Advances in ophthalmic drug delivery

Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient’s lifetime

Glucose-6-phosphate dehydrogenase partitioning in two-phase aqueous mixed (nonionic/cationic) micellar systems

The enzyme glucose-6-phosphate dehydrogenase (G6PD) plays an important role in maintaining the level of NADPH and in producing pentose phosphates for nucleotide biosynthesis. It is also of great value as an analytical reagent, being used in various quantitative assays. In searching for new strategies to purify this enzyme, the partitioning of G6PD in two-phase aqueous mixed (nonionic/cationic) micellar systems was investigated both experimentally and theoretically. Our results indicate that the use of a two-phase aqueous mixed micellar system composed of the nonionic surfactant C10E4 (n-decyl tetra(ethylene oxide)) and the cationic surfactant C(n)TAB (alkyltrimethylammonium bromide, n = 8, 10, or 12) can improve significantly the partitioning behavior of G6PD relative to that obtained in the two-phase aqueous C10E4, micellar system. This improvement can be attributed to electrostatic attractions between the positively charged mixed (nonionic/cationic) micelles and the net negatively charged enzyme G6PD, resulting in the preferential partitioning of G6PD to the top, mixed micellerich phase of the two-phase aqueous mixed micellar systems. The effect of varying the cationic surfactant tail length (n = 8, 10, and 12) on the denaturation and partitioning behavior of G6PD in the C10E4/C(n)TAB/buffer system was investigated. It was found that C,TAB is the least denaturing to G6PD, followed by C(10)TAB and C(12)TAB. However, the C10E4/C(12)TAB/buffer system generated stronger electrostatic attractions with the net negatively charged enzyme G6PD than the C10E4/ C(10)TAB/buffer and the C10E4/C(8)TAB/buffer systems, when using the same amount of cationic surfactant. Overall, the two-phase aqueous mixed (C10E4/C(10)TAB) micellar system yielded the highest G6PD partition coeficient of 7.7, with a G6PD yield in the top phase of 71%, providing the optimal balance between the denaturing effect and the electrostatic attractions for the three cationic surfactants examined. A recently developed theoretical framework to predict protein partition coefficients in two-phase aqueous mixed (nonionic/ionic) micellar systems was implemented, and the theoretically predicted G6PD partition coefficients were found to be in reasonable quantitative agreement with the experimentally measured ones. (C) 2003 Wiley Periodicals, Inc

L-Asparaginase Encapsulation into Asymmetric Permeable Polymersomes

This work reports, for the encapsulation of l-asparaginase, an anticancer enzyme into hybrid PMPC25–PDPA70/PEO16–PBO22 asymmetric polymersomes previously developed by our group, with loading capacities with over 800 molecules per vesicle. Enzyme-loaded polymersomes show permeability and capacity to hydrolyze l-asparagine, which is essential to cancer cells. The nanoreactors proposed in this work can be potentially used in further studies to develop novel therapeutic alternatives based on l-asparaginase

Green fluorescent protein extraction and LPS removal from Escherichia coli fermentation medium using aqueous two-phase micellar system

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The viability of large-scale industrial production of recombinant biomolecules of pharmaceutical interest significantly depends on the separation and purification techniques used. In biotechnology, endotoxin (LPS) removal from recombinant proteins is a critical and challenging step in the preparation of injectable therapeutics, since endotoxin is a natural component of bacterial expression systems widely used to manufacture therapeutic proteins. This work aimed to study the use of aqueous two-phase micellar systems (ATPMS) from preparations containing recombinant proteins of pharmaceutical interest, such as green fluorescent protein (GFPuv), which works as a biological indicator. The GFPuv extraction and LPS removal were evaluated in ATPMS, partition assays were carried out using pure GFPuv and cell lysate from Escherichia coli. The ATPMS technology proved to be effective in GFPuv recovery, preferentially into the micelle-poor phase (K(GFPuv) > 1), and LPS removal into the micelle-rich phase (%REM(LPS) > 98%). GFPuv was partitioned preferentially into the micelle-poor phase due to excluded-volume interactions in the micelle-rich phase. Therefore, this system can be exploited as the first step for purification in biotechnology processes for removal of higher LPS concentrations. (C) 2011 Elsevier B.V. All rights reserved.813339346Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Extraction of eco-friendly and biodegradable surfactant for inhibition of copper corrosion during acid pickling

A novel, cheap, less toxic, and easier-prepared gelatin surfactant is successfully used as corrosion inhibitor for the corrosion of copper in 0.1 M H 2 SO 4 at the temperature range: 25–55°C. The critical micelle concentration of the surfactant was determined from surface tension measurements. The inhibition efficiency was determined from potentiodynamic polarization and electrochemical impedance spectroscopy techniques. For surfactant acted by adsorption at copper/solution interface, an inhibition efficiency up to 68 was obtained at critical micelle concentration (70 ppm) of surfactant at 35°C. The free energy of adsorption was calculated and discussed. The surface parameters of gelatin surfactant were calculated and correlated to the inhibition efficiency. They were also calculated from its surface tension profile including: critical micelle concentration), maximum surface excess (Γ max ), and minimum surface area (A min ). The thermodynamic of micellization, free energies of micellization (ΔG mic ) and entropy of micellization, was calculated and discussed. The formation of compact and adherent monomolecular adsorbed film on copper substrate was confirmed