Drug targeting to arthritic region via folic acid appended surface-engineered multi-walled carbon nanotubes.

This study was aimed at developing and investigating folate anchored carbon nanotubes for targeting an anti-arthritic drug, Methotrexate (MTX) to inflammatory arthritic region. The folic acid (FA) was conjugated to amidated multi-walled carbon nanotubes (MWCNTs) and confirmed by Fourier transform infrared (FTIR), (1)H NMR spectroscopy and X-ray diffraction analysis. The MTX was loaded into the pristine and functionalized-MWCNTs and extensively characterized in vitro and in vivo studies. The drug entrapment efficiency was found high in folate conjugated MWCNTs. In vitro drug release in PBS (pH 7.4) from pristine MWCNTs and folate conjugated MWCNTs formulation was found to be 66.35 ± 2.3 and 56.88 ± 1.9% in 24 h, respectively. Folate conjugated MWCNTs significantly increased (p < 0.005) the percentage inhibition of arthritis, biological half-life and volume of distribution of MTX as compared to MTX-loaded naked MWCNTs as well as free MTX. In in vivo biodistribution studies, MTX was found to be significantly higher (p < 0.005) in arthritic joints from folate functionalized MWCNTs as compared to free drug as well as drug-loaded naked MWCNTs. The present outcomes highlights the propensity of drug-loaded functionalized MWCNTs to alter the pharmacokinetics as well as sustained and targeted drug delivery system as well.

Lactoferrin-conjugated dendritic nanoconstructs for lung targeting of methotrexate.

The present investigation was aimed at developing and exploring the potential of lactoferrin (Lf)-conjugated dendritic nanocomposite for lung targeting of methotrexate (MTX). The 5.0 G poly(propylene imine) (PPI) dendrimer and Lf-conjugated 5.0 G PPI dendrimer were synthesized and characterized by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and transmission electron microscopy. The entrapment efficiency, in vitro release, and hemolytic toxicity were assessed. Pharmacokinetic and organ distribution studies were carried out to evaluate in vivo targeting potential of developed system. The pharmacokinetic studies showed that elimination half-life of MTX-loaded plain PPI dendrimer (10.41 ± 2.12 h, p < 0.05) and MTX-loaded Lf-conjugated PPI dendrimer (12.23 ± 1.53 h, p < 0.01) was significantly higher than the free drug (5.85 ± 1.19 h). Organ distribution assessment of different formulations displayed significant (p <0.05) higher accumulation of drug in lungs by MTX-Lf-PPI (1329 ± 26.7 ng/g of tissue) as compared with MTX-PPI (721 ± 23.4 ng/g of tissue) and free MTX (575 ± 19.7 ng/g of tissue) after 6 h of administration. The result suggested that Lf-conjugated 5.0 G PPI dendrimer-based formulations to be approximately 1.5 times and 2.5 times superior to plain 5.0 G PPI dendrimer as well as pure MTX, respectively, for lung targeting of anticancer drugs.

Pulmonary toxicity of carbon nanotubes: a systematic report.

Carbon nanotubes (CNTs) are nanosized cylindrical hollow tubes consisting entirely of the element carbon. Currently, CNTs are playing an important role in drug delivery as a carrier system because of their several unique physical and chemical properties. Studies show that CNTs are toxic and that the extent of that toxicity depends on properties of the CNTs, such as their structure (single wall or multiple wall), length and aspects ratios, surface area, degree of aggregation, extent of oxidation, bound functional group(s), method of manufacturing, concentration, and dose. People could be exposed to CNTs either accidentally by coming in contact with the aerosol form of CNTs during production or by exposure as a result of biomedical use. Numerous in vitro and in vivo studies have shown that CNTs and/or associated contaminants or catalytic materials that arise during the production process may induce oxidative stress, prominent pulmonary inflammation, apoptosis in different cell types, and induction of cytotoxic effects on lungs. Studies on the toxicity of CNTs have mainly focused on the pulmonary effects of intratracheal or pharyngeally administered CNTs. This review examines the potential pulmonary toxicity of CNTs. FROM THE CLINICAL EDITOR: Carbon nanotubes are promising drug delivery agents; however, their pulmonary toxicity may represent a substantial limitation to their applicability. This detailed review discusses critical aspects of the above problem.

Micro- and nanocarrier-mediated lung targeting.

IMPORTANCE OF THE FIELD: Drug delivery to lungs appears to be an attractive proposition on account of the large surface area of the alveolar region; it provides tremendous opportunities to improve drug therapies both systemically and locally using new drug delivery systems. Administration of drugs directly to the lungs is the most appropriate route in the treatment of asthma and other pulmonary diseases such as tuberculosis, chronic obstructive pulmonary disease and lung cancer. AREAS COVERED IN THIS REVIEW: This review focuses on the utilization of nano- and microcarriers such as microspheres, nanoparticles, liposomes, niosomes and dendrimers for targeted delivery of bioactive molecules to lungs. WHAT THE READER WILL GAIN: This review sheds light on the current status of nano- and microcarrier-mediated lung targeting of bioactive compounds. TAKE HOME MESSAGE: The literature review shows that carriers could supplement sustained drug delivery to the lungs, extended duration of action, reduced therapeutic dose, improved patient compliance, and reduced adverse effects of highly toxic drugs. There is still a need to identify more specific receptors that are present exclusively in the lungs. The identification of such receptors may also facilitate drug targeting to further specific parts of the lungs, such as bronchioles and alveoli.