Polyalkylcyanoacrylate or isobutylcyanoacrylate nano-capsules were used as a drug carrier also for oral administration [12, 13, 806-809] or enteral absorption  of insulin. The mechanism of formation of nanoparticles and nanocapsules of polyisobutyl-2-cyanoacrylate was studied . The absorption of insulin was studied by measuring fasting glycemia in streptozotocin-induced diabetic rats after a single administration of encapsulated insulin (100 units kg-1 ) at various sites along the gastrointestinal tract . The influence of sulfur dioxide and pH on the preparation and characterization of polyalkylcyanoacrylate nanoparticles was investigated . Oral administration of insulin incorporated into the wall of isobutylcyanoacrylate nanocapsule to diabetic rats induces a long-lasting normalization of their fasting glycemia. The biological action of encapsulated insulin on DNA and glycogen syntheses in Chinese hamster ovary cells transfected with the human insulin receptor gene was examined .
Nonobese diabetic mice develop an autoimmune disease with a long prodromal period and constitute a model for investigating the prevention of human type-1 diabetes. Since prophylactic insulin injections reduced the incidence of diabetes in nonobese diabetic mice, a prophylactic strategy was tested to prevent diabetes in nonobese diabetic mice consisting of oral administration of insulin, protected in polyalkylcyanoacrylate nanocapsules from degradation in the gastrointestinal tract . The early feeding with insulin nanocapsules reduced diabetes and insulitis in the nonobese diabetic mouse model that mimics human type-1 diabetes.
Biological activity of insulin immobilized in a polymer hydrogel modified with a proteolytic enzymes inhibitor was examined in in vitro and in vivo studies. Immobilization of insulin did not affect its biological activity. Oral administration of the immobilized insulin led to a reliably reduced
Nanocapsules concentration of glucose in the blood of test animals. The efficiency of the orally administered preparation amounted to 80% of the efficiency of hypodermally injected native insulin .
Physicochemical characterization of insulin-loaded poly-isobutylcyanoacrylate nanocapsules obtained by interfacial polymerization was carried out . The mechanism of insulin encapsulation and the type of interactions between the polymer forming the nanocapsule wall and the insulin were studied . These nanocapsules showed unexpected biological activity after intragastric administration [816, 817]. The hypoglycemic effect was characterized by a period of 2 days and a prolonged effect over a period of 20 days. Insulin was found unmodified during the nanoencapsulation process, due to the large amount of ethanol used in the preparation of the nanocapsules that initiated the polymerization of isobutylcyanoacrylate preserving the peptide from a reaction with the monomer. Results of the £ potential measurements showed that insulin was located inside the core of the nanocapsules and not simply adsorbed onto their surface.
Cyclodextrins and their hydrophilic derivatives were used as solubilizers capable of enhancing the loading capacity of liposomes and microparticles. Two possibilities of using cyclodextrins in the design of colloidal carriers were presented . The first possibility consists of increasing the loading capacity of polyisobutylcyanoacrylate nanospheres prepared by anionic polymerization, by employing hydroxypropyl cyclodextrins. The second possibility consists of the spontaneous formation of either nanocapsules or nanospheres by the nanoprecipitation of amphiphilic cyclodextrin diesters.
An improved method for the preparation of alkyl-cyanoacrylate nanocapsules was proposed that involved the intermediate synthesis of a well defined adduct of a single monomer unit to an ethanol molecule . It led to thinner capsule walls and, generally, to a more reproducible capsule structure. The chemical composition of the intermediate organic phase was studied by nuclear magnetic resonance spectroscopy. The morphology and size of resulting structures was analyzed, applying analytical ultracentrifuga-tion and light microscopic particle tracking. The sizes of capsules depended on the concentrations of the oil and the monomer components.
Alkylcyanoacrylates were polymerized anionically in water medium at different levels of pH. The effect of pH on the molecular weight and softening points of the polymers was studied . Alkylcyanoacrylates were polymerized in suspension by using the combination of methanol-water, and also by using different catalysts such as triethylamine, diazabicyclooctane, and diazabicycloundecane. The poly-cyanoacrylates were characterized by infrared and nuclear magnetic resonance spectroscopy. The molecular weight, molecular weight distribution, and the softening points of the polymers were determined.
The possibilities of sterilizing polybutylcyanoacrylate nanoparticle suspensions and lyophilized nanoparticle powders by autoclaving or formaldehyde treatment were evaluated . The nanoparticles were fabricated with different stabilizers. In most conditions a significant increase in particle size was determined after autoclaving of the nanoparticle suspensions and the nanoparticle powders were characterized by impaired resuspension characteristics.
Because poly(butyl a-cyanoacrylate) was less toxic than poly(isobutyl a-cyanoacrylate) and its nanocapsules could be orally absorbed via the intestine wall, polymeric nanocapsules as a drug delivery system of peptides were prepared by the interfacial polymerization of butyl a-cyanoacrylate . The aqueous phase contained a surfactant such as Tween 20 and polymeric stabilizer such as dextrin T-70, dextrin T-40, as well as Poloxamer 188. The organic phase was composed of monomer butyl a-cyanoacrylate and a cosol-vent such as glycerol trioleate or benzyl alcohol in bulky solvent ethanol or acetone.
A method for the determination of the cyclophosphamide content of polyalkylcyanoacrylate nanoparticles was developed . The analyses were carried out by inductively coupled plasma/atomic emission spectrometry (ICP/AES) by measuring the phosphorus content in the drug. The results obtained were compared with those given by high performance liquid chromatography that permits the detection of the cyclophosphamide molecule, and its degradation products.
The ileal uptake of polyalkylcyanoacrylate nanocapsules (less than 300 nm in diameter) was investigated in the rat . Iodized oil (Lipiodol) was used as the tracer for X-ray microprobe analysis in scanning electron microscopy. Polyalkylcyanoacrylate nanocapsules were able to pass through the ileal mucosa of the rat via a paracellular pathway in the nonfollicular epithelium and, most predominantly, via M cells and adjacent enterocytes in Peyer's patches.
The influence of several media (in vitro and ex vivo) present in the gastrointestinal tract on the stability of poly-isobutylcyanoacrylate nanoparticles was investigated . Polyisobutylcyanoacrylate nanoparticles were proven to be stable in a gastric environment and bioerodable in a simulated intestinal medium. Esterase caused a rapid degradation of the nanoparticles that was proportional to the amount of enzyme added to the medium.
The ability of polyisobutylcyanoacrylate nanocapsules was studied to protect insulin from degradation by proteolytic enzymes providing biologically active insulin by the oral route . Insulin was labeled with Texas Red for release studies and microscopy observations. Turbidimetric measurements and electron microscopy observations confirmed that the nanocapsules were degraded in the reconstituted intestinal medium, whereas nanocapsule integrity was preserved in the reconstituted gastric medium.
Doxorubicin-loaded polybutylcyanoacrylate (PBCA) nanoparticles were prepared by an emulsifier-free emulsion polymerization technique . The pH values of the polymerization medium and the weight ratios of doxorubicin to butylcyanoacrylate had a significant effect on the mean particle size. Drug loading and entrapment efficiency increased with increasing pH of the medium. Doxorubicin-loaded polybutylcyanoacrylate nanoparticles carried a positive charge, and the £ potential of drug-loaded nanoparticles increased with the increase of the polymerization pH. Figure 24 shows a TEM photograph of adriamycin-loaded polybutylcyanoacrylate nanoparticles .
The structure of gas-filled poly-[n-butyl-2-cyanoacrylate] (BCA) particles was demonstrated by negative staining with uranyl acetate, platinum-carbon shadowing of air-dried material, and thin sectioning of the aqueous suspension of BCA particles, embedded in water-soluble melamine resin . The polymer shell of the hollow particles possessed a globular outer surface and a smoother inner surface.
A copolymeric nanoparticulate drug delivery system (i.e., copolymerized peptide particles) was developed as a carrier for the oral uptake of therapeutic peptides , based on the copolymerization of the active peptide derivative with n-butylcyanoacrylate (n-BCA), the resulting copolymer being formulated as nanoparticles. The peptide luteiniz-ing hormone releasing hormone was used as a model drug to investigate the viability of the approach. The results demonstrated that chemical conjugation of a peptide within a protective particulate matrix was a viable approach for enhancing oral peptide delivery, presumably utilizing the gut-associated lymphoid tissue as a route delivery . The mechanism of uptake of biodegradable microparticles in Caco-2 cells was found to be microparticle diameter, concentration, and incubation time and temperature dependent . The small diameter microparticles (0.1 / m) had significantly greater uptake compared to larger diameter microparticles.
The potency of surface coating liposomes with some materials was investigated for oral delivery of peptide drugs . In vitro release of insulin, a model peptide, from liposomes in the bile salts solution was markedly reduced by coating the surface with the sugar chain portion of mucin or polyethyleneglycol. Encapsulation of insulin into mucin or polyethyleneglycol completely suppressed the degradation of insulin in the intestinal fluid, whereas uncoated liposomes suppressed it only partially. These results demonstrated that surface coating liposomes with polyethyleneglycol or mucin gained resistance against digestion by bile salts and increased the stability in the gastrointestinal tract.
Nanoparticles composed of new graft copolymers having a hydrophobic backbone and hydrophilic branches were prepared by the dispersion copolymerization of hydrophilic polyvinyl macromonomers with styrene in a polar solvent
. The potential of these nanoparticles as carriers for oral peptide delivery was investigated using salmon calcitonin in rats. The rate of salmon calcitonin incorporated in nanoparticles was high and was affected by the macromonomer structure. Anionic nanoparticles having poly(methacrylic acid) macromonomer chains on their surfaces showed the highest incorporating activity.
Biodegradable polymer membrane nanocapsules containing hemoglobin were prepared with phase separation and polymer precipitation methods using different polymers including polylactic acid and polyisobutylcyanoacrylate
. Preliminary in vivo tests showed that surface modified nanocapsules containing hemoglobin can survive longer in the circulation.
W/o/w multiple emulsions composed of medium-chain triglycerides containing insulin with aprotinin, a protease inhibitor, and/or sodium taurocholate, an absorption enhancer, were prepared by a two-step emulsification method at 15 °C . Whatever the nature of the substance introduced in the internal aqueous phase, all the emulsions obtained had very similar properties. The main release mechanism was a swelling-breakdown phenomenon after dilution of the emulsions under hypo-osmotic conditions. These emulsions were able to protect insulin against enzymatic degradation in vitro.
Poly(alkylcyanoacrylate) nanocapsules were used as biodegradable polymeric drug carriers for subcutaneous and peroral delivery of octreotide, a long-acting somatostatin analog. Their ability to reduce insulin secretion or prolactin secretion in response to oestrogens was studied in adult male rats .
In an ex vivo study, the absorption of cyclosporine A on bovine cornea after 24 h contact with various drug delivery systems containing 1% cyclosporine A was evaluated in comparison with an olive oil formulation as the reference vehicle for cyclosporine A . The different formulations studied were poly(acrylic acid) polymeric gels in aqueous/nonaqueous solvents, polyisobutylcyanoacrylate nanocapsules, and a combination of both formulations.
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All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.