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
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
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
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
Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN...Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.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
The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacroli...The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate(Compritol~?ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion-and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.展开更多
An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters bet...An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.展开更多
In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which ca...In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.展开更多
To review the latest research development of the solid lipid nanoparticles(SLN) according to the recent relevant literatures.Each preparations of the SLN have advantages and disadvantages.Among the total preparations ...To review the latest research development of the solid lipid nanoparticles(SLN) according to the recent relevant literatures.Each preparations of the SLN have advantages and disadvantages.Among the total preparations of the SLN.the high pressure homogenization(HPH) and the microemulsion tech- nique are to praise highly.The drug incorporation and release profiles could be modified as adjustment of production parameters.The SLNis an excellent drug delivery system and has broad prospects in the phar- maceutical field.展开更多
Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its ...Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.展开更多
AIM:To investigate colorectal uptake of solid lipid nanoparticles(SLNs) in mice receiving different doses of 1,2-dimethylhydrazine(DMH) using magnetic resonance(MR) and laser-scanning confocal fluorescence microscope(...AIM:To investigate colorectal uptake of solid lipid nanoparticles(SLNs) in mice receiving different doses of 1,2-dimethylhydrazine(DMH) using magnetic resonance(MR) and laser-scanning confocal fluorescence microscope(LSCFM) imaging.METHODS:Eight mice were sacrificed in a pilot study to establish the experimental protocol and to visualize colorectal uptake of SLNs in normal mice.Gadopentetate dimeglumine and fluorescein isothiocyanate(FITC)-loaded SLN(Gd-FITC-SLN) enemas were performed on mice receiving DMH for 10 wk(group 1,n = 9) or 16 wk(group 2,n = 7) and FITC-SLN enema wasperformed on 4 DMH-treated mice(group 3).Pre-and post-enema MR examinations were made to visualize the air-inflated distal colorectum.Histological and LSCFM examinations were performed to verify colorectal malignancy and to track the distribution of SLNs.RESULTS:Homogeneous enhancement and dense fluorescence(FITC) deposition in colorectal wall were observed in normal mice and 1 DMH-treated mouse(group 1) on fluid attenuated inversion recovery(FLAIR) and LSCFM images,respectively.Heterogeneous mural enhancement was found in 6 mice(4 in group 1;2 in group 2).No visible mural enhancement was observed in the other mice.LSCFM imaging revealed linear fluorescence deposition along the colorectal mucosa in all groups.Nine intraluminal masses and one prolapsed mass were detected by MR imaging with different enhancement modes and pathologies.Interstitial FITC deposition was identified where obvious enhancement was observed in FLAIR images.Bladder imaging agent accumulations were observed in 11 of 16 DMH-treated mice of groups 1 and 2.CONCLUSION:There are significant differences in colorectal uptake and distribution of SLNs between normal and DMH-treated mice,which may provide a new mechanism of contrast for MR colonography.展开更多
Oleanolic acid-loaded solid lipid nanoparticles（OA-SLNs）were prepared by using an improved emulsion-solvent evaporation method.The size,zeta potential,encapsulation efficiency,and loading efficiency of OA-SLNs were...Oleanolic acid-loaded solid lipid nanoparticles（OA-SLNs）were prepared by using an improved emulsion-solvent evaporation method.The size,zeta potential,encapsulation efficiency,and loading efficiency of OA-SLNs were（104.5±11.7）nm, （-25.5±1.8）mV,（94.2±3.9）%,and（4.71±0.15）%,respectively.The morphology was illustrated by TEM as sphere stuffed particles.The XRD and DSC spectra confirmed that the OA molecules were dispersed uniformly into SLN matrixes.The results of in vitro release test suggested that OA was released slowly at a rate of 4.88%per hour from SLN preparation,which was consistent with the Zero-order Released Model.In addition,OA-SLNs were stable in artificial gastric juice and artificial intestinal juice.Together,our results provided new data for the potential application of OA-SLNs in oral administration.展开更多
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.
文摘Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.
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.
文摘The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate(Compritol~?ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion-and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.
基金Supported by the National Natural Science Foundation of China （No.20536020, No.20476033）, the China Distinguished Young Scientist Fund （No.20225620） and Guangdong Province Science Fund （No.04020121）.
文摘An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.
文摘In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.
文摘To review the latest research development of the solid lipid nanoparticles(SLN) according to the recent relevant literatures.Each preparations of the SLN have advantages and disadvantages.Among the total preparations of the SLN.the high pressure homogenization(HPH) and the microemulsion tech- nique are to praise highly.The drug incorporation and release profiles could be modified as adjustment of production parameters.The SLNis an excellent drug delivery system and has broad prospects in the phar- maceutical field.
基金Science and Technology Department of Henan province Fund Project(Grant No.144300510019)
文摘Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.
基金Supported by National Natural Science Foundation of China,No.30670610
文摘AIM:To investigate colorectal uptake of solid lipid nanoparticles(SLNs) in mice receiving different doses of 1,2-dimethylhydrazine(DMH) using magnetic resonance(MR) and laser-scanning confocal fluorescence microscope(LSCFM) imaging.METHODS:Eight mice were sacrificed in a pilot study to establish the experimental protocol and to visualize colorectal uptake of SLNs in normal mice.Gadopentetate dimeglumine and fluorescein isothiocyanate(FITC)-loaded SLN(Gd-FITC-SLN) enemas were performed on mice receiving DMH for 10 wk(group 1,n = 9) or 16 wk(group 2,n = 7) and FITC-SLN enema wasperformed on 4 DMH-treated mice(group 3).Pre-and post-enema MR examinations were made to visualize the air-inflated distal colorectum.Histological and LSCFM examinations were performed to verify colorectal malignancy and to track the distribution of SLNs.RESULTS:Homogeneous enhancement and dense fluorescence(FITC) deposition in colorectal wall were observed in normal mice and 1 DMH-treated mouse(group 1) on fluid attenuated inversion recovery(FLAIR) and LSCFM images,respectively.Heterogeneous mural enhancement was found in 6 mice(4 in group 1;2 in group 2).No visible mural enhancement was observed in the other mice.LSCFM imaging revealed linear fluorescence deposition along the colorectal mucosa in all groups.Nine intraluminal masses and one prolapsed mass were detected by MR imaging with different enhancement modes and pathologies.Interstitial FITC deposition was identified where obvious enhancement was observed in FLAIR images.Bladder imaging agent accumulations were observed in 11 of 16 DMH-treated mice of groups 1 and 2.CONCLUSION:There are significant differences in colorectal uptake and distribution of SLNs between normal and DMH-treated mice,which may provide a new mechanism of contrast for MR colonography.
基金National Basic Research Program of China(973 Program Grant No.2009CB930300)National Integrity Innovational Technology Platform of New Drug and Research and Development (Grant No.2009ZX09310-001).
文摘Oleanolic acid-loaded solid lipid nanoparticles（OA-SLNs）were prepared by using an improved emulsion-solvent evaporation method.The size,zeta potential,encapsulation efficiency,and loading efficiency of OA-SLNs were（104.5±11.7）nm, （-25.5±1.8）mV,（94.2±3.9）%,and（4.71±0.15）%,respectively.The morphology was illustrated by TEM as sphere stuffed particles.The XRD and DSC spectra confirmed that the OA molecules were dispersed uniformly into SLN matrixes.The results of in vitro release test suggested that OA was released slowly at a rate of 4.88%per hour from SLN preparation,which was consistent with the Zero-order Released Model.In addition,OA-SLNs were stable in artificial gastric juice and artificial intestinal juice.Together,our results provided new data for the potential application of OA-SLNs in oral administration.
