Biodegradable nanoparticles for drug and gene delivery to cells and tissue

Oral strip technology: overview and future potential.

Thermal analysis and calorimetric methods in the characterisation of polymorphs and solvates

Attempts at replicating physiological insulin secretion, as a means of restoring the normal metabolic milieu and thereby minimizing the risk of diabetic complications, has become an essential feature of insulin treatment. However, despite advances in the production, purification, formulation and methods of delivery of insulin which have occurred in recent years, this has met with limited success. The current advocacy of intensive insulin therapy regimens involving multiple daily subcutaneous injection places a heavy burden of compliance on patients and has prompted interest in developing alternative, less invasive routes of delivery. To date, attempts to exploit the nasal, oral, gastrointestinal and transdermal routes have been mainly unsuccessful. The respiratory tree, with a large surface area, offers the greatest potential for the delivery of polypeptide drugs and there is renewed interest in administrating insulin by the intrapulmonary route. Current pulmonary drug delivery systems include a variety of pressurized metered dose inhalers, dry powder inhalers, nebulizers and aqueous mist inhalers. Recent clinical studies suggest a possible role for inhaled insulin in fulfilling meal-related insulin requirements in persons with Type 1 and Type 2 diabetes. Most experience with inhaled insulin has been obtained using either dry powder formulation in the Nektar Pulmonary Inhaler/Exubera device (Nektar Therapeutics Inc., San Carlos, CA, Aventis, Bridgewater, NJ, Pfizer, NY) or a liquid aerosol formulation in the AERx® Insulin Diabetes Management System (Aradigm Corp., Hayward, CA, NovoNordisk A/S, Copenhagen, Denmark). If long-term safety and efficacy is confirmed, inhalation may become the first non-subcutaneous route of insulin administration for widespread clinical use. Despite overwhelming interest and investment in administering insulin via the oral route, success is not expected in the short term. Attempts at utilizing the buccal mucosa and skin are also continuing. Pancreatic transplantation will remain limited to those patients receiving a kidney transplant and immunotherapy. Islet cell transplantation is at an early though encouraging stage following the availability of new less toxic immunosuppressive agents. True insulin independence will require further advances in the combined fields of cell biology and genetics to ensure freedom from both the need for lifelong administration of insulin and the complications of diabetes.

Alternative routes of insulin delivery

Insulin is essential for type 1 and advanced type 2 diabetics to maintain blood glucose levels and prolong lives. The traditional administration requires frequent subcutaneous insulin injections that are associated with poor patient compliance, including pain, local tissue necrosis, infection, and nerve damage. Taking advantage of emerging micro- and nanotechnologies, numerous alternative strategies integrated with chemical approaches for insulin delivery have been investigated. This review outlines recent developments in the controlled delivery of insulin, including oral, nasal, pulmonary, transdermal, subcutaneous and closed-loop insulin delivery. Perspectives from new materials, formulations and devices at the micro- or nano-scales are specifically surveyed. Advantages and limitations of current delivery methods, as well as future opportunities and challenges are also discussed.

Emerging micro- and nanotechnology based synthetic approaches for insulin delivery

Polymerized rosin: novel film forming polymer for drug delivery.

The present work was undertaken to study the effect of liposome formulation factors on its efficiency as a carrier for oral administration of insulin. The insulin-liposomes were prepared by two methods: solvent evaporation hydration and solvent spherule evaporation, with various variables such as concentration of insulin (I), lecithin (L), cholesterol (C), and Tween-80 (T). It was found that the insulin-liposomes when administered orally could produce hypoglycaemia. Variation in liposome composition was found to affect the efficiency of liposome as a carrier for oral administration of insulin. A liposome system containing L, 100 mg; C, 20 mg; I, 150 units; T, 1 per cent v/v, and prepared by the solvent spherule evaporation method was found to be most effective. The effect of insulin-liposome had prolonged action in diabetes-induced rabbits compared with that in normal rabbits. The results of the insulin-liposome system were comparable with the action of 1 unit of insulin/kg administered subcutaneously.

Liposomes as a carrier for oral administration of insulin: Effect of formulation factors

Two new rosin derivatives (RD-1 and RD-2) were synthesized in the laboratory and evaluated for physicochemical properties, molecular weight ( M w ), polydispersity ( M w / M n ) and glass transition temperature ( T g ). Plasticizer free films of the derivatives were produced by casting/solvent evaporation method. The surface morphology (SEM), water vapour transmission and mechanical properties (tensile strength, percent elongation and modulus of elasticity) of the films were investigated. The derivatives were further evaluated for pharmaceutical film coating by characterizing the release of a model drug (diclofenac sodium) from non-pariel seeds (pellets) coated with the derivatives. Pellet film coating could be achieved without agglomeration of the pellets within a reasonable operation time. Drug release from the coated pellets was sustained up to 10 h with the two rosin derivatives. These findings suggest the possible application of rosin derivatives (RD-1 and RD-2) for film coating.

A. K. Dorle

Papers

Polymerized rosin: novel film forming polymer for drug delivery.

Liposomes as a carrier for oral administration of insulin: Effect of formulation factors

Rosin derivatives: novel film forming materials for controlled drug delivery

Study of Rosin and Rosin esters as coating materials

Nanoparticles - a colloidal drug delivery system for primaquine and metronidazole.