Lactoferrin-Conjugated Dendritic Nanoconstructs for Lung Targeting of Methotrexate

Kurmi, Balak Das; Gajbhiye, Virendra; Kayat, Jitendra; Jain, Narendra Kumar

doi:10.1002/jps.22469

Cited by 56 publications

(17 citation statements)

References 21 publications

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“…30 Dendritic polymers have recently been shown to improve the delivery of doxorubicin and other cytotoxic drugs to solid tumors and to reduce their accumulation in noncancerous tissues. 31 Dendrimers have also been well proven as a tool in the solubilization of poorly soluble drugs, and poly(amidoamine) dendrimers and other polymeric dendrimers have been applied to flurbiprofen, 32 methotrexate, 33,34 and piroxicam 35 for solubilization and targeted delivery. In particular, lactoferrin-conjugated dendritic nanocomposite exhibited an enhanced residence time in the systemic circulation and high lung delivery, possibly leading to reduced dosing frequency as well as nominal dose.…”

Section: Dendrimersmentioning

confidence: 99%

Nanodrugs: pharmacokinetics and safety

Onoue¹,

Yamada²,

Chan³

2014

IJN

312

153

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To date, various nanodrug systems have been developed for different routes of administration, which include dendrimers, nanocrystals, emulsions, liposomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles. Nanodrug systems have been employed to improve the efficacy, safety, physicochemical properties, and pharmacokinetic/pharmacodynamic profile of pharmaceutical substances. In particular, functionalized nanodrug systems can offer enhanced bioavailability of orally taken drugs, prolonged half-life of injected drugs (by reducing immunogenicity), and targeted delivery to specific tissues. Thus, nanodrug systems might lower the frequency of administration while providing maximized pharmacological effects and minimized systemic side effects, possibly leading to better therapeutic compliance and clinical outcomes. In spite of these attractive pharmacokinetic advantages, recent attention has been drawn to the toxic potential of nanodrugs since they often exhibit in vitro and in vivo cytotoxicity, oxidative stress, inflammation, and genotoxicity. A better understanding of the pharmacokinetic and safety characteristics of nanodrugs and the limitations of each delivery option is necessary for the further development of efficacious nanodrugs with high therapeutic potential and a wide safety margin. This review highlights the recent progress in nanodrug system development, with a focus on the pharmacokinetic advantages and safety challenges.

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Section: Dendrimersmentioning

confidence: 99%

Nanodrugs: pharmacokinetics and safety

Onoue¹,

Yamada²,

Chan³

2014

IJN

312

153

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“…The dose administered to rat was 25 mg/kg body weight. The surgical procedures were followed as described elsewhere (Kurmi et al, 2011). Plain PTX, PTX-loaded SLNs and PTX-loaded Lf-coupled SLNs formulations were administered to the each rat of first, second and third group, respectively through the tail vein.…”

Section: In Vivo Blood Level and Biodistribution Studiesmentioning

confidence: 99%

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

2014

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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.

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“…Novel properties of dendrimers subjected them for immense exploration among the researchers, which has led to their possible use in different pharmaceutical field like drug delivery [100][101][102][103], gene delivery [104][105][106][107], solubility enhancement [108], transfection [109] etc. Brain delivery of bioactive molecule for different brain diseases via dendrimers is very promising emerging field which has shown some very exiting results for treatment of these diseases.…”

Section: Treatment Strategies For Brain Diseases Using Dendrimersmentioning

confidence: 99%

Targeted Brain Delivery of Bioactive Molecules Using Nanocarriers

Kr¹,

Gajbhiye²,

Soni³

2015

J Bioequiv Availab

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Delivery of the bioactives to the brain is the utmost challenging task to cope with brain diseases. Brain is protected with blood brain barrier, blood-CSF barrier and efflux systems, which controls the entry of body as well as foreign compounds to access the brain cells. Only nutrients, which are essential for normal metabolism, can enter into the brain. In the shadow of this fact new strategies are being investigated to facilitate the entry of administered therapeutic compound into the brain. Active targeting is a evolving approach, which uses ligand and suitable carrier for the site-specific delivery and is being recently achieved by the use of nanocarriers. These nanocarriers are nanosized systems, which act as a cargo for the encapsulated drugs. At the same time, endo-or exogenous ligand can be attached to these nanocarriers to recognize specific receptors on brain capillary endothelium leading to delivery of drug in the vicinity of brain cells. Their potential is under immense investigation to increase the therapeutics outcome in the treatment of brain related problems. This review deals with the recent advances in nanocarriers based novel strategies for effective brain specific delivery.

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Lactoferrin-Conjugated Dendritic Nanoconstructs for Lung Targeting of Methotrexate

Cited by 56 publications

References 21 publications

Nanodrugs: pharmacokinetics and safety

Nanodrugs: pharmacokinetics and safety

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

Targeted Brain Delivery of Bioactive Molecules Using Nanocarriers

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