In vitro and in vivo evaluation of a novel oral insulin formulation (original) (raw)
Related papers
Universal Journal of Pharmaceutical Research
The subcutaneous injection of insulin for the treatment of diabetes mellitus can lead to patient non-compliance, discomfort, pain and local infection is a chronic metabolic health disease affecting the homeostasis of blood sugar levels in human beings. Oral route of drug delivery system has been the most widely accepted means of drug administration other than invasive drug delivery systems. For the development of an oral insulin delivery system, we have to focus on overcoming the various gastro-intestinal barriers for insulin uptake from the gastrointestinal tract. To overcome these barriers various types of formulations such as insulin conjugates, micro/nanoparticles, liposomes, hydrogel, capsule, and tablets are designed to deliver insulin orally. Various potential ways to administer insulin orally has been explored over years but a fluctuating level of insulin release have been recorded. A number of advancement has taken place in the recent years for understanding the needs of im...
Journal of Pharmaceutical Sciences, 2016
Self-(nano)-emulsifying drug delivery systems (SNEDDSs) used to deliver peptides and proteins across biological barriers, such as the small intestinal membrane, represents an increasingly interesting field in nanomedicine. Hence, the present study was designed to evaluate the impact of SNEDDS on the transport and uptake mechanisms of insulin across the intestinal membrane. For this purpose, 3 SNEDDS were prepared, and Caco-2 cell monolayers were used to study transport and uptake. The prepared SNEDDSs were all in the range of 35-50 nm and had a negative zeta potential (between À8 and À25 mV). The entrapment of insulin on dispersion in the experimental media ranged from 40% to 78% for all SNEDDSs. Fluorescent microscopy studies indicated that fluorescein isothiocyanateelabeled insulin when administered in solution, as well as when loaded into MCT1 or MCT2 SNEDDS, localized within the intercellular space of the Caco-2 cell monolayer, indicating transport by paracellular diffusion. In contrast, the fluorescein isothiocyanateelabeled insulin in LCT SNEDDS was taken up by the cells. In conclusion, the present study demonstrated that MCT1 and MCT2 SNEDDS, but not LCT SNEDDS increased the transepithelial permeability of insulin, via the paracellular route.
Oral Insulin Delivery: Novel Strategies
2017
Diabetes is a disorder related to the deficiency in the secretion or action of insulin - a peptide hormone synthesized by the β cells of islets of pancreas. Insulin is given by the subcutaneous (SC) route. Patient non-compliance is frequent with the SC route. To remove the hurdle related to oral insulin delivery various efforts have been made. Thus, oral insulin is a dream of patients. Nanotechnology is an emerging era of science which provides an innovative means to detect, diagnose and to treat a disorder. Nanocarriers have been garnering more attention recently because of their size in nano range and greater surface area. These characteristics improve their absorption in contrast to bigger carriers. This article gives an insight into different novel approaches to get better oral insulin delivery. These novel formulations improve bioavailability; absorption problems associated with insulin and give protection from enzymatic degradation. More research has been done on nanoparticles...
Formulation and characterization of an oily-based system for oral delivery of insulin
European Journal of Pharmaceutics and Biopharmaceutics, 2009
The present work explored the possibility of formulating an oral insulin delivery system by combining the advantages of nanoencapsulation and the use of oily vehicle. The parameters affecting formulation such as association efficiency were characterized. The preparation was evaluated for its chemical, physical and biological stability. The preparation has unimodal particle size distribution with a mean diameter of 108 ± 9 nm. Insulin was protected from gastric enzymes by incorporation into lipid-based formulation. The results of RP HPLC and ELISA indicated that insulin was able to withstand the preparation procedure. Insulin in the preparations was stable for a period of one month at storage temperatures of 4 and 25°C. It was also biologically active and stable as demonstrated by the remarkable reduction of blood glucose levels of the STZ-diabetic rats after oral administration of the preparation. Moreover, hypoglycemic effect of nanoparticles administered orally was sustained for a longer period of time compared to the subcutaneous injection. These results clearly evidenced the ability of the nanoparticles to enhance the pharmacological response of insulin when given orally and could be used to deliver other peptides.
Oral Insulin Delivery: Unveiling Patented Approaches
Reviews in Advanced Sciences and Engineering, 2012
Oral route is the most commonly used, economical and convenient route of delivering drugs because no special skill is required for administering medications. Insulin is generally not delivered orally because of its proteinaceous nature due to which it undergoes inactivation by the acids and proteases of the gastrointestinal tract resulting in negligible oral bioavailability. Newer strategies are being explored for overcoming the problems associated with oral delivery of insulin. These include the use of permeation enhancers, protease inhibitors, enteric coatings and polymer microsphere formulations. These strategies aim at making insulin absorbable and bioavailable following oral administration. This article reviews the challenges and recently patented approaches in an endeavor to overcome the limitations associated with oral insulin delivery. She has published several research articles in the journals of international repute. Her research areas include sustained drug delivery and trans-dermal drug delivery.
Various Emerging Trends in Insulin Drug Delivery Systems
British Journal of Pharmaceutical Research, 2015
Lowering of blood glucose level in patients can be achieved by insulin therapy as it plays a key role in the control of hyperglycaemia for type 1 diabetes. Insulin delivery systems that are currently available include syringes, infusion pumps, jet injectors and pens. The tedious part for the type 1 diabetes patients is to tolerate needle after needle injections while undergoing treatment for both glucose measurement and to deliver insulin. A rigorous research effort has been undertaken worldwide to replace the authentic subcutaneous route by a more accurate and non-invasive route. The newer methods explored include the artificial pancreas with closed-loop system, transdermal insulin, and buccal, oral, pulmonary, nasal, ocular and rectal routes. The future trends include use of insulin inhalers, trandermal patches, pills, pumps etc. Some of the non-invasive delivery systems include polymeric hydrogels and insulin loaded bioadhesive poly(D,L-lactide-co-glycolide) nanoparticles for oral delivery, aerosolized liposomes with dipalmitoyl phosphatidylcholine for pulmonary delivery, β cyclodextrins for nasal delivery, microneedle arrays fabricated from hyaluronic acid and iontophoresis for trandermal delivery, chitosan-zinc-insulin complex for the controlled delivery of insulin.
Oral insulin delivery, existing barriers and current counter-strategies
Objectives The chronic and progressive nature of diabetes is usually associated with micro-and macrovascular complications where failure of pancreatic b-cell function and a general condition of hyperglycaemia is created. One possible fac-tor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the ratio-nale for oral insulin administration, existing barriers and some counter-strategies trialled. Key findings Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic b-cells from autoimmune destruction. Struc-tural modification, targeting a particular tissue/receptor, and the use of innova-tive pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal. Summary The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes.
Journal of Pharmacy and Pharmacology, 2002
We have recently succeeded in preparing insulin-loaded microcapsules that release the insulin in a strictly controlled manner with little initial rapid release in-vitro or in-vivo. We show here the superiority of the best formulation prepared with co-poly(D,L-lactic /glycolic) acids (PLGA) (mean MW 5800, L /G ratio 50: 50) with a main diameter of 15 C 30 m in-vivo. When 3.2% insulin-loaded PLGA microcapsules were subcutaneously given as a single dose to streptozotocin-induced hyperglycaemic rats (250 U kg 1 ), plasma insulin levels gradually increased and constant levels (30.3-94.1 U mL 1 ) were sustained. Rats receiving the formulation once a week showed not only steady plasma insulin levels, but also gained weight at a similar speed to normal rats. Meanwhile, daily treatment with Humulin U (25 U kg 1 ) caused a transient high insulin level (2723.9 U mL 1 at 1 h) in plasma, but the body weight of the rats was little changed. A pharmacological study in female Cynomolgus monkeys also revealed that the microcapsular formulation provided a at release of insulin for longer periods and showed no immunogenic activity. In the near future, therefore, this insulin formulation could become very bene cial as a provider of basal insulin levels for insulin-dependent diabetic patients.
Progress in Biomaterials
The objective of the present investigation was to formulate and characterize the human insulin entrapped Eudragit S100 microspheres containing protease inhibitors and to develop an optimized formulation with desirable features. A w/o/w multiple emulsion solvent evaporation technique was employed to produce microspheres of human insulin using Eudragit S-100 as coating material and polyvinyl alcohol as a stabilizer. The resultant microspheres were evaluated for drug-excipient compatibility, encapsulation efficiency, particle size, surface morphology, micromeritic properties, enteric nature, and in vitro drug release studies. Micromeritic properties indicated good flow properties and compressibility. In present investigation formulation F6 with drug/polymer ratio (1:100) was