Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to t...Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties,therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal(GI)tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drugdelivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.展开更多
Background: Postprandial plasma glucose concentration is an important diabetes management target. Glycemia-targeted specialized-nutrition (GTSN) beverages, containing various quantities and types of carbohydrates (CHO...Background: Postprandial plasma glucose concentration is an important diabetes management target. Glycemia-targeted specialized-nutrition (GTSN) beverages, containing various quantities and types of carbohydrates (CHO), have been formulated to blunt postprandial hyperglycemia. The objective of this research was to evaluate the effectiveness of these products on postprandial glycemic and hormonal responses based on comparisons of GTSN with differing carbohydrate quantities or types. Methods: In two randomized, double-blind, crossover studies, participants (mean age 61 years) with type 2 diabetes consumed GTSN in a meal tolerance test. In the CHO Quantity Study, a standard nutritional beverage (STD) was compared to a low carbohydrate nutritional beverage with tapioca dextrin (GTSN-TDX) and a balanced carbohydrate nutritional beverage containing a blend of the slowly-digesting carbohydrates maltodextrin and sucromalt (GTSN-SDC). In the CHO Type Study, the GTSN beverages had similar carbohydrate quantities but varied in carbohydrate composition with GTSN-SDC compared to a formula with tapioca starch and fructose (GTSN-TS&F), and one with isomaltulose and resistant starch (GTSN-I&RS). Postprandial (0-240 min) concentrations of blood glucose, insulin (CHO Quantity Study only) and glucagon-like-peptide (GLP)-1 (CHO Quantity Study only) were measured. Results: Despite having substantially different carbohydrate quantities, the GTSN blunted the glucose positive area under the curve (AUC0-240 min) by 65% to 82% compared to the STD formulation (p < 0.001). GTSN also elicited ~50% lower insulin positive AUC0-240 min (p < 0.05), while postprandial GLP-1 responses were increased (p = 0.018) vs. STD. In the CHO Type Study, glucose positive AUC0-240 min tended to be lower for GTSN-SDC (1477 ± 460) than GTSN-TS&F (2203 ± 412;p = 0.062) and GTSN-I&RS (2190 ± 412;p = 0.076). No differences were observed between GTSN-TS&F and GTSN-I&RS. Conclusions: These results demonstrate the effectiveness of several GTSN products and suggest 展开更多
基金supported in part by a grant from the National Institutes of Health (R01-EB-00246020)the Cockrell Family Regents Chair. Angela M.Wagner was supported by a National Science Foundation Graduate Research Fellowship (DGE-1610403)+1 种基金the S.E.S.H.A. Endowed Graduate Fellowship in Engineeringthe Philanthropic Educational Organization Scholar Award
文摘Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties,therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal(GI)tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drugdelivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.
文摘Background: Postprandial plasma glucose concentration is an important diabetes management target. Glycemia-targeted specialized-nutrition (GTSN) beverages, containing various quantities and types of carbohydrates (CHO), have been formulated to blunt postprandial hyperglycemia. The objective of this research was to evaluate the effectiveness of these products on postprandial glycemic and hormonal responses based on comparisons of GTSN with differing carbohydrate quantities or types. Methods: In two randomized, double-blind, crossover studies, participants (mean age 61 years) with type 2 diabetes consumed GTSN in a meal tolerance test. In the CHO Quantity Study, a standard nutritional beverage (STD) was compared to a low carbohydrate nutritional beverage with tapioca dextrin (GTSN-TDX) and a balanced carbohydrate nutritional beverage containing a blend of the slowly-digesting carbohydrates maltodextrin and sucromalt (GTSN-SDC). In the CHO Type Study, the GTSN beverages had similar carbohydrate quantities but varied in carbohydrate composition with GTSN-SDC compared to a formula with tapioca starch and fructose (GTSN-TS&F), and one with isomaltulose and resistant starch (GTSN-I&RS). Postprandial (0-240 min) concentrations of blood glucose, insulin (CHO Quantity Study only) and glucagon-like-peptide (GLP)-1 (CHO Quantity Study only) were measured. Results: Despite having substantially different carbohydrate quantities, the GTSN blunted the glucose positive area under the curve (AUC0-240 min) by 65% to 82% compared to the STD formulation (p < 0.001). GTSN also elicited ~50% lower insulin positive AUC0-240 min (p < 0.05), while postprandial GLP-1 responses were increased (p = 0.018) vs. STD. In the CHO Type Study, glucose positive AUC0-240 min tended to be lower for GTSN-SDC (1477 ± 460) than GTSN-TS&F (2203 ± 412;p = 0.062) and GTSN-I&RS (2190 ± 412;p = 0.076). No differences were observed between GTSN-TS&F and GTSN-I&RS. Conclusions: These results demonstrate the effectiveness of several GTSN products and suggest
