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After intravenous (i.v.) injection, colloidal drug carriers such as liposomes, emulsions, polymeric or solid lipid nanoparticles immediately interact with plasma proteins. The adsorbed plasma protein patterns depend on physico-chemical characteristics of the carriers' surface and are regarded as a key factor for the in vivo behavior of the carriers. The comprehension of the correlation between protein adsorption and in vivo organ distribution can be utilized to obtain drug targeting to different tissues. Carriers with different protein adsorption patterns will interact with different tissue-specific receptors or will be recognized by different macrophage subpopulations. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was applied to determine the protein adsorption patterns on polystyrene particles as model carriers. To transfer this analytical method to i.v. injectable colloidal carriers such as liposomes, a new sample preparation method was developed. The separation of liposomes from plasma after incubation was achieved by gel filtration using a Sepharose 2B column. This technique allowed a mild separation independent from eluent composition and only according to size differences. Possible protein desorption from the liposomes and adsorption onto the gel were minimized by using an eluent with a sufficiently high ionic strength. To estimate the efficiency of separation, the content of liposomes and plasma in each fraction being eluted was determined by ultraviolet (UV) spectroscopy. With this new separation method plasma protein adsorption patterns on liposomes could be analyzed for the first time. The sample preparation by gel filtration seemed to have no influence on liposome stability as far as size distribution is concerned.

The disappointing results with either surgery alone and/or chemotherapy in the treatment of malignant ovarian tumours have led to an increased interest in additional treatment schedules. Photodynamic therapy (PDT), a modality involving the use of a photosensitising drug and activating light, is being used increasingly as a local treatment for neoplastic lesions. The synthesis and evaluation of new photosensitisers for the treatment of gynaecological lesions and malignancies continues to be an active area of investigation for proper application of the photodynamic process in the gynaecological field. The effect of PDT using methylene blue (free and combined with liposomes) as a photosensitiser for treating human ovarian malignant tumours cultivated on the chorioallantoic membrane was evaluated. Two days after PDT, the treated implanted tumours were markedly decreased in size. Areas of necrosis with black coloration, dryness and eschar formation were observed. Five days after PDT, tumour remission was clearly observed in all the treated tumours. Photodynamic therapy using methylene blue (aqueous and coupled with liposomes) is effective for treating the ovarian malignancies and it will be capable of achieving complete eradication of visible tumours in patients with superficial lesions.

Amikacin-loaded liposomes were produced and surface-modified by adsorption of PEG 4000, Tween 80, poloxamer 407 and gelatin. The organ distribution was studied in mice by analysing the amikacin content in liver, spleen, lung, kidneys and serum. Highest serum levels were obtained with the PEG- and Tween 80 modified liposomes (at 2 hours p.inj.). Modification of the liposomes with gelatin as opsonization promoting agent distinctly increased the amikacin concentration in the liver from 36 to 66 mg/kg. Highest spleen concentrations were observed with non-modified and poloxamer 407 liposomes (242 mg/kg and 248 mg/kg, respectively). The data suggest that modification by a simple adsorption process is sufficient to effectively alter the organ distribution. The liposomes differing in organ distribution exhibited also different plasma protein adsorption patterns, up to 115 spots were detected by 2-D PAGE. Hydrophilic albumin was present in a conc. of appr. 80% on liposomes modified with ethoxylated compounds. On the gelatin liposomes, 14% of alpha-2-Macroglobulin were adsorbed which is a protein typically found on particles rapidly cleared by the RES. IgM, Apo A-I, Apo C-II and alpha-1-Antitrypsin were other detected proteins.

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