emulsion formulation also increased ATRA absorption, it was too unstable for use in clinical situations. The absorption mechanism of the SLN formulations was discussed. These results indicate that ATRA absorption is enhanced significantly by employing SLN formulations. SLNs offer a new approach to improve the oral bioavailability of poorly soluble drugs.     

Preparation and characteristic of vinorelbine bitartrate-loaded solid lipid nanoparticles

A hydrophilic and temperature-induced degradation drug, vinorelbine bitartrate (VB)-loaded solid lipid nanoparticles (SLNs) were prepared by a cold homogenization technique. The physicochemical properties of the SLNs, with various lipid composition, drug content and altered homogenizing times, were investigated. The mean particle size of the SLNs ranged from 150 to 350 nm. The enhancement of lecithin content in lipid matrix resulted in smaller particle of SLNs. The atomic force microscopy (AFM) images displayed that the shape of the SLNs was irregular sphere with smooth surface. The drug entrapment efficiency (EE) could be improved with the increasing of lecithin or oleic acid content in lipid matrix, and reduced with the added amount of drug. The highest EE and drug loading capacity (DL) could reach up to 80 and 6.6%, respectively. The studies of drug release showed that the drug release could last for 48 h, and the rate was delayed by the addition of lecithin or oleic acid in the formulations. The physical stability experiment indicated that the SLNs were stable for 2 months under room temperature. Moreover, the cellular cytotoxicity of VB against MCF-7 cells could be improved by the entrapment of SLNs.     

Benzothieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines: synthesis, characterization, antimicrobial activity, and incorporation into solid lipid nanoparticles

Fused triazolothienopyrimidines were prepared from the corresponding 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile. These precursors were intern prepared by employing the Gewald's reaction. All the newly synthesized compounds were characterized by spectral and analytical data. Title compounds displayed promising antibacterial and antifungal activities. Compound 3h which exhibited good antimicrobial activity was incorporated into SLN and characterized for particle size, entrapment efficiency (EE%), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and in-vitro release studies. It showed narrow particle size distribution with high entrapment efficiency. In-vitro release study of compound loaded SLNs in phosphate buffer of pH 7.4, exhibited a biphasic pattern with an initial burst and prolonged release over 24 h.     

Brain targeted solid lipid nanoparticles for brain ischemia: preparation and in vitro characterization

This study aims at formulating solid lipid nanoparticles (SLNs) of Vinpocetine (VIN) to be used as a brain targeted sustained drug-delivery system. VIN is a derivative of vincamine alkaloid, used for chronic cerebral vascular ischemia. However, it suffers from low bioavailability and short half-life. Its oral bioavailability is recorded to be between 7 and 55%. Its elimination half-life is 1–2?h so it would be a good candidate for a sustained drug-delivery system. VIN SLNs were prepared using modified high shear homogenization followed by ultrasonication technique. The effect of incorporating different lipids at different concentrations of various surfactants was investigated. The VIN SLNs were characterized by entrapment efficiency percent (EE%), particle size distribution, zeta-potential, and cumulative released percent after 96?h. The EE% ranged between 83.34% ± 0.95–94.56% ± 0.11 due to the lipophilic character of VIN. The mean particle size measured ranged from 123 nm–464?nm. The cumulative released percent after 96?h ranged from 23.55% to 75.67% showing a controlled release profile. Formula (F32) composed of 5% glyceryl monostearate (GMS) and stabilized by 2% surfactant mixture [Tween 80, Pluronic F 68 (1:1)] was the most appropriate formula for brain delivery having EE% of 89.09% ± 1.49, zero-order release kinetics with cumulative released percent of 72.12% after 96?h, zeta-potential of –11.3?±?0.97 mV. It showed a unimodal size distribution with particle size ≈90?nm and polydispersity index of 0.121. The formula of choice in this study exhibited a zero-order sustained release profile and met the requirement for a brain targeted SLN so it could be a promising formula to deliver VIN to the brain.     

Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax

Solid lipid nanoparticles (SLNs) have been proposed as suitable colloidal carriers for delivery of drugs with limited solubility. Ketoprofen as a model drug was incorporated into SLNs prepared from a mixture of beeswax and carnauba wax using Tween 80 and egg lecithin as emulsifiers. The characteristics of the SLNs with various lipid and surfactant composition were investigated. The mean particle size of drug-loaded SLNs decreased upon mixing with Tween 80 and egg lecithin as well as upon increasing total surfactant concentration. SLNs of 75 ± 4 nm with a polydispersity index of 0.2 ± 0.02 were obtained using 1% (vol/vol) mixed surfactant at a ratio of 60:40 Tween 80 to egg lecithin. The zeta potential of these SLNs varied in the range of –15 to –17 (mV), suggesting the presence of similar interface properties. High drug entrapment efficiency of 97% revealed the ability of SLNs to incorporate a poorly water-soluble drug such as ketoprofen. Differential scanning calorimetry thermograms and high-performance liquid chromatographic analysis indicated the stability of nanoparticles with negligible drug leakage after 45 days of storage. It was also found that nanoparticles with more beeswax content in their core exhibited faster drug release as compared with those containing more carnauba wax in their structure.From the Clinical EditorKetoprofen as model drug was incorporated into solid lipid nanoparticles, which have been proposed as suitable colloidal carriers for delivery of drugs with limited solubility. High drug entrapment efficiency, stability of nanoparticles with negligible drug leakage and fast drug release can be accomplished using this technology.     

Preparation and characterization of solid lipid nanoparticles loaded with total flavones of Hippophae rhamnoides (TFH)

Solid lipid nanoparticles (SLNs) containing total flavones of Hippophae rhamnoides (TFH) were prepared by high-pressure homogenization (HPH), by both hot HPH and cold HPH. The influence of process parameters (lipid matrix, lipid concentration, carbohydrate type and its concentration) on the SLN size distribution, zeta potential, entrapment efficiency, crystal form, and in vitro release profile was investigated. The highest entrapment efficiency for TFH, at around 93%, was found for SLNs composed of TFH/Compritol 888 ATO in a 1:30 molar ratio and made by cold HPH. The advantages of TFH SLNs are the improved oral bioavailability of TFH and the prolonged mean retention time and drug release time.     

Synthesis, physico-chemical and biological characterization of a paclitaxel macromolecular prodrug.

Paclitaxel was attached to poly(hydroxyethylaspartamide) via a succinic spacer arm by a two-step protocol: (1) synthesis of 2'-O-succinyl-paclitaxel; (2) synthesis of PHEA-2'-O-succinyl-paclitaxel. The 2'-O-succinyl-paclitaxel derivative and the macromolecular conjugate were characterized by UV, IR, NMR and mass spectrometry analysis. The reaction yields were over 95% and the purity of products over 98%. Paclitaxel release and degradation from 2'-O-succinyl-paclitaxel occurred at a faster rate at pH 5.5 than 7.4. After 30 h of incubation at pH 5.5 and 7.4 the released free paclitaxel was about 40 and 20%, respectively. In plasma both drug release and degradation were found to occur at a higher rate than in buffer at pH 7.4 suggesting that an enzymatic mechanism could be involved. The paclitaxel release and degradation from PHEA-2'-O-succinyl-paclitaxel were negligible at pH 5.5 and 7.4 and very slow in plasma. Investigation carried out using murine myeloid cell line showed that the polymeric prodrug maintains partial pharmacological activity of paclitaxel. The DL50 of the conjugate (over 40 ng/ml) as compared to free paclitaxel (about 1 ng/ml) was correlated to the slow drug release. Finally a pharmacokinetic study carried out by intravenous inoculation of the macromolecular prodrug to mice demonstrated that the polymer conjugation modify dramatically the in vivo fate of the drug. The conjugate disappeared from the bloodstream much more quickly as compared to both free drug and naked polymer. Massive accumulation of bioconjugate in the liver (80% of the dose) was found to persist throughout 1 week.     

Solid lipid nanoparticles of diethylcarbamazine citrate for enhanced delivery to the lymphatics: in vitro and in vivo evaluation

Objectives: The major objective is to target diethylcarbamazine citrate (DEC) to the lymphatics and to increase its retention time. The effect of various excipients on the physicochemical characteristics of the nanoparticles was also studied.

Materials and methods: Solid lipid nanoparticles (SLNs) of DEC were prepared by ultrasonication by varying the concentrations of compritol 888 ATO, poloxamer 188 and soya lecithin. The SLNs were evaluated for size, shape, texture, surface charge, physical nature of the entrapped drug, entrapment efficiency and in vitro drug release. In vivo animal studies were carried out to estimate the pharmacokinetic parameters in blood and drug concentration in lymph after oral administration.

Results: The size of the spherical particles was in the range of 27.25 ± 3.43 nm to 179 ± 3.08 nm and a maximum entrapment efficiency of 68.63 ± 1.53% was observed. In vitro release studies in pH 7.4 PBS displayed a rapid release and the maximum time taken for the complete drug to release was 150 min. In vivo studies indicated an enhancement in the amount of drug that reached lymphatics when administered via SLNs.

Conclusion: Targeting of DEC to the lymphatics is possible through SLNs and the retention time in the lymphatics can also be enhanced.     

Preparation and characterization of nitrendipine solid lipid nanoparticles

Nitrendipine, a dihydropyridine calcium channel blocker, has very poor oral bioavailability (10-20%) due to first pass effect. Solid lipid nanoparticle (SLN) delivery systems of nitrendipine have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soy phosphatidylcholine 95%, poloxamer 188 and charge modifiers stearylamine and dicetyl phosphate. SLNs were prepared by hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperatures above the melting point of lipids. Optimization studies of process and formulation variables were carried out. Particle size and zeta potential were measured by photon correlation spectroscopy (PCS) using Malvern zetasizer. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies were performed to characterize state of drug and lipid modification. In vitro release studies were performed in phosphate buffer pH 6.8 using modified Franz diffusion cell. Stable nitrendipine SLNs of mean size range 79 to 213 nm and zeta potential -38.2 to +34.6 mV were developed. About 99% nitrendipine was entrapped in SLNs and were stable on storage at 4 and 25 degrees C. DSC and PXRD analyses revealed that nitrendipine is dispersed in SLNs in an amorphous state. The release pattern of drug is analyzed and found to follow Weibull distribution rather than first order and Higuchi equation.     

Evaluation of hypericin-loaded solid lipid nanoparticles: physicochemical properties, photostability and phototoxicity

Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200-300 nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (P<0.05), also, the thermal analysis using differential scanning calorimetry (DSC) indicated good compatibility between hypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure.