In vitro skin permeation and retention of paromomycin from liposomes for topical treatment of the cutaneous leishmaniasis

Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL). Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases. This could be attributed to the low skin penetration of PA. Liposomal formulations usually provide sustained and enhanced drug levels in skin. The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial. Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method. Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method. The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1). The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells. The PA entrapment in LUV liposomes (20.4 ± 2.2%) was higher than that observed for MLV liposomes (7.5 ± 0.9%). Drug entrapment was 41.9 ± 6.2% and 27.2 ± 2.4% for PC and PC:CH LUV, respectively. The skin permeation was 1.55 ± 0.31%, 1.29 ± 0.40%, 0.20 ± 0.08%, and 0.50 ± 0.19% for PC LUV, PC:CH LUV, empty LUV + PA and aqueous solution, respectively. Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.     

Hot melt extruded Aprepitant–Soluplus solid dispersion: preformulation considerations,stability and in vitro study

Context: Solubility limitation of BCS class II drugs pose challenges to in vitro release.

Objective: To investigate the miscibility of Aprepitant (APR) and Soluplus^® (SOL) for hot melt extrusion (HME) viability and improved in vitro release of APR.

Methods: Solubility parameters of APR and SOL from group contribution methods were evaluated. Heat–cool–heat differential scanning calorimetry (DSC) scans were assessed for determining the glass forming ability (GFA) and glass stability (GS) of APR. An optimum HME temperature was selected based on melting point depression in physical mixtures. Moisture sorption isotherms were collected using a dynamic vapor sorption (DVS) analyzer at 25?°C. A 1:4 APR:SOL physical mixture was extruded in a co-rotating 12?mm twin screw extruder and in vitro release was assessed in fasted state simulated intestinal fluid (FaSSIF) with 0.25% SLS. Extrudates were analyzed using TGA, DSC, XRD and FTIR.

Results: APR was classified as a class II glass former. APR and SOL had composition dependent miscibility based on Gibb’s free energy of mixing. Extrudate prepared using HME had an amorphous as well as a crystalline phase that showed good stability in accelerated stability conditions. Smaller particle size extrudates exhibited a higher % moisture uptake and in vitro release compared to larger particle size extrudates. Enhanced in vitro release of APR from extrudates was attributed to amorphization of APR, solubilization as well as crystal growth inhibition effect of SOL due to H-bond formation with APR.

Conclusions: A solid dispersion of APR with improved in vitro release was successfully developed using HME technology.     

Influence of One Quinolone on the Formation and the Physical Stability of Liposomes

Abstract

The influence of one quinolone on the formation and physical stability of phosphatidylcholine (PC) liposomes is described. Based on Photon Correlation Spectroscopy (PCS) measurements, namely mean diameter and polydispersity, the maximum proportion of quinolone which is compatible with liposome morphology and homogeneous population was established in 30% mole of drug in a PC matrix. This lead to a pharmaceutical formulation which includes the additive D-α-tocoferol as antioxidant, glycerol as a co-solvent and phosphatidylcholine-cholesterol (2:1, mole/mole) as the formal lipid matrix. Drug encapsualtions between 30–40% were found. The feasibility of the method to scale-up this liposome formulation is discussed in terms of PCS, efficiency of encapsulation and preliminary assays in vivo.     

聚硼硅氧烷与有机磷酸酯阻燃剂复配协同阻燃聚碳酸酯

将聚硼硅氧烷(PB)阻燃剂分别与三种有机磷酸酯(OPP)阻燃剂进行复配, 并将此复合阻燃剂添加到聚碳酸酯(PC)中制备了阻燃PC材料(FR-PC)。采用极限氧指数(LOI)和锥形量热分析研究了PB对OPP/PC体系的协同阻燃作用。结果表明: 阻燃剂总质量分数为5%时, 添加质量分数1.25%以上的PB可以提高OPP/PC体系的LOI; PB阻燃剂具有促进成炭的作用, 可使OPP/PC复合体系在燃烧过程中释放的烟、热以及CO有不同程度的降低, 燃烧过程趋于平缓, 尤其使体系的烟释放量显著降低, 三种OPP/PC阻燃体系的总烟释放量下降31.8%~51.0%, 大大降低了火灾的危害性; 添加适量PB能够提高OPP/PC体系的拉伸强度、弯曲强度及维卡软化点温度, 并且使PC复合阻燃材料的透光率有所提高, 保持了PC良好的透明性。     

Development of stabilized itraconazole nanodispersions by using high-gravity technique

Purpose: For large scale preparation of stabilized itraconazole (ITZ) nanodispersions to improve the dissolution rate.

Method: High-gravity technique was employed to produce ITZ nanodispersions.

Results: Stabilizer had a significant effect on the stability of drug nanoparticles. Hydroxypropylmethylcellulose was found to be the most effective stabilizer to prevent drug nanoparticles from aggregation. ITZ nanoparticles with an average size of 210?nm were obtained. Mannitol was the suitable carrier matrix for improving the flowability and the dissolution rate of ITZ nanodispersion. The effects of operating variables on the particle size distribution were investigated in detail. The stability of ITZ nanodispersions was characterized by scanning electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and in vitro dissolution studies. After 6 months storage, the nanodispersion showed unchanged particles size, morphology, crystal state, chemical structure, and dissolution. In vitro dissolution rate indicated that the nanodispersion could significantly enhance the dissolution rate when compared to the commercial available Sporanox capsules. The nanodispersion achieved 70% of drug dissolution in 10?min, whereas the Sporanox capsules only dissolved 20% during the same period.

Conclusion: This study demonstrated that high-gravity technique is a promising method for large scale production of nanodispersions to enhance the dissolution rate of poorly water-soluble drugs.     

Preparation and evaluation of floating tablets of pregabalin

Abstract

Floating tablets of pregabalin were prepared using different concentrations of the gums (xanthan gum and guar gum), Carbopol 974P NF and HPMC K100. Optimized formulations were studied for physical tests, floating time, swelling behavior, in vitro release studies and stability studies. In vitro drug release was higher for tablet batches containing guar and xanthan gum as compared to the batches containing Carbopol 974P NF. Tablet batches were subjected to stability studies and evaluated by different parameters (drug release, drug content, FTIR and DSC studies). The optimized tablet batch was selected for in vivo pharmacodynamic studies (PTZ induced seizures). The results obtained showed that the onset of jerks and clonus were delayed and extensor phase was abolished with time in treated groups. A significant difference (p?>?0.05) was observed in control and treated group behavior indicating an excellent activity of the formulation for a longer period (>12?h).     

Preparation of Coenzyme Q10 nanostructured lipid carriers for epidermal targeting with high-pressure microfluidics technique

Objective: The objective of this work was to prepare coenzyme Q10 loaded nanostructured lipid carriers (Q10-NLC) and evaluate its epidermal targeting effect.

Methods: Q10-NLC was prepared by high-pressure microfluidics technique. Formulations and preparation parameters were optimized with response surface design. Q10-NLC was characterized by PCS, TEM, DSC and PXRD. The penetration of Q10 from the Q10-NLC formulations through skins and into skins were evaluated in vitro using Franz diffusion cells fitted with SD rat skins. In vitro release, long-term stability and light stability were also evaluated.

Results: The results showed that the concentration of solid lipid and emulsifier in formulation had a significant influence on particle size. The optimized preparation parameters were magnetic stirring for 20?min, high stirring at 8000?rpm for 1?min and high-pressure microfluidics at 1200 bar for three cycles. The size of Q10-NLC prepared by optimized formulation and parameters was (151.7?±?2.31) nm, polydispersity (PDI) 0.144, ζ potential was (?44.1?±?1.68) mV, drug loading 2.51%, encapsulation efficiency 100%. In vitro release study, Q10-NLC showed fast release during the first 3 hours and prolonged release afterwards. In vitro skin permeation study, the accumulative uptake of Q10 in epidermal of Q10-NLC was 10.11 times over Q10 emulsion. After exposure to day light for 24 hours, the amount of Q10 in Q10-NLC decreased only 5.59%, while in Q10 emulsion decreased 24.61% and Q10-ethanol solution 49.74%.

Conclusion: Q10-NLC exhibited a significant epidermal targeting effect, which was proved to be a promising carrier for topical delivery of Q10.     

聚硼硅氧烷与有机磷酸酯阻燃剂复配协同阻燃PC

将聚硼硅氧烷(PB)阻燃剂分别与三种有机磷酸酯(OPP)阻燃剂进行复配,并将此复合阻燃剂添加到聚碳酸酯(PC)中制备了阻燃PC材料(FR-PC)。采用极限氧指数(LOI)和锥形量热分析研究了PB对OPP/PC体系的协效阻燃作用。结果表明,在阻燃剂总量为5%(质量分数)时,添加占阻燃剂总量25%(质量分数)以上的PB可以提高OPP/PC体系的LOI。PB阻燃剂具有促进成炭的作用,可使OPP/PC复合体系在燃烧过程中释放的烟、热以及CO有不同程度的降低,燃烧过程趋于平缓,尤其使体系的烟释放量显著降低,三种OPP/PC阻燃体系的总烟释放量分别下降30%~50%,大大降低了火灾的危害性。添加适量PB能够提高OPP/PC体系的拉伸强度、弯曲强度及维卡软化点温度,并且使PC复合阻燃材料的透光率有所提高,保持了PC良好的透明性。     

Mucoadhesive nanostructured lipid carriers (NLCs) as potential carriers for improving oral delivery of curcumin

Purpose: To examine effects of polymer types on the mucoadhesive properties of polymer-coated nanostructured lipid carriers (NLCs).

Experiment: Curcumin-loaded NLCs were prepared using a warm microemulsion technique followed by coating particle surface with mucoadhesive polymers: polyethylene glycol400 (PEG400), polyvinyl alcohol (PVA), and chitosan (CS). The physicochemical properties and entrapment efficacy were examined. In vitro mucoadhesive studies were assessed by wash-off test. In addition, the stability of mucoadhesive NLCs in gastrointestinal fluids and the pattern of drug release were also investigated.

Findings: The obtained nanoparticles showed spherical shape with size ranging between 200?nm and 500?nm and zeta potential between ?37 and ?9?mV depending on the type of polymer coating. Up to 80% drug entrapment efficacy was observed. In vitro mucoadhesive studies revealed that PEG-NLCs and PVA-NLCs were adhered strongly to freshly porcine intestinal mucosa, more than 2-fold mucoadhesive compared to CS-NLCs and uncoated-NLCs. The particle size of all polymer-coated NLCs could be maintained in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggesting good physical stability in physiological fluid. In contrast, uncoated-NLCs showed particle aggregation in SGF. In vitro dissolution studies revealed a fast release characteristic.     

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling,characterization, and ex vivo skin permeation

Objective: The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience.

Methods: TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3?×?2²-level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y₁), vesicle size (Y₂), polydispersity index (Y₃), and zeta potential (Y₄) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug–excipient interactions, and vesicle stability were also investigated.

Results: The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p?Conclusion: The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.     

Study of a novel disintegrable oleanolic acid-polyvinylpolypyrrolidone solid dispersion

Novel solid dispersions of oleanolic acid-polyvinylpolypyrrolidone (OLA-PVPP SDs) were designed and prepared to improve the apparent solubility of drug, as well as to improve the stability, fluidity and compressibility of SDs. Disintegrable OLA-PVPP SDs were then evaluated both in vitro and in vivo. DSC, XRD, IR and SEM analysis proved the formation of OLA-PVPP SD and its amorphous state. The results of fluidity study, moisture absorption test and stability test showed that OLA-PVPP SD with good fluidity and qualified stability was successfully obtained. Meanwhile excellent dissolution rate was achieved for in vitro studies; dissolution test showed that ～50–75% of OLA was dissolved from SDs within the first 10?min, which is about 10–15 times of free OLA. In vivo study indicated that the formation of solid dispersion could largely improve the absorption of OLA, resulting in a much shorter T_max (p?C_max (p?0→∞ of OLA-PVPP SDs (1:6) were 155.4?±?37.24?h·ng/mL compared to the 103.11?±?26.69?h·ng/mL and 94.92?±?13.05?h·ng/mL of OLA-PVPP physical mixture (1:6) and free OLA, respectively. These proved PVPP could be a promising carrier of solid dispersions and was industrially feasible alternative carrier in the manufacture of solid dispersions.     

Histopathological evaluation of caffeine-loaded solid lipid nanoparticles in efficient treatment of cellulite

Context: Cellulite refers to dimpled appearance of the skin, usually located in the thighs and buttocks regions of most adult women.

Objective: The aim of this study was to formulate topically used caffeine-loaded solid lipid nanoparticle (SLN) for the treatment of cellulite.

Methods: SLNs were prepared by hot homogenization technique using Precirol® as lipid phase. The physical characterization and stability studies of SLNs as well as in vitro skin permeation and histological studies in rat skin were conducted.

Results: The mean particle size, encapsulation efficiency and loading efficiency percentages for optimized SLN formulation were 94?nm, 86 and 28%, respectively. In vitro drug release demonstrated that caffeine-loaded SLN incorporated into carbopol made hydrogel (caffeine-SLN-hydrogel) exhibited a sustained drug release compared to the caffeine hydrogel over 24?h. Caffeine-loaded SLNs showed a good stability during 12 months of storage at room temperature. The DSC and XRD results showed that caffeine was dispersed in SLN in an amorphous state. In vitro permeation studies illustrated higher drug accumulation in the skin with caffeine-SLN-hydrogel compared to caffeine hydrogel. The flux value of caffeine through rat skin in caffeine-SLN-hydrogel was 3.3 times less than caffeine hydrogel, representing lower systemic absorption. In contrast with caffeine hydrogel, the histological studies showed the complete lysis of adipocytes by administration of caffeine-SLN-hydrogel in the deeper skin layers.

Conclusion: Results of this study indicated that SLNs are promising carrier for improvement of caffeine efficiency in the treatment of cellulite following topical application on the skin.     

Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride

The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Berberine hydrochloride (BBH), an important bioactive compound from Chinese Medicines with poor water solubility. Pseudoternary phase diagrams were constructed using oil, surfactant and co-surfactant types to identify the efficient self-microemulsification region. SMEDDS was characterized by morphological observation, droplet size, zeta-potential determination, stability, in vitro release and in vivo bioavailability study. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 40% (w/w) of ethyl linoleate and oleic acid (2:1), 35% (w/w) Tween-80 and 25% (w/w) glycerol. The SMEDDS of BBH could exhibit good stability. In vitro release test showed a complete release of BBH from SMEDDS was in 5 h. In vivo results indicated that the peak plasma concentration (C_max) and the area under the curve (AUC_{0→12 h}) of SMEDDS of BBH were higher than the commercial tablet by 163.4% and 154.2%, respectively. The relative bioavailability of SMEDDS of BBH was enhanced about 2.42-fold compared with the commercial tablet in rats. The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability.     

Potentials of proniosomes for improving the oral bioavailability of poorly water-soluble drugs

Objective: The objectives of this study were, first, to develop a free-flowing and stable proniosome formulation for poorly water-soluble drugs such as vinpocetine; and second, to estimate its bioavailability as oral drug delivery system.

Methods: The proniosomes consisting of span60, cholesterol, sorbitol and vinpocetine were prepared by a novel approach. After the proniosomes were contacted with water, the suspension of vinpocetine-loaded niosomes formed automatically. The proniosomes and reconstituted niosomes were evaluated for their physicochemical characteristics, in vitro drug dissolution and release, integrity and stability at different GI tract pH conditions, in situ single-pass intestinal perfusion and in vivo bioavailability.

Results: The proniosome powder exhibited excellent flowability. The reconstituted niosomes with high drug entrapment efficiency (89.67?±?3.28%) showed spherical morphology with smooth surface under transmission electron microscope (TEM). X-ray diffraction (XRD) indicated that the drug was in an amorphous or molecular state in proniosome powder. In vitro dissolution and release study, proniosomes did enhance the dissolution and release rate compared to vinpocetine suspension in phosphate buffer solution (pH 7.2). Proniosome-derived niosomes could keep their integrity and stability at different GI tract pH conditions. The in situ single-pass intestinal perfusion indicated that encapsulation of vinpocetine into niosomes could largely improved the absorption of vinpocetine. The AUC(0?∞) of F2 and F3 was about 4.0- and 4.9-fold higher than that of the vinpocetine suspension, respectively. The results demonstrated the proniosomes indeed remarkably enhanced the oral bioavailability of vinpocetine.

Conclusion: This study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosome carrier systems.     

Essential work of fracture testing of PC-rich PET/PC blends with and without transesterification catalysts

0.7 mm sheets of blends of polycarbonate (PC) with polyethylene terephthalate (PET) rich in PC in the presence and absence of three different transesterification catalysts have been obtained using reactive extrusion-calendering processing method in order to evaluate the fracture toughness of these materials applying the essential work of fracture (EWF) approach which has not been previously reported in the literature. The morphology has been characterized by scanning electron microscopy (SEM). In addition, the tensile properties of these materials were determined. There is a decrease on the essential term (w _e) values of PC/PET blends without transesterification catalysts while blends with transesterification catalysts present an increment in comparison with neat PC which may related to the product of the transesterification that plays like an emulsifier/compatibilizing agent to reduce the interfacial tension between the components of the blend and reduce the interfacial tension between the two immiscible or incompatible component phases to get a better fracture behavior. This is confirmed by the tensile test results obtained which demonstrate higher values for E and σ _y in the case of blends with transesterification catalysts compared with neat PC. For non-essential term of fracture (βw _p), blends without catalysts exhibit an increase compared with neat PC by increasing the amount of PET which may due to the lowering of the yielding stress. In contrary, the presence of transesterification catalysts and especially Zn-based shows decrease as a consequence of the restriction that occurred on the movement of PC segments during the transesterification reactions or as a decohesion of the dispersed phase during the test.     

Characterization of micellar systems produced by new amphiphilic conjugates of poly(ethylene glycol)

This study proposes polymeric micelles produced using new amphiphilic conjugates between amino- or carboxy-mPEG₂₀₀₀ and three different α-lipoamino acids (PEG-LAA). The characterization of these colloidal systems showed CMC values, in the order of 10^?5?M, that are interesting in the view of an in vivo administration. The PEG-LAA micelles also showed a good stability at 37?°C and upon dilution in aqueous media. Using a colored probe as a model lipophilic compound, the loading efficiency and in vitro release profile were also outlined.     

In vitro and in vivo evaluation of a desonide gel-cream photostabilized with benzophenone-3

Context: Our group previously reported the photoinstability of some desonide topical commercial formulations under direct exposure to UVA radiation.

Objective: This study aimed to prepare and characterize a gel-cream containing desonide, with greater photostability than the commercial gel-cream (C-GC). Benzophenone-3 (BP-3) was used as a photostabilizing agent.

Methods: The gel-cream developed (D-GC) containing BP-3 at 0.1% was prepared and characterized regarding its pH, drug content, spreadability, viscosity, in vitro drug release and in vitro permeation. The in vivo anti-inflammatory effect was assessed by ear edema measurement, croton oil-induced acute skin inflammation and myeloperoxidase assay.

Results and Discussion: D-GC presented characteristics compatible with topical application, appropriate drug content and good spreadability, and non-Newtonian behavior with pseudoplastic flow. D-GC showed a good photostability profile, presenting a desonide content of 95.70% after 48?h of exposure to UVA radiation, and stability under room conditions during 60 days. The amount of desonide released from D-GC and C-GC was 57.8 and 51.7?µg/cm², respectively, measured using the vertical Franz cell. The in vitro skin permeation showed that desonide reached the site of action of the topical corticosteroids, from both formulations; however, the desonide amount retained in the dermis was lower with D-GC. The in vivo evaluation of topical anti-inflammatory activity indicated that D-GC presented the same biological effect as C-GC.

Conclusion: D-GC represents a promising approach to treat dermatological disorders, since it presented satisfactory physicochemical characteristics, the same biological activity as C-GC and superior photostability, conferred by the addition of BP-3 at 0.1%.     

Use of CACO-2 Cells as an in vitro Intestinal Absorption and Metabolism Model

Abstract

The Caco-2 cell line, a human colorectal carcinoma cell line, is an established in vitro model for the study of drug transport in the human intestine. We have routinely utilized this in vitro model to 1) elucidate intestinal absorption mechanisms of small drug molecules and peptide-like therapeutic agents (e.g. paracellular/transcellular passive diffusion and carrier-mediated active transport), 2) screen and select orally active therapeutic agents, 3) identify optimum luminal pH's for drug absorptions, 4) address dissolution rate-related absorption problems, 5) assess mucosal toxicity of therapeutic agents, and 6) evaluate prodrug approaches for enhanced drug absorptions. We have also utilized this in vitro model to assess the metabolic stability of therapeutic agents in the intestinal epithelium. Demonstrated in this report are primarily the techniques for the elucidation of absorption mechanisms. Examples of the characterization of paracellular/ transcellular passive diffusion pathways and carrier-mediated active transport will be given. Application of the Caco-2 model to the process of drug development will also be discussed.     

Effect of liquid-to-solid lipid ratio on characterizations of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for transdermal administration

The aim of this study is to evaluate the effect of liquid-to-solid lipid ratio on properties of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and to clarify the superiority of NLCs over SLNs for transdermal administration. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, differential scanning calorimetry, X-ray diffractometry, in vitro percutaneous permeation profile, and stability of SLNs and NLCs were compared. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, and in vitro percutaneous permeation amount of the developed NLCs were all <200?nm, 78%, >35, and >240?μg/cm², respectively, however, for SLNs were 280?nm,??29.11?mV, 63.2%, 32.54, and 225.9?μg/cm², respectively. After 3 months storage at 4?°C and 25?°C, almost no significant differences between the evaluated parameters of NLCs were observed. However, for SLNs, particle size was increased to higher than 300?nm (4?°C and 25?°C), drug encapsulation efficiency was decreased to 51.2 (25?°C), in vitro occlusion factor was also decreased to lower than 25 (4?°C and 25?°C), and the cumulative amount was decreased to 148.9?μg/cm² (25?°C) and 184.4?μg/cm² (4?°C), respectively. And DSC and XRD studies indicated that not only the crystalline peaks of the encapsulated flurbiprofen disappeared but also obvious difference between samples and bulk Compritol® ATO 888 was seen. It could be concluded that liquid-to-solid lipid ratio has significant impact on the properties of SLNs and NLCs, and NLCs showed better stability than SLNs. Therefore, NLCs might be a better option than SLNs for transdermal administration.     

Effects of surface charge of low molecular weight heparin-modified cationic liposomes on drug efficacy and toxicity

Cationic liposome is a potential nanocarrier to deliver drugs to solid tumor with proven efficiency in targeting tumor tissues. However, the major limitation is their charge-related instability and blood toxicity via intravenous injection. In order to overcome these problems and to maintain tumor targeting potency, we modified the cationic liposomes with low molecular weight heparin (LMWH) to obtain series of liposomes with different surface charges. Both in vitro and in vivo studies including serum stability, blood hemolysis, cellular uptake, cytotoxicity and in vivo biodistribution were evaluated. The results indicated the cationic liposome with surface charge of 5?mV (denoted as LLip-C) had the similar stability in serum and mild hemocytolysis compared with that of anionic liposome (LLip-D), but better cellular uptake owing to electrostatic interaction between cationic liposomes and cell membranes. Furthermore, we prepared curcumin-loaded liposomes to investigate the therapy efficiency. The intracellular distribution of curcumin-loaded LLip-C (Curcumin-LLip-C) was inclined to locate in cytoplasm and nuclei than curcumin-loaded LLip-D (Curcumin-LLip-D). In vitro cytotoxicity of Curcumin-LLip-C also exhibited higher inhibition of tumor cells than that of Curcumin-LLip-D. These results certified that a slightly positive surface charge of nanocarriers could achieve the balance between well antitumor efficiency and mild adverse effects.