Silver nanoparticles as a new generation of antimicrobials.

Biodegradable polymeric nanoparticles based drug delivery systems

Hydrogel Nanoparticles in Drug Delivery

In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility (at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half-life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real-time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next-generation platform for cancer therapy and many other biomedical applications.

Engineered Nanoparticles for Drug Delivery in Cancer Therapy

"Nanoantibiotics": a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era.

Objectives: To improve the bioavailability of antitubercular drugs (ATDs) as well as to assess the feasibility of administering ATDs via the respiratory route, this study reports the formulation of three frontline ATDs, i.e. rifampicin, isoniazid and pyrazinamide encapsulated in poly (DL-lactide-co-glycolide) nanoparticles suit- able for nebulization. Methods: Drug-loaded nanoparticles were prepared by the multiple emulsion technique, vacuum-dried and nebulized to guinea pigs. The formulation was evaluated with respect to the pharmacokinetics of each drug and its chemotherapeutic potential in Mycobacterium tuberculosis infected guinea pigs. Results: The aerosolized particles exhibited a mass median aerodynamic diameter of 1.88 ± 0.11 µm, favour- able for bronchoalveolar lung delivery. A single nebulization to guinea pigs resulted in sustained thera- peutic drug levels in the plasma for 6-8 days and in the lungs for up to 11 days. The elimination half-life and mean residence time of the drugs were significantly prolonged compared to when the parent drugs were administered orally, resulting in an enhanced relative bioavailability (compared to oral administration) for encapsulated drugs (12.7-, 32.8- and 14.7-fold for rifampicin, isoniazid and pyrazinamide, respectively). The absolute bioavailability (compared to intravenous (iv) administration) was also increased by 6.5-, 19.1- and 13.4-fold for rifampicin, isoniazid and pyrazinamide, respectively. On nebulization of nanoparticles contain- ing drugs to M. tuberculosis infected guinea pigs at every 10th day, no tubercle bacilli could be detected in the lung after five doses of treatment whereas 46 daily doses of orally administered drug were required to obtain an equivalent therapeutic benefit.

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Poly (dl-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis

Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis

Oral solid lipid nanoparticle-based antitubercular chemotherapy.

Background. Reduction in the dosing frequency of antituberculosis drugs (ATDs) by applying drug delivery technology has the potential to improve the patient compliance in tuberculosis (TB). Alginate (a natural polymer) based nanoparticulate delivery system was developed for frontline ATDs (rifampicin, isoniazid, pyrazinamide and ethambutol). Methods. Alginate nanoparticles were prepared by the controlled cation induced gelification method and administered orally to mice. The drug levels were analysed by high performance liquid chromatography (HPLC) in plasma/tissues. The therapeutic efficacy was evaluated in M. tuberculosis H 37 Rv infected mice. Results. High drug encapsulation efficiency was achieved in alginate nanoparticles, ranging from 70%-90%. A single oral dose resulted in therapeutic drug concentrations in the plasma for 7-11 days and in the organs (lungs, liver and spleen) for 15 days. In comparison to free drugs (which were cleared from plasma/organs within 12-24 h), there was a significant enhancement in the relative bioavailability of encapsulated drugs. In TB-infected mice three oral doses of the formulation spaced 15 days apart resulted in complete bacterial clearance from the organs, compared to 45 conventional doses of orally administered free drugs. Conclusions. Alginate nanoparticles appear to have the potential for intermittent therapy of TB.

Rajesh Pandey

Papers

Poly (dl-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis

Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis

Oral solid lipid nanoparticle-based antitubercular chemotherapy.

Alginate nanoparticles as antituberculosis drug carriers : Formulation development, pharmacokinetics and therapeutic potential

Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis