The Experts below are selected from a list of 12663 Experts worldwide ranked by ideXlab platform
Xiangliang Yang - One of the best experts on this subject based on the ideXlab platform.
-
the research on the anti inflammatory activity and hepatotoxicity of triptolide loaded Solid Lipid Nanoparticle
Pharmacological Research, 2005Co-Authors: Zhinan Mei, Xiangliang YangAbstract:Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activity. However, its clinical use was restricted to some extent due to its serious toxicity. The possible mechanism for triptolide-induced hepatotoxicity was related to reactive oxygen species (ROS) inducing Lipid peroxidation and DNA damage. The development of controlled release delivery strategies could lead to significant advantages in the clinical use of these drugs to decreasing the toxicity. Thus, the present study was focused on the preparation and some characterization of triptolide-loaded Solid Lipid Nanoparticle (SLN) and the measurements of anti-inflammatory activities and the hepatotoxicity of TP-SLN. The carrageenan-induced rat paw edema experiment indicated that the anti-inflammatory activities of TP-SLN were stronger than those of free triptolide. Orally administration of TP-SLN 0.2 or 0.4 mg/kg per day did not cause mortality within the period of observation. In contrast, free triptolide at different doses had caused partial death. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly elevated in the free triptolide-treated group whereas they did not significantly change in TP-SLN-treated mice. The free triptolide increased malondialdehyde (MDA) level and decreased activities of superoxide dismutase (SOD) and total glutathione peroxidase (GSH-Px) in the liver homogenates. However, these phenomena were not found in TP-SLN-treated mice. The results of histopathological evaluation revealed a protective effect of SLN on vacuolation, edema, inflammatory infiltration and necrosis caused by triptolide. Furthermore, TP-SLN did not change Bcl/Bax protein ratio or decrease FasL expression in liver cells. These results suggest that SLN delivery system can enhance the anti-inflammatory activity of triptolide meanwhile has a protective effect against triptolide-induced hepatotoxicity. The toxicity of TP-SLN to other tissues is under investigation.
-
triptolide loaded Solid Lipid Nanoparticle hydrogel for topical application
Drug Development and Industrial Pharmacy, 2005Co-Authors: Zhinan Mei, Xiangliang YangAbstract:Triptolide (TP) has been shown to have anti-inflammatory, antifertility, antineoplastic, and immunosuppressive activity. However, its clinical usage is limited to some extent due to its poor water solubility and toxicity. In order to use innovative ways to administer TP and to overcome or alleviate its disadvantages, controlled-release delivery systems such as Solid Lipid Nanoparticle(SLN(s)) have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery and anti-inflammatory activity were also evaluated. The results indicated that SLN could serve as an efficient promoter of TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN, consisted of tristearin glyceride, soybean lecithin, and PEG400MS, with a particle size of 123+/-0.9 nm, polydispersity index (PI) of 0.19, and zeta potential of -45 mV. When this SLN dispersion was incorporated into hydrogel, the nanoparticulate structure was maintained, and aggregation and gel phenomena of the particle could be avoided. The cumulative transdermal absorption rate in 12 h was 73.5%, whereas the conventional TP hydrogel was 45.3%. The anti-inflammatory effect is over two-fold higher than that of conventional TP hydrogel. Moreover, this SLN hydrogel consists of pharmaceutically acceptable ingredients, such as soybean lecithin and Lipid, and the Nanoparticle can improve safety and minimize the toxicity induced by TP.
-
Solid Lipid Nanoparticle and microemulsion for topical delivery of triptolide
European Journal of Pharmaceutics and Biopharmaceutics, 2003Co-Authors: Zhinan Mei, Huabing Chen, Ting Weng, Yajiang Yang, Xiangliang YangAbstract:Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activities. However, its clinical use is restricted to some content due to its poor water solubility and some toxic effects. In order to find innovative ways for administering TP and alleviating its disadvantages, the controlled release delivery systems such as Solid Lipid Nanoparticle (SLN) and microemulsion have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery capacity and anti-inflammatory activity were also evaluated. The results indicated that these SLN dispersions and microemulsions could serve as efficient promoters for the TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN dispersion consisted of 5% tristearin glyceride, 1.20% soybean lecithin and 3.60% polyethylene glycol (400) monosterate, while the best formulation of microemulsion consisted of 40% isopropyl myristate, 50% Tween-80: 1,2-propylene glycol (5:1, v/v) and water. The steady-state flux (Js) and permeability coefficient (Kp) of triptolide for the SLN dispersion of the first 6 h were 3.1+/-0.4 microg/cm2 per h and 0.0124+/-0.001 cm/h or 6.4+/-0.7 microg/cm2 per h and 0.0256+/-0.002 cm/h for the microemulsion, which was 3.45 and 7.02 times higher than those of triptolide solution, respectively. The anti-inflammatory activity of SLN dispersion was stronger than that of microemulsion in carrageenan induced rat paw edema. However, the results were the reverse in complete Frenud's adjuvant induced paw edema. Further investigations should be carried out on the toxicity of different formulations of triptolide to tissues.
Zhinan Mei - One of the best experts on this subject based on the ideXlab platform.
-
the research on the anti inflammatory activity and hepatotoxicity of triptolide loaded Solid Lipid Nanoparticle
Pharmacological Research, 2005Co-Authors: Zhinan Mei, Xiangliang YangAbstract:Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activity. However, its clinical use was restricted to some extent due to its serious toxicity. The possible mechanism for triptolide-induced hepatotoxicity was related to reactive oxygen species (ROS) inducing Lipid peroxidation and DNA damage. The development of controlled release delivery strategies could lead to significant advantages in the clinical use of these drugs to decreasing the toxicity. Thus, the present study was focused on the preparation and some characterization of triptolide-loaded Solid Lipid Nanoparticle (SLN) and the measurements of anti-inflammatory activities and the hepatotoxicity of TP-SLN. The carrageenan-induced rat paw edema experiment indicated that the anti-inflammatory activities of TP-SLN were stronger than those of free triptolide. Orally administration of TP-SLN 0.2 or 0.4 mg/kg per day did not cause mortality within the period of observation. In contrast, free triptolide at different doses had caused partial death. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly elevated in the free triptolide-treated group whereas they did not significantly change in TP-SLN-treated mice. The free triptolide increased malondialdehyde (MDA) level and decreased activities of superoxide dismutase (SOD) and total glutathione peroxidase (GSH-Px) in the liver homogenates. However, these phenomena were not found in TP-SLN-treated mice. The results of histopathological evaluation revealed a protective effect of SLN on vacuolation, edema, inflammatory infiltration and necrosis caused by triptolide. Furthermore, TP-SLN did not change Bcl/Bax protein ratio or decrease FasL expression in liver cells. These results suggest that SLN delivery system can enhance the anti-inflammatory activity of triptolide meanwhile has a protective effect against triptolide-induced hepatotoxicity. The toxicity of TP-SLN to other tissues is under investigation.
-
triptolide loaded Solid Lipid Nanoparticle hydrogel for topical application
Drug Development and Industrial Pharmacy, 2005Co-Authors: Zhinan Mei, Xiangliang YangAbstract:Triptolide (TP) has been shown to have anti-inflammatory, antifertility, antineoplastic, and immunosuppressive activity. However, its clinical usage is limited to some extent due to its poor water solubility and toxicity. In order to use innovative ways to administer TP and to overcome or alleviate its disadvantages, controlled-release delivery systems such as Solid Lipid Nanoparticle(SLN(s)) have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery and anti-inflammatory activity were also evaluated. The results indicated that SLN could serve as an efficient promoter of TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN, consisted of tristearin glyceride, soybean lecithin, and PEG400MS, with a particle size of 123+/-0.9 nm, polydispersity index (PI) of 0.19, and zeta potential of -45 mV. When this SLN dispersion was incorporated into hydrogel, the nanoparticulate structure was maintained, and aggregation and gel phenomena of the particle could be avoided. The cumulative transdermal absorption rate in 12 h was 73.5%, whereas the conventional TP hydrogel was 45.3%. The anti-inflammatory effect is over two-fold higher than that of conventional TP hydrogel. Moreover, this SLN hydrogel consists of pharmaceutically acceptable ingredients, such as soybean lecithin and Lipid, and the Nanoparticle can improve safety and minimize the toxicity induced by TP.
-
Solid Lipid Nanoparticle and microemulsion for topical delivery of triptolide
European Journal of Pharmaceutics and Biopharmaceutics, 2003Co-Authors: Zhinan Mei, Huabing Chen, Ting Weng, Yajiang Yang, Xiangliang YangAbstract:Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activities. However, its clinical use is restricted to some content due to its poor water solubility and some toxic effects. In order to find innovative ways for administering TP and alleviating its disadvantages, the controlled release delivery systems such as Solid Lipid Nanoparticle (SLN) and microemulsion have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery capacity and anti-inflammatory activity were also evaluated. The results indicated that these SLN dispersions and microemulsions could serve as efficient promoters for the TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN dispersion consisted of 5% tristearin glyceride, 1.20% soybean lecithin and 3.60% polyethylene glycol (400) monosterate, while the best formulation of microemulsion consisted of 40% isopropyl myristate, 50% Tween-80: 1,2-propylene glycol (5:1, v/v) and water. The steady-state flux (Js) and permeability coefficient (Kp) of triptolide for the SLN dispersion of the first 6 h were 3.1+/-0.4 microg/cm2 per h and 0.0124+/-0.001 cm/h or 6.4+/-0.7 microg/cm2 per h and 0.0256+/-0.002 cm/h for the microemulsion, which was 3.45 and 7.02 times higher than those of triptolide solution, respectively. The anti-inflammatory activity of SLN dispersion was stronger than that of microemulsion in carrageenan induced rat paw edema. However, the results were the reverse in complete Frenud's adjuvant induced paw edema. Further investigations should be carried out on the toxicity of different formulations of triptolide to tissues.
Zhengrong Cui - One of the best experts on this subject based on the ideXlab platform.
-
Effect of a Solid Lipid Nanoparticle Formulation on the Bioavailability of 4-(N)-Docosahexaenoyl 2′, 2′-Difluorodeoxycytidine After Oral Administration
AAPS PharmSciTech, 2020Co-Authors: Solange A. Valdes, Riyad F. Alzhrani, Dharmika S. P. Lansakara-p, Zhengrong CuiAbstract:Previously, we developed a Solid Lipid Nanoparticle (SLN) formulation of 4-( N )-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC), a compound with promising antitumor activity. Herein, we studied the feasibility of administering the DHA-dFdC by the oral route using the Solid Lipid Nanoparticles ( i.e. , DHA-dFdC-SLNs). In simulated gastrointestinal fluids, the DHA-dFdC-SLNs did not aggregate. The release of the DHA-dFdC from the Solid Lipid Nanoparticles in simulated gastrointestinal fluid was slow, but was slightly faster in simulated intestinal fluid than in simulated gastric fluid. In mice orally administered with DHA-dFdC-SLNs, plasma DHA-dFdC concentration vs. time curve has a T_max of ~ 1.7 h and a C_max of 17.01 μg/mL. The absolute oral bioavailability of DHA-dFdC when given as DHA-dFdC-SLNs was ~ 68% (based on AUC_0–24 h values), while the relative oral bioavailability DHA-dFdC (compared with DHA-dFdC in a Tween 80/ethanol-in-water solution) was 126%. Finally, in mice with pre-establish B16-F10 murine melanoma, oral DHA-dFdC-SLNs increased their survival significantly, as compared with oral administration of the DHA-dFdC solution. It is concluded that the Solid Lipid Nanoparticle formulation increased the bioavailability of the DHA-dFdC upon oral administration, as compared with the DHA-dFdC solution.
-
effect of a Solid Lipid Nanoparticle formulation on the bioavailability of 4 n docosahexaenoyl 2 2 difluorodeoxycytidine after oral administration
Aaps Pharmscitech, 2020Co-Authors: Solange A. Valdes, Riyad F. Alzhrani, Dharmika S P Lansakarap, Zhengrong CuiAbstract:Previously, we developed a Solid Lipid Nanoparticle (SLN) formulation of 4-(N)-docosahexaenoyl 2', 2'-difluorodeoxycytidine (DHA-dFdC), a compound with promising antitumor activity. Herein, we studied the feasibility of administering the DHA-dFdC by the oral route using the Solid Lipid Nanoparticles (i.e., DHA-dFdC-SLNs). In simulated gastrointestinal fluids, the DHA-dFdC-SLNs did not aggregate. The release of the DHA-dFdC from the Solid Lipid Nanoparticles in simulated gastrointestinal fluid was slow, but was slightly faster in simulated intestinal fluid than in simulated gastric fluid. In mice orally administered with DHA-dFdC-SLNs, plasma DHA-dFdC concentration vs. time curve has a Tmax of ~ 1.7 h and a Cmax of 17.01 μg/mL. The absolute oral bioavailability of DHA-dFdC when given as DHA-dFdC-SLNs was ~ 68% (based on AUC0-24 h values), while the relative oral bioavailability DHA-dFdC (compared with DHA-dFdC in a Tween 80/ethanol-in-water solution) was 126%. Finally, in mice with pre-establish B16-F10 murine melanoma, oral DHA-dFdC-SLNs increased their survival significantly, as compared with oral administration of the DHA-dFdC solution. It is concluded that the Solid Lipid Nanoparticle formulation increased the bioavailability of the DHA-dFdC upon oral administration, as compared with the DHA-dFdC solution.
-
a Solid Lipid Nanoparticle formulation of 4 n docosahexaenoyl 2 2 difluorodeoxycytidine with increased solubility stability and antitumor activity
International Journal of Pharmaceutics, 2019Co-Authors: Solange A. Valdes, Riyad F. Alzhrani, Dharmika S P Lansakarap, Andres Rodriguez, Sachin G Thakkar, Zhengrong CuiAbstract:Abstract Previously, we synthesized 4-(N)-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC), a novel lipophilic compound with a potent, broad-spectrum antitumor activity. Herein, we report a Solid Lipid Nanoparticle (SLN) formulation of DHA-dFdC with improved apparent aqueous solubility, chemical stability, as well as efficacy in a mouse model. The SLNs were prepared from lecithin/glycerol monostearate-in-water emulsions emulsified with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Tween 20. The resultant DHA-dFdC-SLNs were 102.2 ± 7.3 nm in diameter and increased the apparent solubility of DHA-dFdC in water to at least 5.2 mg/mL, more than 200-fold higher than its intrinsic water solubility. DHA-dFdC in a lyophilized powder of DHA-dFdC-SLNs was significantly more stable than the waxy Solid of pure DHA-dFdC. DHA-dFdC-SLNs also showed an increased cytotoxicity against certain tumor cells than DHA-dFdC. The plasma concentration of DHA-dFdC in mice intravenously injected with DHA-dFdC-SLNs in dispersion followed a bi-exponential model, with a half-life of ~44 h. In mice bearing B16-F10 murine melanoma, DHA-dFdC-SLNs were significantly more effective than DHA-dFdC in controlling the tumor growth. In addition, histology evaluation revealed a high level of apoptosis and tumor encapsulation in tumors in mice treated with DHA-dFdC-SLNs. DHA-dFdC-SLNs represents a new DHA-dFdC formulation with improved antitumor activity.
-
Solid Lipid Nanoparticle formulations of docetaxel prepared with high melting point triglycerides in vitro and in vivo evaluation
Molecular Pharmaceutics, 2014Co-Authors: Youssef W Naguib, Leticia B Rodriguez, Stephen D Hursting, Robert O Williams, Zhengrong CuiAbstract:Docetaxel (DCX) is a second generation taxane. It is approved by the U.S. Food and Drug Administration for the treatment of various types of cancer, including breast, non-small cell lung, and head and neck cancers. However, side effects, including those related to Tween 80, an excipient in current DCX formulations, can be severe. In the present study, we developed a novel Solid Lipid Nanoparticle (SLN) composition of DCX. Trimyristin was selected from a list of high melting point triglycerides as the core Lipid component of the SLNs, based on the rate at which the DCX was released from the SLNs and the stability of the SLNs. The trimyristin-based, PEGylated DCX-incorporated SLNs (DCX-SLNs) showed significantly higher cytotoxicity against various human and murine cancer cells in culture, as compared to DCX solubilized in a Tween 80/ethanol solution. Moreover, in a mouse model with pre-established tumors, the new DCX-SLNs were significantly more effective than DCX solubilized in a Tween 80/ethanol solution in inhibiting tumor growth without toxicity, likely because the DCX-SLNs increased the concentration of DCX in tumor tissues, but decreased the levels of DCX in major organs such as liver, spleen, heart, lung, and kidney. DCX-incorporated SLNs prepared with one or more high-melting point triglycerides may represent an improved DCX formulation.
Wenzhong Zhou - One of the best experts on this subject based on the ideXlab platform.
-
Preparation, characterisation and antibacterial activity of a florfenicol-loaded Solid Lipid Nanoparticle suspension
IET Nanobiotechnology, 2015Co-Authors: Ting Wang, Xiaojin Chen, Mengmeng Lu, Xihe Li, Wenzhong ZhouAbstract:A florfenicol-loaded Solid Lipid Nanoparticle (FFC-SLN) suspension was prepared by hot homogenisation and ultrasonic technique. The suspension was characterised for its release profile, stability, toxicity, and the physicochemical properties of the Nanoparticles. Antibacterial activity of the suspension was evaluated in vitro and in vivo. The results showed that the mean diameter, polydispersity index and zeta potential of the Nanoparticles were 253 ± 3 nm, 0.409 ± 0.022 and 47.5 ± 0.21 mV, respectively. In vitro release profile showed the FFC-SLN suspension had sustained release effect. The minimum inhibition concentration values of the FFC-SLN suspension were 6 and 3 μg/mL against Staphylococcus aureus and Escherichia coli respectively, compared with 3.5 and 2 μg/mL of native florfenicol. The suspension was relatively stable at 4°C and less stable at room temperature during 9 months storage. Although the Nanoparticle carriers exhibited cytotoxicity in cell cultures, the LD50 of the lyophilised dry power of the suspension was higher than 5 g/kg body weight. Mortality protection against E. coli lethal infection in mice showed that the Nanoparticle suspension had much better efficacy (6/10) than native drug (1/10). These results indicate that FFC-SLN suspension could be a promising formulation in veterinary medicine.
-
preparation and stability study of norfloxacin loaded Solid Lipid Nanoparticle suspensions
Colloids and Surfaces B: Biointerfaces, 2012Co-Authors: Yan Wang, Xiaojin Chen, Luyan Zhu, Zhao Dong, Shuyu Xie, Xiaofang Wang, Wenzhong ZhouAbstract:This work aims to develop norfloxacin-loaded Solid Lipid Nanoparticle (NFX-SLN) suspensions as a novel formulation. NFX-SLN suspensions were prepared by hot homogenization and ultrasonic technique. The stability of the suspensions was studied after stored at 4°C and room temperature from 3 to 9 months. The physicochemical characteristics of the NFX-SLN, in vitro release patterns, in vitro antibacterial activity and in vivo therapeutic efficacy in mice after infection with Escherichia coli were conducted and used to evaluate the stability of the suspension. The results showed that the mean diameter (MD), polydispersity index (PDI), zeta potential (ZP) and loading capacity (LC) of Nanoparticles were 250±5 nm, 0.256±0.065, -31.1±1.85 mV and 9.63±0.16%, respectively. After 9 months of storage at 4°C, the NFX-SLN showed no significant changes in MD, PDI and LC except a miner change in ZP. Moreover, the stored suspension displayed same sustained release patterns and in vitro sustained bactericidal activities as that of the fresh preparation. In vivo therapeutic results revealed that the stored suspension had similar enhanced therapeutic efficacy as the fresh preparation compared with native drug. At room temperature the formulation was stable for 3 months, but the LC, ZP and PDI changed and the suspension displayed accelerated release and weakened in vitro antibacterial activity after 6 months. These results demonstrate that NFX-SLN suspensions could be a promising formulation for enhanced pharmacological activity of norfloxacin and were stable at 4°C and less stable at room temperature.
-
Solid Lipid Nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm
International Journal of Nanomedicine, 2011Co-Authors: Shuyu Xie, Baoliang Pan, Baoxin Shi, Zhuangzhi Zhang, Xu Zhang, Ming Wang, Wenzhong ZhouAbstract:Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ) against tapeworm, PZQ-loaded hydrogenated castor oil Solid Lipid Nanoparticle (PZQ-HCO-SLN) suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the Nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and −11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91.55%, 87.5%, and 66.7%. When the dose reduced to 0.5 mg/kg, the native drug showed no effect, but the suspension still got the same therapeutic efficacy as that of the 5 mg/kg native PZQ. These results demonstrate that the PZQ-HCO-SLN suspension is a promising formulation to enhance the therapeutic efficacy of PZQ.
Maria Angeles Solinis - One of the best experts on this subject based on the ideXlab platform.
-
gene delivery in the cornea in vitro ex vivo evaluation of Solid Lipid Nanoparticle based vectors
Nanomedicine: Nanotechnology Biology and Medicine, 2018Co-Authors: Monica Vicentepascual, Andrea Albano, Maria Angeles Solinis, Loredana Serpe, Alicia Rodriguezgascon, Federica Foglietta, Elisabetta Muntoni, Josune Torrecilla, Ana Del PozorodriguezAbstract:Aim Inflammation is a process that underlies sight-threatening ocular surface diseases, and gene supplementation with the plasmid that encodes for p-IL10 will allow the sustained de novo synthesis of the cytokine to occur in corneal cells, and provide a long-term anti-inflammatory effect. This work describes the development of Solid Lipid Nanoparticle systems for the delivery of p-IL10 to transfect the cornea. Results In vitro, vectors showed suitable features as nonviral vectors (size, ζ-potential, DNA binding, protection and release), and they were able to enter and transfect human corneal epithelial cells. Ex vivo, the vectors were found to transfect the epithelium, the stroma and the endothelium in rabbit corneal explants. Distribution of gene expression within the cell layers of the cornea depended on the composition of the four vectors evaluated. Conclusion Solid Lipid Nanoparticle-based vectors are promising gene delivery systems for corneal diseases, including inflammation.
-
a proline rich peptide improves cell transfection of Solid Lipid Nanoparticle based non viral vectors
Journal of Controlled Release, 2009Co-Authors: A Del Pozorodriguez, Maria Angeles Solinis, Silvia Pujals, Diego Delgado, A R Gascon, Ernest Giralt, J L PedrazAbstract:Abstract The aim of this work was to improve the transfection efficacy of Solid Lipid Nanoparticle (SLN)-based non-viral vectors into ARPE-19 cells through the addition of Sweet Arrow Peptide (SAP). First, we prepared SAP–DNA complexes at ratios of at least 50:1, and then incorporated them into the SLNs. All formulations were able to protect DNA, and the peptide favoured the most bioactive form (supercoiled) of open circular DNA turns. In vitro transfection studies of the vectors containing the pCMS-EGFP plasmid in HEK293 and ARPE-19 cell lines revealed that incorporation of SAP led to greater transfection in both cell lines, although via different mechanisms. The presence of SAP in the formulations did not affect the viability of HEK293 or ARPE-19 cells. In HEK293 cells, SAP enabled greater uptake of the vectors, and an SAP to DNA ratio of 50:1 was sufficient for enhancing transfection. In contrast, in ARPE-19 cells, SAP induced a change in the dominant entrance mechanism, from clathrin endocytosis to caveolae/raft-dependent endocytosis, thereby decreasing use of the lysosomal pathway and consequently, reducing vector degradation. The extent to which SAP uses one mechanism or the other largely depends on its concentration in the formulation.
