Abstract. The aim of this investigation was to develop and evaluate freeze-dried mannosylated liposomes for the targeted delivery of selenium. Dipalmitoylphosphatidylcholine, distearoylphosphatidylglycerol, and cholesterol were dissolved in a chloroform and methanol mixture and allowed to form a thin film within a rotatory evaporator. This thin film was hydrated with a sodium selenite (5.8 μM) solution to form multilamellar vesicles and homogenized under high pressure to yield unilamellar nanoliposomes. Seloaded nanoliposomes were mannosylated by 0.1%w/v mannosamine (Man-Lip-Se) prior to being lyophilized. Mannosamine concentration was optimized with cellular uptake studies in M receptor expressing cells. Non-lyophilized and lyophilized Man-Lip-Se were characterized for size, zeta potential, and entrapment efficiency. The influence of liposomal composition on the characteristics of Man-Lip-Se were evaluated using acidic and basic medium for 24 h. Thermal analysis and powder X-ray diffraction were used to determine the interaction of components within the Man-Lip-Se. The size, zeta potential and entrapment efficiency of the optimum Man-Lip-Se were observed to be 158±28.9 nm, 33.21±0.89 mV, and 77.27±2.34%, respectively. An in vitro Se release of 70-75% up to 24 h in PBS pH 6.8 and <8% Se release in acidic media (0.1 N HCl) in 1 h was observed. The Man-Lip-Se were found to withstand gastric-like environments and showed sustained release. Stable freeze-dried Man-Lip-Se were successfully formulated with a size of <200 nm, ∼75% entrapment, and achieved controlled release of Se with stability under acidic media, which may be of importance in the targeted delivery of Se to the immune system.

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Tornwaldt's cyst is a rare benign developmental lesion at the posterior wall of the nasopharynx. It develops from embryonic communication between anterior tip of the notochord and roof of the pharynx. Most patients are symptom-free, however, symptoms such as postnasal drip, nasal obstruction and earfullness can occur and the diagnosis may not be straightforward. Treatment involves the excision or wide marsupialization of the cyst, which has been performed transorally by adenoid currette, scissors, and so on. We report a Tornwaldt's cyst in a 25-year-old man who presented only blood tinged sputum. The cyst was successfully removed by endoscopic guided microdebrider.

RNAi technology has brought a new category of treatments for cancer. NFκB is a transcription factor which can inhibit apoptosis and promote cell proliferation. Activation of NFκB is linked to the progression of various cancers. Inhibition of NFκB and its downstream targets using NFκB-siRNA (NS) for cancer therapy has been investigated. However, for successful siRNA delivery, it has to be delivered into the cytoplasm of cancer cells. Naked siRNA is prone to degradation and has a plasma half-life of less than five minutes. In addition, the relatively small size of the siRNA leads to rapid renal clearance. These facts, together with the negatively charged siRNA which limits permeability across cell membrane, mean that successful delivery of naked siRNA is unlikely. Cationic lipid based systems have emerged as the most attractive siRNA delivery, however the use is limited due to poor transfection efficiency and toxicity. The use of polymers (polyethyleneimines and polyesteramines) has been hampered due to substantial toxicity. Natural polymer based delivery systems (chitosan, gelatin, albumin) are biocompatible and biodegradable with high physiological tolerance and low immunogenicity. The purpose of this study was to develop NS loaded into gelatin nanocarriers (NS-GNCs) that enables effective delivery in a targeted fashion to tumors. The NS-GNCs were prepared using cationic gelatin by desolvation method. The NS-GNCs were characterized for size, charge, entrapment, release and in vitro efficacy against lung and breast cancer cells. The size and zeta potential was found to be 180 ± 4 nm and 16 ± 2 mV respectively. Entrapment efficiency was found to be 81 ± 1.4 % and the release of siRNA was in a controlled manner up to 48 h. The dose dependent in vitro efficacy of NS-GNCs was studied using A549 lung cancer and MDA-MB-231 breast cancer cells compared to naked NS using untreated cells as a control. NS-GNCs showed significantly (p&lt;0.05) higher cytotoxicity against lung and breast cancer cells in a dose dependant manner compared to naked NS. At 30ng/ml, NS-GNCs treated A549 cells showed 46% cytotoxicity compared to 16% in naked NS treated A549 cells. At 60ng/ml, NS-GNCs treated MDA-MB-231 cells showed 54% cytotoxicity compared to 21% in naked NS treated cells. The increased cytotoxicity with NS-GNCs can be attributed to the tumor specific accumulation of positively charged GNCs by uptake through electrochemical diffusion. Moreover, NS-GNCs showed comparable cytotoxicity as compared to lipofectamine (tranfecting agent) in both the cancer cells. The developed targeted NS-GNCs showed enhanced activity compared to naked NS against cancer cells. This innovative delivery approach will help to overcome the limitations and adverse side effects associated with current delivery approaches. We are currently investigating NS-GNC conjugation with RGD peptide to enhance the tumor specific delivery via receptor mediated endocytosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5644. doi:1538-7445.AM2012-5644

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