This can be achieved by further engineering of these nanovesicles to result in their partial absorption into systemic circulation, following their aerosol delivery in lungs. The nanovesicles absorbed in systemic circulation can then passively accumulate in metastatic tumors in other organs by EPR effect. Further studies are therefore required to successfully translate this strategy in clinics for the treatment of melanoma metastases.
Taxol was purchased from Cipla Ltd. India and Abraxane was purchased from Biocon India. Dialysis membrane molecular wt. Rhodamine-6G was purchased from Anaspec Inc. Both blank and paclitaxel loaded lipid nanovesicles LN-PTX were prepared by modified thin film hydration method 21 , Encapsulation and loading efficiency of paclitaxel in the nanovesicles was determined by breaking them open using methanol and quantifying the drug using reverse phase HPLC Agilent Binary LC pump liquid chromatograph In vitro release of paclitaxel from LN-PTX was studied by dialysis bag method 41 , both under normal physiological condition pH 7.
We performed membrane stability studies using DPPC monolayer as the model cell membrane 42 , DPPC monolayer model was created as described previously Surface pressures were then recorded as a function of time till seconds. In order to obtain the effects of drug penetration alone, the surface pressure of the monolayer over time was monitored without any formulation and these values were deducted from the corresponding ones on addition of the formulation. Cells treated with medium only served as control. Cell viability was measured using the formula:.
IC 50 values for all the formulations were calculated using GraphPad Prism 4 software.
Cellular uptake of the nanovesicles by B16F10 cells was studied at three different time points viz. To understand the mechanism of cellular uptake, cells were incubated in the presence of Rh-6G loaded nanovesicles in normal and ATP depleted conditions ATP depleted conditions were obtained by pre incubation of cells in the presence of metabolic inhibitor i.
Inflammatory response of alveolar macrophages to nanovesicles was evaluated in vitro using RAW Animals were provided by Piramal Life Sciences Ltd. Animals were divided into two groups with six animals in each. Aerosol was administered for a period of 30 minutes to the entire group of mice placed in sealed and transparent plastic chamber.
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Three mice from each group were sacrificed by cervical dislocation at different time points viz. On day 1, mice were randomly divided into four groups, each having six animals in it. The last group group D was kept as control, which received 0. All aerosol treatments were given 5 days a week for four weeks and intravenous treatments were given once in three days for four weeks.
Structure and design of polymeric surfactant-based drug delivery systems.
Body weights were taken intermittently during the entire experiment. Lungs were resected, weighed and fixed in formalin.
Metastases inhibition potential was evaluated on the basis of percentage inhibition in the increase of lung weight due to the metastasized tumor in comparison to the animals treated with 0. Tumor nodules on the lungs were counted using stereomicroscope. Statistical significance of the data was analyzed by Student's t -test. Videira, M. Preclinical evaluation of a pulmonary delivered paclitaxel-loaded lipid nanocarrier antitumor effect.
Nanomedicine 8 , — Koshkina, N. Paclitaxel liposome aerosol treatment induces inhibition of pulmonary metastases in murine renal carcinoma model. Clin Cancer Res 7 , — Distribution of camptothecin after delivery as a liposome aerosol or following intramuscular injection in mice.
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Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A2. J Lipid Res 46 , — Kaviratna, A. Nanovesicle aerosols as surfactant therapy in lung injury. Perez-Gil, J. Structure of pulmonary surfactant membranes and films: the role of proteins and lipid-protein interactions.
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- Structure and design of polymeric surfactant-based drug delivery systems.
- Surfactants: Pharmaceutical and Medicinal Aspects.
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- Recent Advances in Drug Delivery of Polymeric Nano-Micelles.
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Journal of Pharmaceutical Sciences 98 6 : , This concentration is called CMC. CMC - The concentration of monomer at which the micelles are start to form in solvent at particular temperature. Micelles form only when the concentration of surfactant is greater than the critical micelle concentration CMC. Micelles are divided into Monomeric micelle, Reverse micelle, Polymeric micelle depending upon the type of the solvent polar and non-polar used for the formation of micelle. By contrast, surfactant monomers are surrounded by water molecules that create a "cage" of molecules connected by hydrogen bonds.
This water cage is similar to ice-like crystal structure. Micelles are dynamic species; there is a constant rapid interchange of surfactant molecules between the micelle and the bulk solution. Micelles cannot, therefore, be regarded as rigid structures with a defined shape, although an average micellar shape may be considered and Micelles are labile entities formed by the non-covalent aggregation of individual surfactant monomers.
Therefore, they can be spherical, cylindrical, or planar discs or bilayers. Micelle shape and size can be controlled by changing the surfactant chemical structure as well as by varying solution conditions such as temperature, overall surfactant concentration, surfactant composition in the case of mixed surfactant systems , ionic strength and pH. In particular, depending on the surfactant type and on the solution conditions, spherical micelles can grow one-dimensionally into cylindrical micelles or two-dimensionally into bilayers or discoidal micelles.
Spherical micelles exist at conc. At higher conc. Micelle growth is controlled primarily by the surfactant heads, since both one dimensional and two dimensional growth require bringing the surfactant heads closer to each other in order to reduce the available area per surfactant molecule at the micelle surface, and hence the curvature of the micelle surface.
In polar solvent , the hydrophilic "heads" of surfactant molecules are always in contact with the sequestering solvent and the hydrophobic single tail regions in the micelle centre called normal micelle oil-in-water micelle. This phase is caused by the insufficient packing issues of single tailed lipids in a bilayer.
The difficulty filling all the volume of the interior of a bilayer, while accommodating the area per head group forced on the molecule by the hydration of the lipid head group leads to the formation of the micelle. One of the most important applications of micellization in the context of pharmaceuticals is their ability to solubilize drugs of poor aqueous solubility. Micelle In Polar Solvent . Dipole—dipole interactions hold the hydrophilic heads of the surfactant molecules together in the core, and in certain cases hydrogen bonding between head groups can also occur.