Nanotechnology-Assisted Metered-Dose Inhalers (MDIs) for High-Performance Pulmonary Drug Delivery Applications.

PURPOSE: Respiratory disorders pose a major threat to the morbidity and mortality to public health. Here we reviewed the nanotechnology based pulmonary drug delivery using metered dose inhalers. METHODS: Major respiratory diseases such as chronic obstructive pulmonary diseases (COPD), asthma, acute lower respiratory tract infections, tuberculosis (TB) and lung cancer. At present, common treatments for respiratory disorders include surgery, radiation, immunotherapy, and chemotherapy or a combination. The major challenge is development of systemic delivery of the chemotherapeutic agents to the respiratory system. Conventional delivery of chemotherapy has various limitation and adverse side effected. Hence, targeted, and systemic delivery need to be developed. Towards this direction nanotechnology, based controlled, targeted, and systemic drug delivery systems are potential candidate to enhance therapeutic efficacy with minimum side effect. Among different route of administration, pulmonary delivery has unique benefits such as circumvents first pass hepatic metabolism and reduces dose and side effects. RESULTS: Respiratory disorders pose a major threat to the morbidity and mortality to public health globally. Pulmonary delivery can be achieved through various drug delivery devices such as nebulizers, dry powder inhalers, and metered dose inhalers. Among them, metered dose inhalers are the most interesting and first choice of clinician over others. This review focused on nanotechnology based pulmonary drug delivery using metered dose inhalers. This report focused on delivery of various types of therapeutics using nanocarriers such as polymeric nanoparticles and micelles, dendrimers, lipid nanocarriers such as liposomes, solid lipid nanostructures and nanostructured lipid carriers, and other using metered dose inhalers discussed comprehensively. This report provides insight about the effect of parameters of MDI such as co-solvent, propellants, actuators shape, nozzle diameters, and jet lengths, and respiratory flow rate, and particle size of co-suspension of drug on aerodynamics and lung deposition of formulation. This review also provided the insight about various metered dose inhalers market scenario and digital metered dose inhalers. CONCLUSION: This report concluded the clinical potential of metered dose inhalers, summary of current progress and future perspectives towards the smart digital metered dose inhalers development.

Amine-functionalized, porous silica-coated NaYF4:Yb/Er upconversion nanophosphors for efficient delivery of doxorubicin and curcumin.

Upconversion nanoparticles (UCNP) with unique multi-photon excitation photo-luminescence properties have been extensively explored as novel contrast agents for low-background biomedical imaging. There is an increasing interest in employing UCNPs as carrier for drug delivery as these offers a unique opportunity to combine therapy and diagnostics in one platform (theranostics). In the present work, we report microwave-assisted synthesis of hexagonal NaYF4:Yb/Er UCNPs coated with porous silica and functionalized with amine (UCNP@mSiO2). The UCNP@mSiO2 were investigated for controlled delivery of a chemotherapeutic agent, doxorubicin (DOX, hydrophilic), and a chemosensitizing agent, curcumin (CCM, hydrophobic). The drug loading was relatively higher for DOX (17.4%), in comparison to CCM (8.1%). The cumulative drug release from DOX-loaded UCNP@mSiO2 were 30 and 41% at physiological (7.4) and tumoral (6.4) pH, following a pseudo Fickian release pattern, whereas the release from CCM-loaded UCNP@mSiO2 were 27 and 50% at pH 7.4 and 6.4, following a non-Fickian and pseudo-Fickian release patterns, respectively. Both DOX and CCM-loaded UCNP@mSiO2 exhibited pH-dependent controlled drug delivery but the effect was more pronounced for CCM, the hydrophobic chemosensitizer. Cell viability assay using HeLa cells showed that DOX-loaded UCNP@mSiO2 inhibit cell growth in a dose-dependent manner, similar to free DOX, but the cell inhibition activity of free CCM was lower than CCM passively entrapped in UCNP@mSiO2. Confocal microscopy studies revealed cell uptake of both the drug by HeLa cells. Thus, UCNP@mSiO2 exhibited the unique capability to deliver hydrophilic and hydrophobic drugs, individually. UCNP@mSiO2 carrier, equipped with theranostic capabilities, may potentially be used for pH-responsive release of chemotherapeutic agents in cancer environment.

Biomimetic synthesis of silver nanoparticles from Streptomyces atrovirens and their potential anticancer activity against human breast cancer cells.

Silver nanoparticles (AgNPs) have been undeniable for its antimicrobial activity while its antitumour potential is still limited. Therefore, the present study focused on determining cytotoxic effects of AgNPs on Michigan cancer foundation-7 (MCF-7) breast cancer cells and its corresponding mechanism of cell death. Herein, the authors developed a bio-reduction method for AgNPs synthesis using actinomycetes isolated from marine soil sample. The isolated strain was identified by 16s ribotyping method and it was found to be Streptomyces atrovirens. Furthermore, the synthesised AgNPs were characterised by various bio-analytical techniques such as ultraviolet-visible spectrophotometer, atomic force microscopy, transmission electron microscopy, Fourier transform infra-red spectroscopy, and X-ray diffraction. Moreover, the results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay reveals 44.51 µg of AgNPs to have profound inhibition of cancer cell growth; furthermore, the inhibition of MCF-7 breast cancer cell line was found to be dose dependent on treatment with AgNPs. Acridine orange and ethidium bromide double staining methods were performed for cell morphological analysis. The present results showed that biosynthesised AgNPs might be emerging alternative biomaterials for human breast cancer therapy.