betadex and triphosphoric-acid

The main objective of the present study was to develop a nanoparticulate drug delivery system that can protect insulin against harsh conditions in the gastrointestinal (GI) tract. The effects of the following employed techniques, including lyophilisation, cross-linking and nanoencapsulation, on the physicochemical properties of the formulation were investigated.. We herein developed a nanocarrier via ionotropic gelation by using positively charged chitosan and negatively charged Dz13Scr. The lyophilised nanoparticles with optimal concentrations of tripolyphosphate (cross-linking agent) and β-cyclodextrin (stabilising agent) were characterised by using physical and cellular assays.. The addition of cryoprotectants (1% sucrose) in lyophilisation improved the stability of nanoparticles, enhanced the encapsulation efficiency, and ameliorated the pre-mature release of insulin at acidic pH. The developed lyophilised nanoparticles did not display any cytotoxic effects in C2C12 and HT-29 cells. Glucose consumption assays showed that the bioactivity of entrapped insulin was maintained post-incubation in the enzymatic medium.. Freeze-drying with appropriate cryoprotectant could conserve the physiochemical properties of the nanoparticles. The bioactivity of the entrapped insulin was maintained. The prepared nanoparticles could facilitate the permeation of insulin across the GI cell line.

Topics: Animals; beta-Cyclodextrins; Cell Line; Chemistry, Pharmaceutical; Chitosan; Cross-Linking Reagents; Drug Carriers; Drug Delivery Systems; Drug Liberation; Freeze Drying; Glucose; HT29 Cells; Humans; Hydrogen-Ion Concentration; Insulin; Mice; Myoblasts; Nanoparticles; Oligonucleotides; Polyphosphates

The aim of this study was to develop a novel controlled ionic gelation strategy for chitosan nanoparticle preparation to avoid particle aggregation tendency associated with conventional ionic gelation process. In this study inclusion complexation behaviour of sodium tripolyphosphate (TPP) with beta cyclodextrin (β-CD) has been investigated. The TPP-β-CD inclusion complex was characterized by FT-IR, XRD and DSC techniques. The complexation behaviour was also investigated by molecular docking study. The results showed that the TPP molecule formed inclusion complex with β-CD. Further, TPP-β-CD inclusion complex was used to prepare chitosan nanoparticles. The chitosan nanoparticles based on TPP-β-CD inclusion complex had smaller size of 104.2nm±0.608, good PDI value of 0.346±0.016 and acceptable zeta potential of +27.33mV±0.416. The surface characteristics of chitosan nanoparticles were also observed with transmission electron microscopy. Results indicates that TPP-β-CD inclusion complex can be used for the formation of chitosan nanoparticles with smaller and more uniform particle size in comparison to conventional TPP based chitosan nanoparticles.

Topics: beta-Cyclodextrins; Chitosan; Gels; Nanoparticles; Polyphosphates

Chitosan nanoparticles (CS-NPs) have been used to enhance the permeability of furosemide and ranitidine hydrochloride (ranitidine HCl) which were selected as candidates for two different biopharmaceutical drug classes having low permeability across Caco-2 cell monolayers. Drugs loaded CS-NPs were prepared by ionic gelation of CS and pentasodium tripolyphosphate (TPP) which added to the drugs inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-βCD). The stability constants for furosemide/HP-βCD and ranitidine HCl/HP-βCD were calculated as 335 M(-1) and 410 M(-1), whereas the association efficiencies (AE%) of the drugs/HP-βCD inclusion complexes with CS-NPs were determined to be 23.0 and 19.5%, respectively. Zetasizer and scanning electron microscopy (SEM) were used to characterise drugs/HP-βCD-NPs size and morphology. Transport of both nano and non-nano formulations of drugs/HP-βCD complexes across a Caco-2 cell monolayer was assessed and fitted to mathematical models. Furosemide/HP-βCD-NPs demonstrated transport kinetics best suited for the Higuchi model, whereas other drug formulations demonstrated power law transportation behaviour. Permeability experiments revealed that furosemide/HP-βCD and ranitidine HCl/HP-βCD nano formulations greatly induce the opening of tight junctions and enhance drug transition through Caco-2 monolayers.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Biological Transport; Caco-2 Cells; Chemistry, Pharmaceutical; Chitosan; Drug Carriers; Drug Compounding; Furosemide; Humans; Intestinal Absorption; Intestinal Mucosa; Kinetics; Microscopy, Electron, Scanning; Models, Biological; Nanoparticles; Nanotechnology; Particle Size; Permeability; Polyphosphates; Ranitidine; Solubility; Technology, Pharmaceutical; Tight Junctions

The aim of this study was to generate a new type of nanoparticles made of chitosan (CS) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) and to evaluate their potential for the association and delivery of macromolecular drugs. CS and CM-beta-CD or mixtures of CM-beta-CD/tripolyphosphate (TPP) were processed to nanoparticles via the ionotropic gelation technique. The resulting nanoparticles were in the size range of 231-383 nm and showed a positive zeta potential ranging from +20.6 to +39.7 mV. These nanoparticles were stable in simulated intestinal fluid pH 6.8 at 37 degrees C for at least 4h. Elemental analysis studies revealed the actual integration of CM-beta-CD to CS nanoparticles. Insulin and heparin used as macromolecular model drugs, could be incorporated into the different nanocarriers with association efficiencies of 85.5-93.3 and 69.3-70.6%, respectively. The association of these compounds led to an increase of the size of the nanoparticles (366-613 nm), with no significant modification of their zeta potentials (+23.3 to +37.1 mV). The release profiles of the associated macromolecules were highly dependent on the type of molecule and its interaction with the nanomatrix: insulin was very fast released (84-97% insulin within 15 min) whereas heparin remained highly associated to the nanoparticles for several hours (8.3-9.1% heparin within 8h). In summary, CS-CD (cyclodextrin) nanoparticles may be considered as nanocarriers for the fast or slow delivery of macromolecules.

Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Chitosan; Drug Carriers; Drug Compounding; Drug Stability; Heparin; Hydrogen-Ion Concentration; Insulin; Intestinal Secretions; Kinetics; Macromolecular Substances; Models, Molecular; Molecular Conformation; Nanoparticles; Particle Size; Polyphosphates; Solubility; Technology, Pharmaceutical