Gastric intrinsic factor: the gastric and small intestinal stages of cobalamin absorption. a personal journey.

Intrinsic factor (IF) was first identified as a component of the gastric mucosa that reacted with an extrinsic factor, later discovered to be vitamin B12 (VB12). IF has been extensively characterized, and its cloned cDNA used to produce sufficient IF to produce high quality antibodies, and to elucidate its 3-dimensional structure bound to cobalamin (Cbl, VB12). The absorption of the IF-Cbl complex involves internalization by endocytosis, incorporation into multivesicular/lysosomal bodies, release of Cbl by lysosomal proteolysis and pH effects, with subsequent binding to transcobalamin (TC).

Intestinal receptor targeting for peptide delivery: an expert's personal perspective on reasons for failure and new opportunities.

The technology has been available more than 25 years that would enable the oral delivery of vaccines, proteins and peptides, thus avoiding the need for injection. To this day, injection is still the mode of delivery, yet not the main mode of choice. This review focuses on several of the potential modes for oral delivery of peptides, proteins and vaccines.

The influence of molecular adjuvants in the cutaneous response to antigen after topical vaccination.

A micro-emulsion (ME), previously shown to enable topical delivery of therapeutic amounts of protein, was used for immunisation of multiple strains of mice with tetanus toxoid (TT). Topical vaccination with TT alone induced low levels of serum antibody in the BALB/c and A/J strains, with C57Bl/6 the only strain capable of a significant TT-specific antibody response. Topical vaccination with TT in combination with murabutide and monophosphoryl lipid A adjuvant generated high humoral and cellular responses in both C57Bl/6 and the non-responsive strain, BALB/c, comparable to intramuscular injection with TT adsorbed to Alum adjuvant.

Water-in-oil microemulsions for effective transdermal delivery of proteins.

Introduction: A water-in-oil microemulsion is a thermodynamically stable emulsion that has the capacity to 'hide' water-soluble molecules within a continuous oil phase. The very small size of the water droplets within the microemulsion means that these types of formulation can be applied topically to the skin, with the result that peptides and proteins can be delivered effectively into the dermal layer.

Areas Covered: This review discusses the general problems of peptide and protein delivery following topical application, and compares the possible routes of peptide and protein clearance and distribution within the body following topical administration.

Reduction in inflammation in the footpad of carrageenan treated mice following the topical administration of anti-TNF molecules formulated in a micro-emulsion.

Water-in-oil micro-emulsions (ME) have been shown to have the ability to deliver water-soluble peptides and proteins into the skin. Topical administration of these formulations represents an ideal means of device-free delivery of these pharmaceutical agents. Topically administered anti-tumor necrosis factor (TNF) monoclonal antibodies formulated within a water-in-oil micro-emulsion were found to have similar pharmaceutical activity to control formulations that were administered by injection.