Mannitol Carrier Research Articles

TAILORING DRY POWDER INHALER PERFORMANCE BY MODIFYINGCARRIER SURFACE TOPOGRAPHY BY SPRAY DRYING

In order to provide adequate performance of dry powder inhalates with respect to dosing and fine particle fraction, interparticle adhesion between drug and carrier has to be well balanced. It has to be large enough to ensure attachment of the active ingredient during powder handling and dosing, but small enough to ensure detachment of the drug from the carrier on inhalation. In this study, interparticle interactions have been modified by targeting the surface topography of the carrier or rather the contact area between drug and carrier using spray drying. Because lactose is susceptible to spray drying, resulting in partial or full amorphicity, mannitol was used here. The spray drying outlet temperature turned out to be an appropriate parameter to affect surface topography, spray drying at low temperature leading to smooth particles, and spray drying at high temperature leading to rough particle surfaces. Dosing of the inhalate was found not to be affected by surface roughness of the carrier. However, the fine particle fraction decreases with increasing surface roughness. Consequently, the use of mannitol carrier particles exhibiting different surface topographies allows for modifying interparticle interactions, thereby providing an effective tool for tailoring the performance of an inhalate.

Design and evaluation of diclofenac sodium controlled drug delivery systems

Sustained release dosage form of diclofenac sodium containing immediate and controlled release components was designed. Solid dispersion of immediate release component was prepared using polyvinyl pyrrolidone and mannitol carriers by common solvent method. Controlled release component was prepared in form of spherical beads by ionotropic gelation technique. The beads were prepared based on dispersing drug in solutions of ionic polysaccharides such as chitosan and sodium alginate. These dispersions were dropped into solutions of counter ions such as tetrasodium pyrophosphate and calcium chloride, respectively. The beads were also prepared using agar by dropping agar-drug hot solution into a mixture of chilled liquid paraffin and water. Then, diclofenac sodium controlled release drug delivery systems were prepared by combining the immediate release and controlled release components in different ratios. The formulations were found to be effective in providing controlled release of drug for a longer period of time. The beads were characterized by scanning electron microscopy and X-ray diffraction studies.

Utilization and Transport of Mannitol in Olea europaea and Implications for Salt Stress Tolerance

Mannitol is one of the primary photosynthetic products and the major phloem-translocated carbohydrate in Olea europaea L., an important crop in the Mediterranean basin. Uptake of mannitol in heterotrophic cell suspensions of O. europaea was shown to be mediated by a 1 : 1 polyol : H+ symport system with a Km of 1.3 mM mannitol and a Vmax of 1.3 nmol min(-1) mg(-1) DW. Dulcitol, sorbitol and xylitol competed for mannitol uptake, whereas glucose and sucrose did not. Reverse transcription-PCR (RT-PCR) performed on mRNA extracted from cultured cells exhibiting high mannitol transport activity allowed the cloning of a partial O. europaea mannitol carrier OeMaT1. The Vmax of mannitol uptake and the amount of OeMaT1 transcripts increased along with polyol depletion from the medium, suggesting that the mannitol transport system may be regulated by its own substrate. Addition of 100-500 mM NaCl to cultured cells enhanced the capacity of the polyol : H+ symport system and the amount of OeMaT1 transcripts, whereas it strongly repressed mannitol dehydrogenase activity. Measurements of cell viability showed that mannitol-grown cells remained viable 24 h after a 250 and 500 mM NaCl pulse, whereas extensive loss of cell viability was observed in sucrose-grown cells. OeMaT1 transcripts increased throughout maturation of olive fruits, suggesting that an OeMaT is involved in the accumulation of mannitol during ripening of olive. Thus, mannitol transport and compartmentation by OeMaT are important to allocate this source of carbon and energy, as well as for salt tolerance and olive ripening.

Liposomal dry powders as aerosols for pulmonary delivery of proteins

The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. Beta-glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7:3) was selected as the liposome composition. The lyophilization of liposomes, micronization of the powders, aerosolization using a dry powder inhaler (DPI), and in vitro aerodynamic fine particle fraction upon collection in a twin-stage liquid impinger were evaluated. After lyophilization and jet-milling, the total amount of GUS and its activity, representing encapsulation efficiency and stability, were evaluated. The GUS amount and activity were measured and compared with freshly-prepared liposomes in the presence of mannitol, 43% of initial GUS amount, 29% of GUS activity after lyophilization and 36% of GUS amount, 22% of activity after micronization were obtained. Emitted doses from dry powder inhaler were 53%, 58%, 66%, and 73% for liposome powder:mannitol carrier ratios of 1:0, 1:4, 1:9, and 1:19. Fifteen percent of the liposome particles were less than 6.4 mum in aerodynamic diameter. The results demonstrate that milled liposome powders containing protein molecules can be aerosolized effectively at a fixed flow rate. Influences of different cryoprotectants on lyophilization of protein liposome formulations are reported. The feasibility of using liposomal dry powder aerosols for protein delivery has been demonstrated but further optimization is required in the context of specific therapeutic proteins.

Mannitol transport by vacuoles of storage parenchyma of celery petioles operates by facilitated diffusion

Summary The sugar alcohol mannitol is the main water-soluble carbohydrate of the storage parenchyma of celery petioles. Compartmentation studies had indicated that mannitol was about equally distributed between the large central vacuole and the cytosol of these cells (Keller, F. and P. Matile, New Phytol., 113, 291–299 [1989]). Evidence is now presented for a tonoplast-bound mannitol carrier that operates by facilitated diffusion, i.e. protein-mediated and passively. With isolated parenchyma vacuoles it was shown that the uptake rate of mannitol, at 1 mmol/L external concentration, was about twice that of L-glucose and glucitol (sorbitol), both established markers for simple diffusion. Mannitol uptake was a saturable process with apparent K m and V max values of 14 mmol/L and 0.067 nmol/μL vacuoles · min, respectively. It was also quite specific as indicated by competition studies with glucitol, galactitol, glucose, and fructose. The functionality of the mannitol carrier was unaffected by three protein-modifying reagents, the sulfhydryl group modifiers p -chloro mercuribenzenesulfonic acid (PCMBS) and N -ethylmaleimide (NEM) and the histidine modifier diethyl pyrocarbonate (DEPC). Mannitol uptake was neither stimulated by energization with ATP or pyrophosphate nor was it impaired by dissipation of the pH gradient or the membrane potential and is, therefore, passive. The implications of this facilitated diffusion mechanism for the proposed physiological functions of mannitol in celery are discussed.

Carbohydrate transport in discs of storage parenchyma of celery petioles: 2. Uptake of mannitol.

The sugar alcohol mannitol is, together with glucose and fructose, the main soluble carbohydrate of celery petioles. It is accumulated in the storage parenchyma of mature petioles and remobilized during senescence. The mechanisms of mannitol uptake into discs isolated from petiole parenchyma was studied. Uptake kinetics showed a biphasic response to increasing external concentrations of [14 C]D-mannitol with a predominant saturable component at low concentrations (below about 2 mM) and a linear component at higher concentrations (at least up to 16 mM). The saturable component showed an apparent Km of about 1 mM and a fairly sharp pH optimum around pH 6-5. It was stimulated by the plasmalemma H+ -ATPase stimulator FC and inhibited by the SH-reagents PCMBS and NEM and the uncoupler DNP. CCCP was also inhibitory, but its effect could be reversed by DTT, suggesting a dual role of CCCP as SH-reagent and uncoupler in this tissue. Competition studies with 14-different polyols and sugars showed that uptake was very specific. The saturable uptake component was clearly turgor-dependent. Lowering of cell turgor by treatment of increasing concentrations of the relatively nonpermeant glycinebetaine (0 to 0.8 M) resulted in a linear increase of Vmax and an unaltered Km . It is concluded that celery petiole parenchyma contains at least a mannitol carrier at the plasmalemma which operates in an active proton-cotransport manner. It is speculated that a superimposed mannitol carrier is present at the tonoplast and might operate by facilitated diffusion.