Delivery of protein therapeutics is restricted to intravenous infusions due to protein-dependent problems including low solubilities, high viscosities, and physical instabilities. The ability to inject high concentrations of proteins via subcutaneous injections would increase accessibility and compliance. Large particles of a protein in a non-aqueous solvent can decrease the viscosity over a solution of equally concentrated individual protein molecules. The lower viscosity of a particle suspension is due to decreased surface area resulting in reduced electroviscous effects, solvation and deviations of the particle shape from a spherical geometry. Additional studies show that aqueous-based dispersions of antibody nanoclusters can be formed by increasing the attractive interactions between protein molecules using the excluded volume effects of extrinsic crowding agents. These novel, equilibrium, nanoclusters are maintained by a balance of highly attractive interactions and weak electrostatic repulsive interactions near the protein’s pI. These protein nanoclusters are ideal for subcutaneous delivery as they have low interactions between the colloids, are reversible in nature, and dissolve rapidly upon dilution in a buffer media. Through in vivo mouse studies, the bioavailability of a monoclonal antibody in the dispersion is prolonged and higher doses can be administered versus a solution. Overall, these studies with high concentration, low viscosity subcutaneous injections of protein therapeutics open new opportunities in biotechnology. For oral delivery of itraconzole, controlled flocculation of individual polymerically-stabilized nanoparticles is used to increase supersaturation. Flocculation of these nanoparticles is achieved by desolvating the polymer by changing the pH. The flocculated dispersions can then be easily filtered. The final amorphous powder maintains high supersaturation with simulated stomach and small intestine conditions and improves bioavailability of itraconazole, over the commercial product, Sporanox®. / text

Aditivos são amplamente utilizados em dietas ricas em concentrado para prevenir distúrbios metabólicos. A alga calcária, Lithothamnium calcareum, produto natural e renovável, fonte de carbonato de cálcio, pode ser uma alternativa na prevenção destes distúrbios. Este estudo foi desenvolvido para avaliar o efeito das fontes de cálcio, com ou sem monensina sódica na dieta, no controle da acidose ruminal de bovinos Nelore recebendo de forma abrupta uma dieta com elevada proporção (92,3%) de concentrado. Oito bovinos portadores de cânulas ruminais foram distribuídos em um delineamento quadrado latino (4x4) duplo. Os tratamentos foram a adição a dieta base com diferentes fontes de cálcio, calcário calcítico (CC) ou produto a base de alga calcária (AC), com (CMO) ou sem (SMO) a presença de monensina. A inclusão de CC, AC e monensina foi, respectivamente, de 7,1 g/kg, 7,4 g/kg e 30 mg/kg MS. Não houve efeito das fontes de cálcio e da monensina sobre o consumo alimentar e concentração total dos ácidos graxos de cadeia curta. Os tratamentos com AC resultaram em maior pH ruminal médio (P=0,039), menor tempo com pH ruminal abaixo de 5,2 (P<0,001) e um maior pH sanguíneo (P=0,006). Os tratamentos com monensina apresentaram menor tempo com pH ruminal abaixo de 5,2 (P=0.023). O produto a base de alga calcária pode ser uma boa alternativa para prevenir distúrbios metabólicos em animais submetidos a mudanças abruptas para dietas com elevada proporção de concentrado. / Additives are used in high concentrate diets in order to prevent metabolic disorders. Calcareous algae (Lithothamnium calcareum), a natural and renewable product, may be an alternative to prevent these disorders. This study was designed to evaluate the effect of calcium sources and monensin in the control of ruminal acidosis of Nellore cattle, abruptly fed a high (92.3%) concentrate diet. Eight cannulated steers were randomly assigned to a doubled 4x4 Latin square design. The treatments were the inclusion of different sources of calcium to the basic diet, limestone or calcareous algae, with or without the presence of monensin. The inclusion of limestone, calcareous algae and monensin was, respectively, 7.1 g/kg, 7.4 g/kg and 30mg/kg DM. There was on effect of calcium source (P=0.607) and monensin (P=0.294) on feed intake and in the short chain fatty acids concentration. Treatments with calcareous algae based product resulted in greater ruminal pH mean (P=0.039), lower time rumen pH remained below 5.2 (P<0.001) and better control of blood pH (P=0.006). Treatments with the presence of monensin also resulted in lower time of rumen pH below 5.2 (P=0.023). Calcareous algae may be an alternative to be used in pH control of beef cattle fed high concentrate diets.

Aditivos são amplamente utilizados em dietas ricas em concentrado para prevenir distúrbios metabólicos. A alga calcária, Lithothamnium calcareum, produto natural e renovável, fonte de carbonato de cálcio, pode ser uma alternativa na prevenção destes distúrbios. Este estudo foi desenvolvido para avaliar o efeito das fontes de cálcio, com ou sem monensina sódica na dieta, no controle da acidose ruminal de bovinos Nelore recebendo de forma abrupta uma dieta com elevada proporção (92,3%) de concentrado. Oito bovinos portadores de cânulas ruminais foram distribuídos em um delineamento quadrado latino (4x4) duplo. Os tratamentos foram a adição a dieta base com diferentes fontes de cálcio, calcário calcítico (CC) ou produto a base de alga calcária (AC), com (CMO) ou sem (SMO) a presença de monensina. A inclusão de CC, AC e monensina foi, respectivamente, de 7,1 g/kg, 7,4 g/kg e 30 mg/kg MS. Não houve efeito das fontes de cálcio e da monensina sobre o consumo alimentar e concentração total dos ácidos graxos de cadeia curta. Os tratamentos com AC resultaram em maior pH ruminal médio (P=0,039), menor tempo com pH ruminal abaixo de 5,2 (P<0,001) e um maior pH sanguíneo (P=0,006). Os tratamentos com monensina apresentaram menor tempo com pH ruminal abaixo de 5,2 (P=0.023). O produto a base de alga calcária pode ser uma boa alternativa para prevenir distúrbios metabólicos em animais submetidos a mudanças abruptas para dietas com elevada proporção de concentrado. / Additives are used in high concentrate diets in order to prevent metabolic disorders. Calcareous algae (Lithothamnium calcareum), a natural and renewable product, may be an alternative to prevent these disorders. This study was designed to evaluate the effect of calcium sources and monensin in the control of ruminal acidosis of Nellore cattle, abruptly fed a high (92.3%) concentrate diet. Eight cannulated steers were randomly assigned to a doubled 4x4 Latin square design. The treatments were the inclusion of different sources of calcium to the basic diet, limestone or calcareous algae, with or without the presence of monensin. The inclusion of limestone, calcareous algae and monensin was, respectively, 7.1 g/kg, 7.4 g/kg and 30mg/kg DM. There was on effect of calcium source (P=0.607) and monensin (P=0.294) on feed intake and in the short chain fatty acids concentration. Treatments with calcareous algae based product resulted in greater ruminal pH mean (P=0.039), lower time rumen pH remained below 5.2 (P<0.001) and better control of blood pH (P=0.006). Treatments with the presence of monensin also resulted in lower time of rumen pH below 5.2 (P=0.023). Calcareous algae may be an alternative to be used in pH control of beef cattle fed high concentrate diets.