Objective:To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis(CE).Methods:ABZ and PZQ loaded solid lipid nanoparticles(SLNs) were prepared ...Objective:To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis(CE).Methods:ABZ and PZQ loaded solid lipid nanoparticles(SLNs) were prepared by high shear homogenization and microemulsion congealing techniques with some minor modification.Nanoparticles average size,polydispersity index(PDI),and particle size distribution were determined by scanning electron microscopy(SEM) and photon correlation spectroscopy.Forty females BALB/c were experimentally infected by protoscoleces(PSC) and randomly divided into four equal groups of 10 mice.After the end of the 3 months treatment period and 2 months rest,mice were sacrificed and the peritoneal cavity was opened for removal,counting,measuring,and histological analysis of hydatid cyst.Results:The results indicated that ABZ and PZQ chemoprophylaxis treatment reduced the wet weight and size of developed cysts 77.3% and 79%,respectively.The corresponding result for the ABZ and PZQ loaded SLNs was 83% and 85%,respectively.Conclusions:This study for the first time demonstrated that ABZ and PZQ loaded SLNs is superior to free ABZ and PZQ for the chemoprophylaxis of CE in mice.展开更多
The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsificati...The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant. Systematic screening of formulation factors was carried out. The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency, particle size and zeta potential as the indexes. The entrapment efficiency of the optimized formulation(methazolamide-chitosan-SLNs)prepared was(58.5± 4.5)%,Particle size(247.7 ± 17.3) nm and zeta potential(33.5 ±3.9) mV. Transmission electron microscopy showed homogeneous spherical particles in the nanometer range. A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution. No ocular damages were observed in the susceptibility test on albino rabbits. The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers, and chitosanSLNs is a potential carrier for ophthalmic administration.展开更多
Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. T...Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. The physical stability of the nanoparticles was investigated by zeta potential measurement and they were shown to be quite stable. Fluorescence spectroscopy confirmed that the loaded position of BSA was on the interface between the inner aqueous phase and the solid lipid phase. Both Fourier-transform infrared spectroscopy and circular dichroism spectra indicate that BSA in the nanoparticles was not destroyed, but the secondary structure was disrupted slightly.展开更多
Nanotechnology is a rapidly expanding discipline,and solid lipid nanoparticles(SLN)are at the forefront of this development.They offer various possible clinical and pharmaceutical research applications and numerous ot...Nanotechnology is a rapidly expanding discipline,and solid lipid nanoparticles(SLN)are at the forefront of this development.They offer various possible clinical and pharmaceutical research applications and numerous other fields.A quantitative review technique called bibliometric analysis uses statistics,data mining,and mathematics to find emerging trends in a particular academic topic.It is currently more widely utilized and is employed in many academic subjects.As a result,the current study looked through Scopus-indexed research documents on SLNs from 2012 to 2022 to assess the growth and expansion of this body of knowledge and predict its course in the future.The VOSviewer package and Scopus Analytics were used to conduct the bibliometric analysis.VOSviewer offers two distinct viewing modes:network and overlay visualization.A total of 3768 journal articles(n=3709)and conference papers(n=59)were extracted.The number of research documents published by 12,367 authors was steadily increasing annually.Gene therapy,development and detection methods,bioavailability,and controlled release have been important research subjects.Souto,E.B.,of the University of Porto in Portugal,is considered the most prolific and frequently cited scholar.Punjab University(India)is the top-publishing institution.India is the leading country in the number of publications and research collaborations.The International Journal of Pharmaceutics is the top source.The current results keep pace with global scientific efforts in nanotechnology and successfully integrate them into the pharmaceutical industry.展开更多
The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circum...The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.展开更多
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 ...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 infuence 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 signifcantly 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 p H 7.4,while by electrostatic attraction in pH 6.0,and size-dependent adsorption was confrmed.This study provides a systematic insight to the understanding of protein corona formation of SLNs.展开更多
In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion tech...In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size,zeta potential,drug entrapment efficiency,in vitro drug release,and stability.All parameters were found to be in an acceptable range.In vitro drug release was found to be 94.1674.78%after 24 h and was fitted to the Higuchi model with a very high correlation coefficient(R2¼0.9941).Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography.The brain/blood ratio at 0.5 h for HP-SLNs i.n.,HP sol.i.n.and HP sol.i.v.was 1.61,0.17 and 0.031,respectively,indicating direct nose-to-brain transport,bypassing the blood-brain barrier.The maximum concentration(Cmax)in brain achieved from i.n.administration of HP-SLNs(329.17720.89 ng/mL,Tmax 2 h)was significantly higher than that achieved after i.v.(76.9577.62 ng/mL,Tmax 1 h),and i.n.(90.1376.28 ng/mL,Tmax 2 h)administration of HP sol.The highest drug-targeting efficiency(2362.43%)and direct transport percentage(95.77%)was found with HP-SLNs as compared to the other formulations.Higher DTE(%)and DTP(%)suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.展开更多
The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally s...The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.展开更多
Objective To evaluate the difference of the pharmacokinetic(PK)and tissue distribution properties in mice administrated with lyophilized icariin stealth solid lipid nanoparticles(Ica-SSLN)modified by polyethylene glyc...Objective To evaluate the difference of the pharmacokinetic(PK)and tissue distribution properties in mice administrated with lyophilized icariin stealth solid lipid nanoparticles(Ica-SSLN)modified by polyethylene glycol and icariin control solution(Ica-Sol).Meanwhile,to establish a sensitive,specific,and stable HPLC method for the determination of Ica in mice plasma and various tissues.Methods Ica-SSLN was prepared by high temperature melt-cool solidification method.Particle size and Zeta potentials were measured by a ZetaPlus.After iv administration of Ica-SSLN and Ica-Sol at a single dose of 7.46 mg/kg,the blood and tissues including brain,liver,spleen,lung, heart,and kidney were collected at different time points.The obtained concentration from HPLC analysis was statistically treated to determine the PK model and the relevant PK parameters using DAS1.0.Tissue distribution studies of Ica-SSLN were carried out in Kunming mice after iv administration and compared to Ica-Sol.Results The characteristic data showed that the mean particle size of Ica-SSLN was(50.03±0.90)nm,entrapment efficiency was(71.67±1.09)%,and the particles carried negative charge,Zeta potential was(?22.77±1.89)mV.The concentration-time profiles of Ica in mice after iv administrated with Ica-SSLN and Ica-Sol were shown to fit a two-compartment open model.Compared with Ica-Sol,the t1/2βof Ica-SSLN was prolonged by seven times and the AUC was increased by four times.The levels of Ica concentration in the kidney tissues were significantly increased. In addition,compared with Ica-Sol,the relative target efficiency to kidney tissue was 79%and the relative tissue exposure was 16.95.Conclusion It demonstrates that Ica-SSLN has selective targeting to kidney tissue and the kidney targeted Ica-SSLN seems to have significant advantages and good development value.展开更多
Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal spontaneously.Bone tissue engineering is a promising strategy aimed at developing in vitro re...Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal spontaneously.Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts.In this study,we developed an innovative bone engineering scaffold based on gelatin methacrylate(GelMA)hydrogel,obtained via a two-step procedure:first,solid lipid nanoparticles(SLNs)were loaded with resveratrol(Res),a drug that can promote osteogenic differentiation and bone formation;these particles were then encapsulated at different concentrations(0.01%,0.02%,0.04%and 0.08%)in GelMA to obtain the final Res-SLNs/GelMA scaffolds.The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone regeneration in rat cranial defects were evaluated using various characterization assays.Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs,with the ideally slow and steady release of Res;the optimal scaffold was 0.02 Res-SLNs/GelMA.Therefore,the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility,osteoconduction and osteoinduction,thereby showing potential for application in bone tissue engineering.展开更多
Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. P...Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel (4 mg/kg) while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area (14%) and stenosis (22%) by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.展开更多
Background: Curcuminoids are promising cancer chemopreventive agents. Curcumin, demethoxycurcumin(DMC) and bisdemethoxycurcumin(BDMC) are the major bioactive curcuminoids in turmeric. However, comprehensive metabolic ...Background: Curcuminoids are promising cancer chemopreventive agents. Curcumin, demethoxycurcumin(DMC) and bisdemethoxycurcumin(BDMC) are the major bioactive curcuminoids in turmeric. However, comprehensive metabolic studies of these three curcuminoids are still limited.Objective: To identify the metabolites of curcumin, DMC and BDMC in rats after oral administration of solid lipid nanoparticles(SLNs).Methods: Male Sprague-Dawley rats(250 ± 20 g, body weight) were randomly divided into 4 groups(n=3), and were orally administered with curcumin-SLN, DMC-SLN, BDMC-SLN, or blank-SLN, respectively. Plasma samples(500 μL) via the angular vein were collected at 1, 2 and 4 h post dosing, and the urine and feces samples were collected at 0–12 h and 12–24 h post-intake. An HPLC-DAD-ESI-MSnmethod was developed to identify the metabolites. The structures of phase II metabolites were further confirmed by enzyme hydrolysis.Results: A total of 34 metabolites were identified in rats plasma, urine, and feces. Most of them were phase II metabolites, including glucuronide conjugates and sulfate conjugates. Among them, the glucuronide conjugates were the major metabolites in rats plasma. In the meanwhile, the three parent curcuminoids were detected in high amounts in the urine and feces samples.Conclusion: The possible metabolic pathways of curcuminoids in rats were proposed.展开更多
Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherap...Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.展开更多
基金supported by a grant from the INSF(Iran National Science Foundation,No.91055004)
文摘Objective:To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis(CE).Methods:ABZ and PZQ loaded solid lipid nanoparticles(SLNs) were prepared by high shear homogenization and microemulsion congealing techniques with some minor modification.Nanoparticles average size,polydispersity index(PDI),and particle size distribution were determined by scanning electron microscopy(SEM) and photon correlation spectroscopy.Forty females BALB/c were experimentally infected by protoscoleces(PSC) and randomly divided into four equal groups of 10 mice.After the end of the 3 months treatment period and 2 months rest,mice were sacrificed and the peritoneal cavity was opened for removal,counting,measuring,and histological analysis of hydatid cyst.Results:The results indicated that ABZ and PZQ chemoprophylaxis treatment reduced the wet weight and size of developed cysts 77.3% and 79%,respectively.The corresponding result for the ABZ and PZQ loaded SLNs was 83% and 85%,respectively.Conclusions:This study for the first time demonstrated that ABZ and PZQ loaded SLNs is superior to free ABZ and PZQ for the chemoprophylaxis of CE in mice.
基金supported by grants from the National Natural Science Foundation of China(81100977)
文摘The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant. Systematic screening of formulation factors was carried out. The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency, particle size and zeta potential as the indexes. The entrapment efficiency of the optimized formulation(methazolamide-chitosan-SLNs)prepared was(58.5± 4.5)%,Particle size(247.7 ± 17.3) nm and zeta potential(33.5 ±3.9) mV. Transmission electron microscopy showed homogeneous spherical particles in the nanometer range. A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution. No ocular damages were observed in the susceptibility test on albino rabbits. The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers, and chitosanSLNs is a potential carrier for ophthalmic administration.
基金Supported by the National Natural Scientific Foundation of China(No.50472069)the Key Scientific Project from the Chinese Education Ministry(No.106100)
文摘Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. The physical stability of the nanoparticles was investigated by zeta potential measurement and they were shown to be quite stable. Fluorescence spectroscopy confirmed that the loaded position of BSA was on the interface between the inner aqueous phase and the solid lipid phase. Both Fourier-transform infrared spectroscopy and circular dichroism spectra indicate that BSA in the nanoparticles was not destroyed, but the secondary structure was disrupted slightly.
文摘Nanotechnology is a rapidly expanding discipline,and solid lipid nanoparticles(SLN)are at the forefront of this development.They offer various possible clinical and pharmaceutical research applications and numerous other fields.A quantitative review technique called bibliometric analysis uses statistics,data mining,and mathematics to find emerging trends in a particular academic topic.It is currently more widely utilized and is employed in many academic subjects.As a result,the current study looked through Scopus-indexed research documents on SLNs from 2012 to 2022 to assess the growth and expansion of this body of knowledge and predict its course in the future.The VOSviewer package and Scopus Analytics were used to conduct the bibliometric analysis.VOSviewer offers two distinct viewing modes:network and overlay visualization.A total of 3768 journal articles(n=3709)and conference papers(n=59)were extracted.The number of research documents published by 12,367 authors was steadily increasing annually.Gene therapy,development and detection methods,bioavailability,and controlled release have been important research subjects.Souto,E.B.,of the University of Porto in Portugal,is considered the most prolific and frequently cited scholar.Punjab University(India)is the top-publishing institution.India is the leading country in the number of publications and research collaborations.The International Journal of Pharmaceutics is the top source.The current results keep pace with global scientific efforts in nanotechnology and successfully integrate them into the pharmaceutical industry.
基金supported by Fundacao para a Ciência e a Tecnologia(FCT)(SFRH/136177/2018,Portugal)the Applied Molecular Biosciences Unit-UCIBIO which is fnanced by national funds from FCT(UIDP/04378/2020 and UIDB/04378/2020)。
文摘The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.
基金the project grants from National Natural Science Foundation of China(81703431 and 81673375)the Natural Science Fund Project of Guangdong Province(2016A030312013,China)。
文摘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 infuence 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 signifcantly 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 p H 7.4,while by electrostatic attraction in pH 6.0,and size-dependent adsorption was confrmed.This study provides a systematic insight to the understanding of protein corona formation of SLNs.
文摘In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size,zeta potential,drug entrapment efficiency,in vitro drug release,and stability.All parameters were found to be in an acceptable range.In vitro drug release was found to be 94.1674.78%after 24 h and was fitted to the Higuchi model with a very high correlation coefficient(R2¼0.9941).Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography.The brain/blood ratio at 0.5 h for HP-SLNs i.n.,HP sol.i.n.and HP sol.i.v.was 1.61,0.17 and 0.031,respectively,indicating direct nose-to-brain transport,bypassing the blood-brain barrier.The maximum concentration(Cmax)in brain achieved from i.n.administration of HP-SLNs(329.17720.89 ng/mL,Tmax 2 h)was significantly higher than that achieved after i.v.(76.9577.62 ng/mL,Tmax 1 h),and i.n.(90.1376.28 ng/mL,Tmax 2 h)administration of HP sol.The highest drug-targeting efficiency(2362.43%)and direct transport percentage(95.77%)was found with HP-SLNs as compared to the other formulations.Higher DTE(%)and DTP(%)suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.
基金Financial support to Anan Yaghmur for studies on development of drug nanocarriers based on cubosomes and hexosomes by the Danish Council for Independent Research|Technology and Production Sciences(references 1335-00150b and DFF-7017-00065,Denmark)。
文摘The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.
基金Natural Science Foundation of Tianjin(09TCYBTC13500)
文摘Objective To evaluate the difference of the pharmacokinetic(PK)and tissue distribution properties in mice administrated with lyophilized icariin stealth solid lipid nanoparticles(Ica-SSLN)modified by polyethylene glycol and icariin control solution(Ica-Sol).Meanwhile,to establish a sensitive,specific,and stable HPLC method for the determination of Ica in mice plasma and various tissues.Methods Ica-SSLN was prepared by high temperature melt-cool solidification method.Particle size and Zeta potentials were measured by a ZetaPlus.After iv administration of Ica-SSLN and Ica-Sol at a single dose of 7.46 mg/kg,the blood and tissues including brain,liver,spleen,lung, heart,and kidney were collected at different time points.The obtained concentration from HPLC analysis was statistically treated to determine the PK model and the relevant PK parameters using DAS1.0.Tissue distribution studies of Ica-SSLN were carried out in Kunming mice after iv administration and compared to Ica-Sol.Results The characteristic data showed that the mean particle size of Ica-SSLN was(50.03±0.90)nm,entrapment efficiency was(71.67±1.09)%,and the particles carried negative charge,Zeta potential was(?22.77±1.89)mV.The concentration-time profiles of Ica in mice after iv administrated with Ica-SSLN and Ica-Sol were shown to fit a two-compartment open model.Compared with Ica-Sol,the t1/2βof Ica-SSLN was prolonged by seven times and the AUC was increased by four times.The levels of Ica concentration in the kidney tissues were significantly increased. In addition,compared with Ica-Sol,the relative target efficiency to kidney tissue was 79%and the relative tissue exposure was 16.95.Conclusion It demonstrates that Ica-SSLN has selective targeting to kidney tissue and the kidney targeted Ica-SSLN seems to have significant advantages and good development value.
基金supported by the Natural Science Foundation of Anhui Province(Grant No.2008085QH362)Key Program of Anhui Educational Committee(Grant No.KJ2020ZD51)+2 种基金Translational Medicine Key Projects of Bengbu Medical College(Grant Nos.BYTM2019006 and BYTM 2019012)Scientific Research Innovation Team of Bengbu Medical College(Grant No.BYKC201910)512 Talents Development Project of Bengbu Medical College(Grant Nos.by51202302 and by51202309).
文摘Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal spontaneously.Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts.In this study,we developed an innovative bone engineering scaffold based on gelatin methacrylate(GelMA)hydrogel,obtained via a two-step procedure:first,solid lipid nanoparticles(SLNs)were loaded with resveratrol(Res),a drug that can promote osteogenic differentiation and bone formation;these particles were then encapsulated at different concentrations(0.01%,0.02%,0.04%and 0.08%)in GelMA to obtain the final Res-SLNs/GelMA scaffolds.The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone regeneration in rat cranial defects were evaluated using various characterization assays.Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs,with the ideally slow and steady release of Res;the optimal scaffold was 0.02 Res-SLNs/GelMA.Therefore,the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility,osteoconduction and osteoinduction,thereby showing potential for application in bone tissue engineering.
基金provided by a grant from Boston University,United States,Fundacao de Amparo à Pesquisa do Estado de Sao Paulo(FAPESP),Sao PauloConselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq),Brasília,Brazila scholarship from Coordena??o de Aperfeicoamento de Pessoal de Nível Superior-CAPES
文摘Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel (4 mg/kg) while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area (14%) and stenosis (22%) by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.
基金supported by the National Natural Science Foundation of China(Grant No.81222054 and 81302742)State Administration of Traditional Chinese Medicine(No.201307002)the Key Research Project of Department of Education of Sichuan(11ZA005)
文摘Background: Curcuminoids are promising cancer chemopreventive agents. Curcumin, demethoxycurcumin(DMC) and bisdemethoxycurcumin(BDMC) are the major bioactive curcuminoids in turmeric. However, comprehensive metabolic studies of these three curcuminoids are still limited.Objective: To identify the metabolites of curcumin, DMC and BDMC in rats after oral administration of solid lipid nanoparticles(SLNs).Methods: Male Sprague-Dawley rats(250 ± 20 g, body weight) were randomly divided into 4 groups(n=3), and were orally administered with curcumin-SLN, DMC-SLN, BDMC-SLN, or blank-SLN, respectively. Plasma samples(500 μL) via the angular vein were collected at 1, 2 and 4 h post dosing, and the urine and feces samples were collected at 0–12 h and 12–24 h post-intake. An HPLC-DAD-ESI-MSnmethod was developed to identify the metabolites. The structures of phase II metabolites were further confirmed by enzyme hydrolysis.Results: A total of 34 metabolites were identified in rats plasma, urine, and feces. Most of them were phase II metabolites, including glucuronide conjugates and sulfate conjugates. Among them, the glucuronide conjugates were the major metabolites in rats plasma. In the meanwhile, the three parent curcuminoids were detected in high amounts in the urine and feces samples.Conclusion: The possible metabolic pathways of curcuminoids in rats were proposed.
基金financial support from the National Natural Science Foundation of China (81673372, 81690263, 81361140344 and 81773911)the National Basic Research Program of China (2013CB 932502)+2 种基金the Opening Project of Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (Sichuan University, Chengdu, China)the Development Project of Shanghai Peak Disciplines–Integrated Medicine (No. 20150407)the Open Project Program of Key Lab of Smart Drug Delivery (Fudan University, Shanghai, China), Ministry of Education, China
文摘Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.