Solid lipid nanoparticles: Production, characterization and applications

Nanocapsule formation by interfacial polymer deposition following solvent displacement

Nanosilver: a nanoproduct in medical application.

Nanocarriers offer unique possibilities to overcome cellular barriers in order to improve the delivery of various drugs and drug candidates, including the promising therapeutic biomacromolecules (i.e., nucleic acids, proteins). There are various mechanisms of nanocarrier cell internalization that are dramatically influenced by nanoparticles' physicochemical properties. Depending on the cellular uptake and intracellular trafficking, different pharmacological applications may be considered. This review will discuss these opportunities, starting with the phagocytosis pathway, which, being increasingly well characterized and understood, has allowed several successes in the treatment of certain cancers and infectious diseases. On the other hand, the non-phagocytic pathways encompass various complicated mechanisms, such as clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis, which are more challenging to control for pharmaceutical drug delivery applications. Nevertheless, various strategies are being actively investigated in order to tailor nanocarriers able to deliver anticancer agents, nucleic acids, proteins and peptides for therapeutic applications by these non-phagocytic routes.

Nanocarriers’ entry into the cell: relevance to drug delivery

For the past few decades, there has been a considerable research interest in the area of drug delivery using particulate delivery systems as carriers for small and large molecules. Particulate systems like nanoparticles have been used as a physical approach to alter and improve the pharmacokinetic and pharmacodynamic properties of various types of drug molecules. They have been used in vivo to protect the drug entity in the systemic circulation, restrict access of the drug to the chosen sites and to deliver the drug at a controlled and sustained rate to the site of action. Various polymers have been used in the formulation of nanoparticles for drug delivery research to increase therapeutic benefit, while minimizing side effects. Here, we review various aspects of nanoparticle formulation, characterization, effect of their characteristics and their applications in delivery of drug molecules and therapeutic genes.

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Nanoparticles - A Review

Polyalkylcyanoacrylate nanocapsules (mean size 220 nm), composed of spheric polymeric structures, have been used as a drug carrier for insulin. The rate of encapsulation of insulin is 54.9%, and we studied the therapeutic efficiency of the nanocapsules in diabetic and normal rats. When administered subcutaneously, insulin-loaded nanocapsules prolonged the hypoglycemic effect of insulin; the duration of this effect increased with the doses. When administered orally by force-feeding to diabetic rats, insulin nanocapsules (12.5, 25, and 50 U/kg) decreased fasted glycemia 50-60% by day 2. This effect was maintained for 6 or 20 days with 12.5 or 50 U/kg, respectively. Only the dose of 100 U/kg decreased fed glycemia by 25% in diabetic rats. In normal rats, hyperglycemia induced by an oral glucose load was reduced by 50% with the same dose of oral insulin nanocapsules. We concluded that polyalkylcyanoacrylate nanocapsules preserve the therapeutic effect of insulin when administered orally and prolong this effect when administered subcutaneously and orally.

New Approach for Oral Administration of Insulin With Polyalkylcyanoacrylate Nanocapsules as Drug Carrier

Nanocapsules as carriers for oral peptide delivery

Transmucosal passage of polyalkylcyanoacrylate nanocapsules as a new drug carrier in the small intestine.

Isobutylcyanoacrylate nanocapsules have been used as drug carriers for the enteral absorption of insulin. Their absorption has been studied by measuring fasted glycaemia in streptozotocin-induced diabetic rats after a single administration of encapsulated insulin (100 units kg-1) at various sites along the gastrointestinal tract. Glycaemia decreased from the second day, the intensity and duration depending on the site of administration (65% ileum, 59% stomach, 52% duodenum and jejunum, 34% colon). This hypoglycaemic effect lasted up to the 18th day after administration for ileum and jejunum, the 15th day for stomach and duodenum, and the 13th day for colon. In-vitro, nanocapsules protect insulin against proteolysis from pepsin, chymotrypsin and trypsin. These results suggest (i) that insulin is protected by nanocapsules in the gastrointestinal tract, (ii) that it is absorbed in an active form, and (iii) that ileum is the most potent site of absorption.

The effect of site of administration in the gastrointestinal tract on the absorption of insulin from nanocapsules in diabetic rats.

It has been shown that insulin associated with nanocapsules of isobutylcyanoacrylate retains biological activity after oral administration to diabetic rats from 6 to 21 days. Because part of this action is unexplained, we focused on the interaction of encapsulated insulin with the insulin receptor in vitro. We have shown that encapsulated insulin is able 1) to bind to insulin receptors both in rat liver plasma membranes and after solubilization from Chinese hamster ovary (CHO) cells transfected with the gene of human insulin receptor, 2) to accelerate 125I-labeled insulin dissociation from its receptor, and 3) to ensure transduction of a signal leading to stimulation of the β-subunit phosphorylation, with parameters similar to those of native insulin. In addition, encapsulated 125I-insulin was rapidly internalized in transfected CHO cells. Analysis of cell-associated radioactivity showed that encapsulated insulin remained largely intact (> 80%) after 3 h, whereas native insulin was mostly degraded. These data indicate that encapsulated insulin fulfills all the earliest events at the receptor level leading to biological actions and suggests that encapsulation protects insulin against insulin degradation inside the cells.

C. Michel

Papers

New Approach for Oral Administration of Insulin With Polyalkylcyanoacrylate Nanocapsules as Drug Carrier

Nanocapsules as carriers for oral peptide delivery

Transmucosal passage of polyalkylcyanoacrylate nanocapsules as a new drug carrier in the small intestine.

The effect of site of administration in the gastrointestinal tract on the absorption of insulin from nanocapsules in diabetic rats.

Encapsulation of Insulin for Oral Administration Preserves Interaction of the Hormone with Its Receptor In Vitro