Vandana Soni

Transferrin coupled liposomes as drug delivery carriers for brain targeting of 5-florouracil

Diseases and disorders of the brain are extremely difficult to treat pharmacologically because most drugs are unable to pass across the blood–brain barriers. Complex multi-strand tight junctions between adjacent cerebral endothelial cells and between choroid plexus epithelial cells form a physical barrier and prevent the passage of water soluble drugs from the blood into the brain, whereas the inward passage of lipid soluble drugs is restricted by drug efflux pumps which act as a functional barrier. In the present work, a transferrin-coupled liposomal system for brain delivery of 5-florouracil has been investigated. 5-florouracil and 99mTc-DTPA bearing non-coupled liposomes were prepared by cast film method, which were coupled with the transferrin by incubating these liposomes with transferrin in the presence of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in saline phosphate buffer (pH 7.4). These liposomal systems were characterized for vesicle size, percent drug entrapment, and in vitro drug release. The size of the liposomes was increased on coupling with transferrin while percent drug entrapment reduced. The results of the in vitro release profile demonstrated that non-coupled liposomal formulation releases a comparatively higher percent (i.e. 74.8±3.21%) of drug than coupled liposomes. Results of in vivo study suggested a selective uptake of the transferrin-coupled liposomes from the brain capillary endothelial cells. In case of coupled liposomes, the level of radioactivity was 17-fold more as compared to the free radioactive agent and 13 times more with the non-coupled liposomes. Therefore, it could be concluded that using transferrin coupled liposomes the brain uptake of the drug could be enhanced.

Transferrin-conjugated liposomal system for improved delivery of 5-fluorouracil to brain

The objective of this study is to achieve the enhanced delivery of 5-fluorouracil to brain through transferrin-coupled liposomes. 5-Fluorouracil-loaded liposomes were prepared by cast film method and characterized for particle size, shape, percent encapsulation efficiency and in vitro drug release. Biodistribution studies were carried out with the help of radiolabelled 5-fluorouracil. 5-Fluorouracil was labelled with 99mTc-DTPA by oxidation–reduction method using stannous chloride and optimized for labelling parameters to get a high labelling efficiency. The in vitro stability was determined to check the efficiency of a system to find out the suitability of the radiolabelled system for in vivo studies. 99mTc-DTPA-labelled 5-fluorouracil bearing non-coupled and coupled liposomes were administered intravenously and biodistribution studies were performed. The distribution of 5-fluorouracil via non-coupled and coupled liposomes was determined in various organs, such as lungs, liver, kidneys, spleen and brain, by measuring the radioactivity using a gamma scintillation unit. The results of in vivo studies confirmed a selective uptake of the transferrin-coupled liposomes from the brain capillary endothelial cells. An average of 10-fold increase in the brain uptake of the drug was observed after the liposomal delivery of 5-fluorouracil, while the transferrin-coupled liposomes caused a 17-fold increase in the brain uptake of 5-fluorouracil. Therefore, it can be concluded that transferrin-coupled liposomes enhance the brain uptake of the drug, like 5-fluorouracil.

Surface engineered polymeric nanocarriers mediate the delivery of transferrin–methotrexate conjugates for an improved understanding of brain cancer

The objective of present study was to enhance permeation of bioactive molecules across blood brain barrier (BBB) through polysorbate 80 coated poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with methotrexate-transferrin (Tw-Mtx-Tf-NP) conjugates (Mtx-Tf). The easy trans-BBB migration of developed formulations through endocytosis, and inhibition of P-gp efflux pump present in brain were established by Pluronic F-68 and/or polysorbate 80 (Tween 80/Tw). The over-expression of transferrin (Tf) receptors on cancer cell surface allowed targeted and sustained delivery of Mtx-Tf conjugated to brain cancer cells by receptor mediated endocytosis. The developed formulations showed improved penetration in comparison to non-targeting experimental NP controls. The transportation potential and bio-distribution studies of such nanosized polymeric carriers showing successful migration and trans-BBB passage was carried out by administering FITC labeled drug loaded NPs to albino rats through intravenous route. We have validated anti-tumor efficiency of newly formulated and drug loaded NPs compared to controls in experimentally induced tumor-harboring rat model. The present study suggests greater compatibility, less organ toxicity and higher anti-tumor activity of developed formulations due to their targeting and sustained delivery potential in cancer therapeutic interventions. In conclusion, our findings of targeted and sustained drug delivery potential of NPs for are corroborated with in vitro and in vivo evidence, and formulated novel delivery vehicle shows its value in developing new tools for treating brain cancer.

Lactoferrin-appended solid lipid nanoparticles of paclitaxel for effective management of bronchogenic carcinoma

Abstract Lung cancer is a dreadful disease which claims to be more life threatening as compared to total sum up of colon, prostate and breast cancers. Thus, there is an urgent need to develop an effective delivery approach for its management. Paclitaxel (PTX) is one of the well-known choice as antineoplasitic agent used for the treatment of different types of human cancers such as non-small-cell lung, head and neck cancers, leukemia, breast, ovarian and melanoma. Lactoferrin (Lf), a “multifunctional protein” is crucial for natural immunity which is secreted by exocrine glands. Lf receptors are expressed on the apical surface on bronchial epithelial cells. These over-expressed LF receptors can be utilized for the transportation of Lf-conjugated drug or nanocarrier devices. The present study was aimed to develop PTX-loaded Lf-coupled solid lipid nanoparticles (SLNs) for the treatment of lung cancer. PTX-loaded SLNs were prepared, characterized and then coupled with Lf using carbodiimide chemistry. The formulations were characterized by transmission electron microscopy, particle size, polydispersity index and zeta potential, whereas Lf conjugation was confirmed by FT-IR and 1H NMR and efficiency of prepared system was evaluated by in vitro, ex vivo and in vivo evaluations. The ex vivo cytotoxicity studies on human bronchial epithelial cell lines, BEAS-2B, revealed superior anticancer activity of Lf-coupled SLNs than plain SLNs and free PTX. In vivo biodistribution studies showed higher concentrations of PTX accumulated in lungs via Lf-coupled SLNs than plain SLNs and free PTX. These studies suggested that Lf-coupled PTX-loaded SLNs could be used as potential targeting carrier for delivering anticancer drug to the lungs with the minimal side effects.

Assessment of lactoferrin-conjugated solid lipid nanoparticles for efficient targeting to the lung

AbstractThe aim of the presentn study was to develop a target oriented drug delivery system for the lungs. Lactoferrin (Lf)-coupled solid lipid nanoparticles (SLNs) bearing rifampicin was prepared by a solvent injection method. The prepared nanoparticles were characterized for shape, particle size, polydispersity and percentage drug entrapment. An optimized formulation was then studied for its in vivo performance in animals and to determine its targeting efficiency. It was observed that, upon coupling with Lf, the size of SLNs increased while the percent entrapment efficiency decreases. In in vitro release, determined by a dialysis technique, analysis showed that uncoupled SLNs exhibited higher drug release as compared to coupled SLNs. An in vivo biodistribution study shows 47.7xa0±0.4 drug uptakes by the lungs, which was 3.05 times higher in comparison to uncoupled SLNs. These biodistribution studies are further supported by the fluorescence study that revealed enhanced uptake of Lf-coupled SLNs in the lung. From the presented results, it can be concluded that Lf-coupled SLNs enhanced drug uptake in the lung. Moreover, lactoferrin is an efficient molecule that can be used for targeting active agents directly to the lung.

Pulsatile Insulin Delivery Through the Ocular Route

A liposomal system bearing insulin was developed for controlled and prolonged delivery of drug through the ocular route. The systems were prepared by the cast film method using various lipids in different weight ratios. These products were characterized by their physical attributes, viz., shape, size, charge, and encapsulation efficiency. The effect of temperature on the formulation was also studied by measuring the shape and drug content. An in vitro drug release study was carried out using a franz diffusion cell and artificial tear solution as diffusion medium. An in vivo experiment was conducted on rabbits by periodic monitoring the blood glucose level after the instillation of the product in the animals eye. The results indicate the potentiality of the liposomal system for controlled delivery of insulin for prolonged periods of time. Thus, pulsatile delivery of insulin can be achieved using temperature-sensitive liposomal formulation.

Nanostructure lipid carriers: A modish contrivance to overcome the ultraviolet effects

Abstract Protection of the skin from the ultraviolet radiation is the prime concern of society. An increase in the adverse effects by ultraviolet (UV) radiation on the skin promoted cosmetic formulators to work in the area of UV blockers and their effective means of delivery. Nanostructured lipid carriers (NLCs) is a modern and successful lipid carrier system in the cosmetic world associated with various advantages i.e., stability, effective drug loading capacity etc. NLCs also permits to load 70% of UV blockers which are sufficient to obtain recommended Sun Protection Factor (SPF) which makes them suitable delivery systems for topical application of the UV blockers.

Ascorbic acid tethered polymeric nanoparticles enable efficient brain delivery of galantamine: An in vitro - in vivo study

The aim of this work was to enhance the transportation of the galantamine to the brain via ascorbic acid grafted PLGA-b-PEG nanoparticles (NPs) using SVCT2 transporters of choroid plexus. PLGA-b-PEG copolymer was synthesized and characterized by 1H NMR, gel permeation chromatography, and differential scanning calorimetry. PLGA-b-PEG-NH2 and PLGA-b-mPEG NPs were prepared by nanoprecipitation method. PLGA-b-PEG NPs with desirable size, polydispersity, and drug loading were used for the conjugation with ascorbic acid (PLGA-b-PEG-Asc) to facilitate SVCT2 mediated transportation of the same into the brain. The surface functionalization of NPs with ascorbic acid significantly increased cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells as compared to plain PLGA and PLGA-b-mPEG NPs. In vivo pharmacodynamic efficacy was evaluated using Morris Water Maze Test, Radial Arm Maze Test and AChE activity in scopolamine induced amnetic rats. In vivo pharmacodynamic studies demonstrated significantly higher therapeutic and sustained action by drug loaded PLGA-b-PEG-Asc NPs than free drugs and drug loaded plain PLGA as well as PLGA-b-mPEG NPs. Additionally, PLGA-b-PEG-Asc NPs resulted in significantly higher biodistribution of the drug to the brain than other formulations. Hence, the results suggested that targeting of bioactives to the brain by ascorbic acid grafted PLGA-b-PEG NPs is a promising approach.

Therapeutic challenges in ocular delivery of lipid based emulsion

Abstract In the last decade, lipid based emulsions (LEs) have emerged as a novel tool in ophthalmic drug delivery from the aspect of improved bioavailability (BA). Recent research is focuses on two main approaches for BA improvement i.e., by enhancing the corneal permeability and increasing the retention time of drug on the ocular surface. The LEs have great potential to delivery hydrophobic drug because drug molecules get dissolve in oil globule and main advantage associated are reduced toxic effect and improved self-life of drug molecule. Ophthalmic drug delivery is always an interesting and challenging task for the pharmacologists and formulation scientists due to the unique structure of eye. Development of drug delivery system and its delivery to target receptor of the eye is very difficult for scientists due to the strong defense mechanism of eye. In this review, the focus is to explore key concepts of ophthalmic drug delivery with emphasis on the defense mechanisms, design considerations, and safety assessment of LEs for the ocular drug delivery.