Protamine nanocapsules as carriers for oral peptide delivery

The use of nanotechnologies to develop nanocarriers for oral insulin delivery is one of the strategies that has received significant attention. The basis for this development has been that nanocarriers can protect the peptides against the harsh gastric environment including enzymatic degradation, while controlling drug release and increasing their absorption in the small intestine. With a higher surface-to-volume ratio than that of conventional drug systems, nanocarriers can significantly increase their cellular contact with the intestinal epithelium, thereby offering more chances for the drug to get across this epithelium. The main aim of this work was to elucidate the potential of protamine nanocapsules as an effective oral drug delivery system for insulin (and other similar peptides). Nanocapsules consisting of an oily core and polymeric shell will be developed and characterized. Their stability in different simulated intestinal media with and without enzymes will be studied including their capacity to protect the loaded peptide from enzymatic degradation. Their toxicity and transport across Caco-2 cells will also be elucidated and thereafter their in vivo efficacy will be determined in rats

Preparation and characterization of alginate-chitosan nanoparticles as a drug delivery system for lipophilic compounds

M.Sc.Despite several decades of extensive research and development in pharmaceutical chemistry, the poor solubility of lipophilic compounds in aqueous media remains a major barrier to their absorption, bioavailability and clinical efficacy. This poor solubility is also a problem in other areas such as the flavour and fragrance industry. In cosmetics, for example, poor aqueous solubility and instability of oily compounds causes problems in formulation and fragrance stability. One approach to overcome these difficulties is to encapsulate oily compounds in biocompatible materials. As a drug delivery system such an approach is attractive if the size of the capsule is reduced to the micrometer or nanometer scale. Naturally occurring polysaccharides like sodium alginate (NaALG) and chitosan (CS) are generally regarded as safe (GRAS) for use in human use and have therefore gained much attention recently. As a drug delivery system, this polymer matrix can be used to prevent drug degradation in the gastro intestinal tract (GIT) and often provides controlled release of the encapsulant. Cyclodextrins (CDs) on the other hand offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent inclusion complexes with a range of organic compounds, and in so doing alter their physiochemical properties such as solubility. This study was aimed at exploring these concepts by using ALG and CS as an entrapment matrix for an essential oil, tagette oil (used as a model oily drug) that is insoluble in aqueous media. Alginate/chitosan (ALG/CS) nanoparticles were prepared in a 3-step procedure; emulsification of tagette oil in aqueous Na-ALG solution, followed by ionotropic pre-gelation of the ALG core with CaCl2 and further crosslinking with CS. Morphology and particle size measurements were performed by scanning and transmission electron microscopy (SEM and TEM), and Malvern Zetasizer

Nanotechnology-Based Diagnostics for Diseases Prevalent in Developing Countries: Current Advances in Point-of-Care Tests

The introduction of point-of-care testing (POCT) has revolutionized medical testing by allowing for simple tests to be conducted near the patient’s care point, rather than being confined to a medical laboratory. This has been especially beneficial for developing countries with limited infrastructure, where testing often involves sending specimens off-site and waiting for hours or days for results. However, the development of POCT devices has been challenging, with simplicity, accuracy, and cost-effectiveness being key factors in making these tests feasible. Nanotechnology has played a crucial role in achieving this goal, by not only making the tests possible but also masking their complexity. In this article, recent developments in POCT devices that benefit from nanotechnology are discussed. Microfluidics and lab-on-a-chip technologies are highlighted as major drivers of point-of-care testing, particularly in infectious disease diagnosis. These technologies enable various bioassays to be used at the point of care. The article also addresses the challenges faced by these technological advances and interesting future trends. The benefits of point-of-care testing are significant, especially in developing countries where medical care is shifting towards prevention, early detection, and managing chronic conditions. Infectious disease tests at the point of care in low-income countries can lead to prompt treatment, preventing infections from spreading

Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat

Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa