scholarly journals Brain targeted delivery of rapamycin using transferrin decorated nanostructured lipid carriers

Bioimpacts ◽  
2021 ◽  
Author(s):  
Fatemeh Khonsari ◽  
Mostafa Heydari ◽  
Rassoul Dinarvand ◽  
Mohammad Sharifzadeh ◽  
Fatemeh Atyabi
Keyword(s):  
Targeted Delivery ◽  
Water Solubility ◽  
In Vitro Study ◽  
Entrapment Efficiency ◽  
Immunosuppressive Effect ◽  
Brain Diseases ◽  
Therapeutic Effects ◽  
Nanostructured Lipid Carrier

Introduction: Recent studies showed that rapamycin, as a mammalian target of rapamycin (mTOR) inhibitor, could have beneficial therapeutic effects for the central nervous system (CNS) related diseases. However, the immunosuppressive effect of rapamycin as an adverse effect, the low water solubility, and the rapid in vivo degradation along with the blood-brain barrier-related challenges restricted the clinical use of this drug for brain diseases. To overcome these drawbacks, a transferrin (Tf) decorated nanostructured lipid carrier (NLC) containing rapamycin was designed and developed. Methods: Rapamycin-loaded cationic and bare NLCs were prepared using solvent diffusion and sonication method and well characterized. The optimum cationic NLCs were physically decorated with Tf. For in vitro study, the MTT assay and intracellular uptake of nanoparticles on U-87 MG glioblastoma cells were assessed. The animal biodistribution of nanoparticles was evaluated by fluorescent optical imaging. Finally, the in vivo effect of NLCs on the immune system was also studied. Results: Spherical NLCs with small particle sizes ranging from 120 to 150 nm and high entrapment efficiency of more than 90%, showed ≥80% cell viability. More importantly, Tf-decorated NLCs in comparison with bare NLCs, showed a significantly higher cellular uptake (97% vs 60%) after 2 hours incubation and further an appropriate brain accumulation with lower uptake in untargeted tissue in mice. Surprisingly, rapamycin-loaded NLCs exhibited no immunosuppressive effect. Conclusion: Our findings proposed that the designed Tf-decorated NLCs could be considered as a safe and efficient carrier for targeted brain delivery of rapamycin which may have an important value in the clinic for the treatment of neurological disorders.

DEVELOPMENT, CHARACTERIZATION AND BRAIN DISTRIBUTION STUDIES OF NANOSTRUCTURED LIPID CARRIER CONTAINING SAQUINAVIR MESYLATE FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (09) ◽  
pp. 38-47
Author(s):  
H. S. Mahajan ◽  
◽  
M. I. Patel
Keyword(s):  
Adverse Effect ◽  
Targeted Delivery ◽  
Entrapment Efficiency ◽  
Nasal Administration ◽  
Nanostructured Lipid Carrier ◽  
Brain Distribution ◽  
Scanning Calorimetry ◽  
Distribution Studies

The aim of the present study was to formulate saquinavir mesylate loaded nanostructured lipid carriers (SQVM-NLC) and evaluate its brain distribution after nasal administration. NLCs reveal some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. SQVM-NLCs were prepared by hot high pressure homogenization and subsequent stabilization by lyophilization. QVM- NLC developed showed a particle with the size of 124.4 nm, polydispersity index of 0.267, entrapment efficiency of 73% and the zeta potential of -24.9 mV. The results from Scanning Electron Microscopy (SEM), powder X-ray diffraction (XRD)and differential scanning calorimetry (DSC) demonstrated that SQVM was present in NLC in an encapsulated molecule form. Mucosal toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVMloaded NLC. SQVM-NLC showed slower release compared with saquinavir mesylate suspension in vitro. In vivo brain distribution studies demonstrated desired drug concentration in brain after intra nasal administration of SQVM-NLC than PDS. The results of the study also suggest that SQVM-NLC could be a promising drug delivery system for antiretroviral therapy.

scholarly journals Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1059
Author(s):  
Saif Ahmad Khan ◽  
Saleha Rehman ◽  
Bushra Nabi ◽  
Ashif Iqubal ◽  
Nida Nehal ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Fold Increase ◽  
Pharmacokinetic Studies ◽  
Nanostructured Lipid Carrier ◽  
Brain Delivery ◽  
The Brain

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

Preparation and Characterization of PEGylated Iron Oxide-Gold Nanoparticles for Delivery of Sulforaphane and Curcumin

Drug Research ◽  
2017 ◽  
Vol 67 (12) ◽  
pp. 698-704 ◽  
Author(s):  
Hossein Danafar ◽  
Ali Sharafi ◽  
Sonia Askarlou ◽  
Hamidreza Manjili
Keyword(s):  
Cell Line ◽  
Water Solubility ◽  
Drug Loading ◽  
In Vitro Study ◽  
Entrapment Efficiency ◽  
Breast Adenocarcinoma ◽  
Therapeutic Effects ◽  
Loading Capacity ◽  
Au Nps

AbstractNatural products have been used for the treatment of various diseases such as cancer. Curcumin (CUR) and sulforaphane (SF) have anti-cancer effects, but their application is restricted because of their low water solubility and poor oral bioavailability. To improve the bioavailability and solubility of SF and CUR, we performed an advanced delivery of SF and CUR with PEGylated gold coated Fe3O4 magnetic nanoparticles (PEGylated Fe3O4@Au NPs) to endorse SF and CUR maintenance as an effective and promising antitumor drugs. The structure of the synthesized nanocarrieris evaluated by, transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). The results revealed that the size of NPs was 20 nm. They were mono-dispersed in water, with high drug-loading capacity and stability. CUR and SF were encapsulated into NPs with loading capacity of 16.32±0.023% and 15.74±0.015% and entrapment efficiency of 74.57±0.14% and 72.20±0.18% respectively. The in-vitro study of SF and CUR loaded PEGylated Fe3O4@Au NPs on human breast adenocarcinoma cell line (SK-BR-3) confirmed that cytotoxicity of SF and CUR can enhance when they are loaded on PEGylated Fe3O4@Au NPs in comparison to Free SF and void CUR. The results of flow cytometry and real-time PCR shown that nano-carriers can increase therapeutic effects of SF and CUR by apoptosis and necrosis induction as well as inhibiting of migration in SK-BR-3 cell line.

Development and Characterization of a Clobetasol Propionate Nanostructured Lipid Carrier-based Gel for the Treatment of Plaque Psoriasis

2020 ◽  
Vol 13 ◽  
Author(s):  
Ankita Dadwal ◽  
Neeraj Mishra ◽  
Raj Kumar Narang
Keyword(s):  
Skin Permeation ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Homogenization Method ◽  
Clobetasol Propionate ◽  
In Vivo Studies ◽  
Nanostructured Lipid Carrier ◽  
Safe Delivery

Background: Psoriasis is an autoimmune disease of the skin with lapsing episodes of hyperkeratosis, irritation, and inflammation. Numerous traditional and novel drug delivery systems have been used for better penetration through psoriatic barrier cells and also for retention in the skin. As there is no effective remedy for better penetration and retention is there because of the absence of an ideal carrier for effective and safe delivery of antipsoriatic drugs. Objectives: The main objective of this project is to develop Squalene integrated NLC based carbopol 940 gel to create a local drug depot in skin for improved efficacy against psoriasis. Methods: Homogenization method is used for the formulation of Nanostructured Lipid Carrier and were characterized on the basis of size, entrapment efficiency, polydispersity index (PDI), viscosity, spreadability, DSC, zeta potential, % in vitro release, in vitro skin permeation and retention studies, physical storage stability studies and in vivo studies can use other alternative models for induction of psoriasis by severe redness, swelling macroscopically and microvascular dilation edema lasting for 10 days. Further histopathology study was done to basses of changes in the skin. Conclusion: The optimized formulation of nanostructured lipid carrier-based gel has shown significant sustained release of clobetasol propionate. Further, this formulation has also shown retention in skin because of squalene as it is sebum derived lipid show affinity towards the sebaceous gland.

Chemotherapeutic potential of L-carnosine from stimuli-responsive magnetic nanoparticles against breast cancer model

Nanomedicine ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. 891-911
Author(s):  
Ragwa M Farid ◽  
Passent M E Gaafar ◽  
Heba A Hazzah ◽  
Maged W Helmy ◽  
Ossama Y Abdallah
Keyword(s):  
Magnetic Nanoparticles ◽  
Targeted Delivery ◽  
Physicochemical Characterization ◽  
Tumor Model ◽  
Entrapment Efficiency ◽  
In Vitro Cytotoxicity ◽  
Scanning Calorimetry ◽  
Chemotherapeutic Activity

Aim: L-carnosine-coated magnetic nanoparticles (CCMNPs) were developed to enhance chemotherapeutic activity of carnosine-dipeptide. Materials & methods: Surface grafting of MNPs with carnosine was contended by differential scanning calorimetry, infrared spectroscopy and x-ray diffraction. Physicochemical characterization and in vitro cytotoxicity on MCF-7 cell line was carried out. In vivo chemotherapeutic activity and toxicity was assessed by an Ehrlich Ascites tumor model. Results: CCMNPs possessed monodispersed size (120 nm), ζ (-27.3 mV), magnetization (51.52 emu/g) and entrapment efficiency (88.3%) with sustained release rate. CCMNPs showed 2.3-folds lower IC50 values compared with carnosine solution after 48 h. Targeted CCMNPs were specifically accumulated in tumor showing significant reduction in tumor size with no systemic toxicity. Significant reduction in VEGF and cyclin D1 levels were observed. Conclusion: The developed system endowed with responsiveness to an external stimulus can represent a promising magnetically targeted delivery system for carnosine site specific delivery.

scholarly journals CUR-CA-THIONE: A NOVEL CURCUMIN CONCOCTION WITH ENHANCED WATER SOLUBILITY AND BRAIN BIO-AVAILABILITY

2016 ◽  
Vol 8 (12) ◽  
pp. 265 ◽  
Author(s):  
Devang Y. Shelat ◽  
Sanjeev R Acharya
Keyword(s):  
Wistar Rats ◽  
Water Solubility ◽  
Release Kinetics ◽  
Entrapment Efficiency ◽  
Systemic Circulation ◽  
Oral Route ◽  
Male Wistar Rats ◽  
Dialysis Bag

<p><strong>Objective: </strong>Curcumin, is widely studied as a potential drug in treating various disorders but lacks applicability due to poor water solubility and tissue bioavailability. The main objective of the study was to develop a formulation of curcumin that has enhanced water solubility and brain bioavailability.</p><p><strong>Methods: </strong>A curcumin concoction was prepared using solvent evaporation technique taking casein and glutathione as vectors. Various process parameters were identified namely time, temperature, pH and vector while formulation parameters included drug entrapment, anti-oxidant activity, and water solubility. The concoctions were evaluated for <em>in vitro</em> release kinetics at three pH i.e. 1.2, 4.5 and 6.2 at six-time intervals i.e. 10, 20, 30, 40, 60, 120 min using dialysis bag membrane. The same kinetics was further validated using same time points with wistar rats and giving concoction at a single dose of 2 g/kg via the oral route.</p><p><strong>Results: </strong>A concoction i.e. CUR-CA-THIONE having significant entrapment efficiency (77.83%, 97.75%, 90.19%), water solubility (40, 350 and 45 times than normal curcumin) and DPPH activity (IC<sub>50</sub>: 28.91, 25.07 and 27.89) was evaluated in concoctions CUR-CA-THIONE-T.1, CUR-CA-THIONE-T.2 and CUR-CA-THIONE-T.3 respectively. These formulations were then carried out for <em>in vitro</em> release profile at different pH with average release obtained between 20-30 min. <em>In vivo</em> kinetics was studied by isolating tissues like brain, liver, lung, kidney and spleen in male wistar rats and maximum brain bioavailability was observed for CUR-CA-THIONE-T.3 at 30 min with 75 ng/g of brain tissue.</p><p><strong>Conclusion: </strong>The experiment helps in concluding that CUR-CA-THIONE has improved its water solubility and is able to by-pass systemic circulation to targeted activity.</p>

scholarly journals Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1767
Author(s):  
Abdullah Saad Abdullah ◽  
Ibrahim El Tantawy El Sayed ◽  
Abdel Moneim A. El-Torgoman ◽  
Noweir Ahmad Alghamdi ◽  
Sami Ullah ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Hepatic Fibrosis ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Serum Samples ◽  
Hepatic Expression

Background: The main obstacles of silymarin (SIL) application in liver diseases are its low bioavailability, elevated metabolism, rapid excretion in bile and urine, and inefficient intestinal resorption. The study aimed to synthesize and characterize silymarin-conjugated gold nanoparticles (SGNPs) formulation to improve SIL bioavailability and release for potentiating its antifibrotic action. Methods: Both SGNPs and gold nanoparticles (GNPs) were prepared and characterized using standard characterization techniques. The improved formulation was assessed for in vitro drug release study and in vivo study on rats using CCl4 induced hepatic fibrosis model. SIL, SGNPs, and GNPs were administered by oral gavage daily for 30 days. At the end of the study, rats underwent anesthesia and were sacrificed, serum samples were collected for biochemical analysis. Liver tissues were collected to measure the genes and microRNAs (miRNAs) expressions. Also, histopathological and immunohistochemistry (IHC) examinations of hepatic tissues supported these results. Results: The successful formation and conjugation of SGNPs were confirmed by measurements methods. The synthesized nanohybrid SGNPs showed significant antifibrotic therapeutic action against CCl4-induced hepatic damage in rats, and preserved normal body weight, liver weight, liver index values, retained normal hepatic functions, lowered inflammatory markers, declined lipid peroxidation, and activated the antioxidant pathway nuclear factor erythroid-2-related factor 2 (NRF2). The antifibrotic activities of SGNPs mediated through enhancing the hepatic expression of the protective miRNAs; miR-22, miR-29c, and miR-219a which results in suppressed expression of the main fibrosis mediators; TGFβR1, COL3A1, and TGFβR2, respectively. The histopathology and IHC analysis confirmed the anti-fibrotic effects of SGNPs. Conclusions: The successful synthesis of SGNPs with sizes ranging from 16 up to 20 nm and entrapment efficiency and loading capacity 96% and 38.69%, respectively. In vivo studies revealed that the obtained nano-formulation of SIL boosted its anti-fibrotic effects.

scholarly journals Optimization of Hyaluronate-Based Liposomes to Augment the Oral Delivery and the Bioavailability of Berberine

Materials ◽  
2021 ◽  
Vol 14 (19) ◽  
pp. 5759
Author(s):  
Hussam I. Kutbi ◽  
Hani Z. Asfour ◽  
Ahmed K. Kammoun ◽  
Alaa Sirwi ◽  
Simona Cavalu ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Water Solubility ◽  
Physical Stability ◽  
Entrapment Efficiency ◽  
Structural Features ◽  
Transmission Electron ◽  
Mean Size ◽  
Therapeutic Activities

Various perspectives had been utilized to enhance the poor intestinal permeability and bioavailability of drugs with low water solubility. Berberine (Brb) is a unique molecule that possesses multiple therapeutic activities such as antimicrobial, anti-inflammatory, antioxidant and anti-hyperglycemic effects. To improve Brb permeability and bioavailability, this study presents a newly developed formulation, namely Brb hyaluronate-based liposomes, prepared by using film hydration method and characterized by dynamic light scattering measurements, entrapment efficiency percentage (EE%), transmission electron microscope (TEM), in vitro drug release and physical stability. The bioavailability of the selected formulations was assessed in vivo after oral administration to rats. The results revealed an enhanced effect of hyaluronic acid on the entrapment efficiency, reaching 78.1 ± 0.1% with mean size 520.7 ± 19.9 nm. Sustained release of Brb was recorded up to 24 h in comparison to Brb solution. Physical stability was maintained for three months at refrigeration temperature. Results of pharmacokinetics studies indicated the potential of the liposomal formulation to increase the oral bioavailability of Brb and to accelerate its entry into the bloodstream. The obtained results are accredited to the lipophilic nature of the prepared system, resembling the structural features of bio-membrane, in addition to their small size that enhances intestinal penetration.

Preparation and In Vivo Characterization of Niosomal Carriers of the Antidiabetic Drug Repaglinide

2015 ◽  
Vol 8 (1) ◽  
pp. 2756-2767 ◽  
Author(s):  
Shrishti Namdev ◽  
Kishore Gujar ◽  
Satish Mandlik ◽  
Preeti Jamkar
Keyword(s):  
Particle Size ◽  
Factorial Design ◽  
Spherical Shape ◽  
Entrapment Efficiency ◽  
Therapeutic Effects ◽  
Drug Release Profile ◽  
Independent Variables ◽  
Span 60

The objective of this study is to prepare and characterise repaglinide niosomes using the Factorial Design strategy.Repaglinide is a potent second-generation oral hypoglycemic agent and has short half-life of 1 hour and oral bioavailability of 50%. Preparing Niosomal drugdelivery of repaglinide may increase its bioavailability which would lead to better therapeutic effects, reduce the frequency of dosing from twice a day to once a day and decrease side effects. The preliminary study was carried out for selection of surfactant and method of preparation based on least particle size and highest entrapment efficiency. For niosome preparation, organic solvent injection method was selected and span 60, cholesterol were selected as variable. A32 factorial design was used to optimize the effect of amounts of span 60(X1) and cholesterol (X2) which were the independent variables. Particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Relation between the dependent and independent variables were drawn out from the mathematical equations and response surface plots.Statistical analysis was performed using ANOVA which was found to be significant and quadratic equation was obtained by MLRA. The particle size was found to be in range of 144-497 nm and entrapment efficiency between 54-88%. Scanning electron microscopy indicated the spherical shape of the niosomes and formation of vesicle. Zeta potential analysis showed negatively charged surface with value of-36.7 mV. In vitro drug release profile showed that drug released fast initially followed by a slow release. In vivo pharmacokinetic study revealed that the niosomal preparation showed significant decrease in blood glucose level when compared to free repaglinide. The developed niosomal system also has potential of maintaining therapeutic level of RPG for longer period of time.Thus,the niosomes could be promising carriers for delivery ofrepaglinide with increased 

scholarly journals Development and Evaluation of 1′-Acetoxychavicol Acetate (ACA)-Loaded Nanostructured Lipid Carriers for Prostate Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 439
Author(s):  
Bavani Subramaniam ◽  
Norhafiza M. Arshad ◽  
Sharan Malagobadan ◽  
Misni Misran ◽  
Shaik Nyamathulla ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Chemical Properties ◽  
Tumor Model ◽  
Homogenization Method ◽  
Nanostructured Lipid Carrier ◽  
Animal Tumor

1′-acetoxychavicol acetate (ACA) extracted from the rhizomes of Alpinia conchigera Griff (Zingiberaceae) has been shown to deregulate the NF-ĸB signaling pathway and induce apoptosis-mediated cell death in many cancer types. However, ACA is a hydrophobic ester, with poor solubility in an aqueous medium, limited bioavailability, and nonspecific targeting in vivo. To address these problems, ACA was encapsulated in a nanostructured lipid carrier (NLC) anchored with plerixafor octahydrochloride (AMD3100) to promote targeted delivery towards C-X-C chemokine receptor type 4 (CXCR4)-expressing prostate cancer cells. The NLC was prepared using the melt and high sheer homogenization method, and it exhibited ideal physico-chemical properties, successful encapsulation and modification, and sustained rate of drug release. Furthermore, it demonstrated time-based and improved cellular uptake, and improved cytotoxic and anti-metastatic properties on PC-3 cells in vitro. Additionally, the in vivo animal tumor model revealed significant anti-tumor efficacy and reduction in pro-tumorigenic markers in comparison to the placebo, without affecting the weight and physiological states of the nude mice. Overall, ACA-loaded NLC with AMD3100 surface modification was successfully prepared with evidence of substantial anti-cancer efficacy. These results suggest the potential use of AMD3100-modified NLCs as a targeting carrier for cytotoxic drugs towards CXCR4-expressing cancer cells.

Sign in / Sign up

Export Citation Format

Share Document