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Human serum albumin (HSA) nanoparticles are considered to be versatile carrier of anticancer agents in efficiently delivering the drug to the tumor site without causing any toxicity. The aim of the study was to develop stable HSA nanoparticles (NPs) of drug irinotecan (Iro) having slightly water solubility and moderate HSA binding. A novel strategy of employing a hydrophilic non-ionic surfactant polysorbate 80 which forms protein-polysorbate 80 complex with increased affinity and improvement in Iro-HSA binding has been used to maximize the loading and entrapment efficiency of Iro in HSA-NPs. Bespoke nanoparticles with entrapment efficiency (79.09%) and drug loading of 9.62% could be achieved with spherical shape and particle size of 77.38 nm, 0.290 polydispersity index and -23.7 mv Zeta potential. The drug entrapment in nanoparticles was confirmed by Differential Scanning Calorimeter, Fourier Transformation Infrared Spectroscopy and Fluorescence Spectroscopy. In vitro release of Iro from NPs showed biphasic-release with initial burst followed by prolonged release upto 24 h. The short-term stability investigation of nanodispersion showed no significant changes in physicochemical properties of NPs. Long-term studies on freeze dried Iro-HSA-NPs indicated good stability of NPs up to 12 months. This is the first report for efficient fabrication of Iro delivery system based on HSA nanoparticles.

A pH‐responsive dendrimer templated polymer‐calcium phosphate core shell nanostructure is developed. Upon exposure to cellular lysosomal pH, a guest anticancer drug is released from the nanocapsule by dissolution of the CaP shell. Such a stimuli responsive carrier enables on‐demand controlled release of drugs in acidic organelles.

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Advanced delivery systems, such as nano/micro carriers have not been studied significantly for their molecular interactions with serum proteins and other biologically relevant macromolecules. Here, we investigated the effect of surface chemistry of iron oxide (Fe3O4) nanoparticles on molecular interactions with human insulin by fluorescence, XRD and FTIR spectroscopy. Nanoparticles of Fe3O4 were chemically modified as Fe3O4-glutathione (GSH) and Fe3O4-GSH-polyamidoamine generation 4 (PAMAM G4) dendrimer. Our results demonstrate that, Fe3O4 and its conjugates such as Fe3O4-GSH, Fe3O4-GSH-G4 quenched insulin fluorescence, indicating strong interactions between insulin protein molecule and Fe3O4. The fluorescence quenching constants Ksv were obtained as 0.0367 x 10(3), 0.0303 x 10(3) and 0.0131 x 10(3) M and the binding constant K were found to be 27.095, 8.404 and 6.026 mM for Fe3O4, Fe3O4-GSH and Fe3O4-GSH-PAMAM G4, respectively. Both the Ksv and K (binding constant) values revealed that the interaction of Fe3O4 with insulin to be stronger over to dendrimer conjugates. In addition, the FTIR spectra suggested that the presence of nanoparticles results in secondary structure alteration in the insulin conformation. The study implies the critical evaluation of new delivery systems in establishing the biocompatibility, especially when delivered by systemic route.

Irinotecan (IRT) is an antineoplastic agent widely used in the treatment of various cancers primarily in colorectal cancer. A new, simple and sensitive high-performance liquid chromatography (HPLC) method coupled with fluorescence detector was developed and validated to quantify IRT and its active metabolite SN38 in the plasma of non-obese diabetic/severe combined immune-deficient mice (NOD/SCID) mice bearing colon tumor. The plasma samples were extracted by precipitation method using acetonitrile with 0.1% formic acid. The chromatographic separation was achieved using mobile phase consisted of water and acetonitrile (57:43 v/v) pH 3 at the flow rate of 0.8 mL/min in C18 column (internal diameter, 250 × 4.6 mm; pore size, 5 μm). The method was validated according to the bioanalytical guidelines defined by Food and Drug Administration (FDA) and European Medicine Agency (EMA). A regression (R 2 ) value of 0.999 and 0.997 for IRT and SN38 suggested the good linearity in the range of 0.1-10 μg/mL and 5-500 ng/mL, respectively. The calculated lower limit of quantification (LLOQ) and limit of detection (LOD) for IRT were 0.1 and 0.065 μg/mL, respectively. However, for SN38, LLOQ and LOD were 5 and 2 ng/mL, respectively. The intra-day and inter-day variations (coefficient of variance; % CV) observed during the validation were found to be within the set limit of 15%. Both accuracy and percentage recovery analyzed and calculated from the quality control samples were in the between the defined range of 85-115%. Plasma samples were found to be stable when stored at room temperature for 2 h, after 2 freeze-thaw cycles and at −80°C for 2 months. The developed method was successfully applied to study the plasma elimination profile of IRT in NOD/SCID mice with tumor. The results from plasma concentration time profile and pharmacokinetic parameter analyzed suggested the rapid elimination of IRT and SN38 from the plasma of NOD/SCID mice.