Insulin, encapsulation

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

FIGURE 10.4 Reduction in blood glucose following pulmonary administration of 1 U/kg insulin (a), insulin encapsulated in positively charged liposomes ( ), insulin encapsulated in negatively charged liposomes ( ), insulin encapsulated in neutral liposomes ( ). (Adapted from Li and Mitra 1996). 

Aboubakar, M. Puisieux, F. Couvreur, P. Deyme, M. Vauthier, C. Study of the mechanism of insulin encapsulation in poly(isobutylcyanoacrylate) nanocapsules obtained by interfacial polymerization. J. Biomed. Mater. Res. 1999, 47, 568-576. 

Sajeesh S, Bouchemal K, Marsaud V et al (2010) Cyclodextrin complexed insulin encapsulated hydrogel microparticles an oral delivery system for insulin. J Control Release 147(3) 377-384... 

Mesiha, M.S., Ponnapula, S., Plakogiannis, F. Oral absorption of insulin encapsulated in artificial chyles of bile salts, palmitic acid and a-tocopherol dispersions. Int. J. Pharm., 249,1, 2002. 

A -trimethylaininoethyl methacrylate chloride, respectively) enhanced the absorption and improved the bioavailabUity of insulin via the GI tract of normal male Sprague-Dawley rats to a greater extent than that of a phosphate-buffered solution of insulin. Increasing the surface charge of the nanoparticles improves insulin encapsulation efficiency and slows the release [144], The in vivo studies indicate that COM and CTM nanoparticles seem to be a very promising vehicle for oral administration of hydrophilic proteins and peptides. 

Insulin (molecular weight 7000) has been formulated in controlled release microbeads and pellets (135,136). A solvent evaporation micro-encapsulation procedure was used to produce microspheres with up to 20% by weight insulin. Solvent-casting techniques were used to prepare pellets. The investigations demonstrated that the PLA... 

Proteins may be stabilized by encapsulation in polyanhydride microspheres. Stability of proteins with respect to water-induced aggregation has been demonstrated to be a function of polymer hydrophobicity for insulin and bovine somatotropin as model proteins (Ron et al., 1993). Encapsulation and enzymatic activity of a variety of other proteins encapsulated in P(SA FAD) was studied by Tabata et al. (1993). 

Figure 3 presents an example of islet functioning inside a particular capsule. A typical two-phase perifusion profile is noted,similar in quantitative terms to that of unencapsulated islets. Clearly the ratio of the membrane thickness to capsule diameter is an important parameter, with low membrane capsule ratios providing rapid transfer of nutrients and the exodiffusion of insulin. Contrarily, for thick walled capsules of diameter less then approximately one-half millimeter the perifusion response, as measured by the stimulation index and retardation in insulin response to a glucose stimulus, is slower for encapsulated islets relative to free islets. 

Hydrogels are 3D cross-linked polymer networks. They can withstand acid conditions and release the entrapped drug molecules. Purdue University researchers have used a poly[methacrylic acid-g-poly(ethylene glycol)] hydrogel to encapsulate insulin, which could be released by pH trigger. 

Soon-Shiong P, Heintz RE, Merideth N, Yao QX, Yao ZW, Zheng TL, Murphy M, Moloney MK, Schmehl M, Harris M, Mendez R, Mendez R, Sandford PA. Insulin independence in a type-1 diabetic patient after encapsulated islet transplantation. Lancet 1994 343 950-951. 

By the use of a breath-powered unit dose dry powder inhaler, which was adapted to the physical properties of TI, relative bioavailability was 50% for the first 3 hours and 30% over the entire 6-hour period in 12 healthy volunteers (Pfutzner et al. 2002). However, although the studies demonstrated pulmonary administration of TI has the advantages of fast onset of action, short duration of action, and lower variability over the SC injections of insulin no attempt has been made to compare pulmonary administration of insulin alone with the same inhaler device. This method of encapsulating biomacromolecules has some advantages and must be considered when electing to deliver a molecule. 

Moreover, insulin-loaded PLA nanoparticles with high yields of encapsulation were produced by Elvassore and coworkers [61]. In this work, a homogeneous solution of protein and polymer is sprayed through a nozzle in a high-pressure vessel. In order to achieve nanoencapsulation, mixtures of dichloromethane (DCM) and dimethylsulfoxide (DMSO) were used to ensure the solubility of both the polymer and the protein. In Figure 9.9-3 a SEM image of the fine-particle powders produced is presented. 

Repeated episodes of catheter obstruction by fibrin clots or omental encapsulation can be a problem during continuous peritoneal insulin infusion from implanted pumps (SEDA 20, 397). In the encapsulated tissue, collagen fibrosis, inflammatory reactions with lymphocytes, and amyloid-like deposits reacting to anti-insulin antibodies can occur higher macrophage chemotaxis may also promote these processes. 

In an effort to develop an effective bioadhesive system for buccal administration, insulin was encapsulated into polyacrylamide nanoparticles by the emulsion solvent evaporation method [98]. Though nanoparticle formation ensures even distribution of the drug, pelleting of the nanoparticles was performed to obtain three-dimensional structural conformity. In addition, it was hypothetized that the pelletized particles will remain adhered to the mucosa, leading to good absorption. While studying bioadhesion and drug release profiles, it was found that the... 

---