Production, Properties and Swelling of Composite Agar-Pectic Gel Particles in an Artificial Gastroenteric Environment

The purpose of the present work was to obtain and study the properties of composite calcium-agar-pectic gel particles (CaAPGPs) obtained from aqueous solutions of agar (AA) and apple pectin (AP), from aqueous solutions of agar (AA) and pectin heracleuman (HS) in the presence of Ca2+ ions (0.34 M). The swelling of the obtained composite CaAPGPs in an artificial gastroenteric environment was also investigated. Methods and Results: We used commercial AP AU701 (AP, Herbstreith & Fox KG, Germany), HS isolated from the aerial part of the Sosnovskyi hogweed Heracleum sosnowskyi Manden, and food agar (AA). Spherical composite CaAPGPs were obtained from low-methyl esterified AP with a molecular weight of 406 kDa, pectin HS with a molecular weight >300 kDa, and food agar (AA) in the presence of Ca2+ ions (0.34 M) as a cross-linking agent by the method of ionotropic gelation. It was found that dry CaAPGPs based on AP (Ca-AA-AP) have a diameter of 1.16±0.14-1.23±0.05 mm, which was greater than the diameter of dry CaAPGPs based on HS (Ca-AA-HS) (0.95±0.12-1.16±0.05 mm). The density of dry CaAPGPs based on AP (Ca-AA-AP) with an increase in the concentration of AP in their composition from 1% to 2% increased by 1.7 times – from 0.37±0.07 mg/mm3 to 0.63±0.05 mg/mm3. Dry composite CaAPGPs based on HS (Ca-AA-HS) were denser. With an increase in the HS concentration in their composition from 1% to 2%, the degree of particle density increases by 2.2 – from 0.45±0.03 mg/mm3 to 0.97±0.19 mg/mm3. The swelling and degradation of the obtained dry composite CaAPGPs in an artificial gastroenteric environment were studied. It was found that CaAPGPs formed from 1% AP and 2% AA degraded almost immediately in SIF. Whereas, CaAPGPs formed from 2% AP and 1% or 2% AA completely degraded in SCF after 1 hour of incubation in it. CaAPGPs formed from 1% HS and 2% AA, and particles obtained from 2% HS and 1% AA, remained stable in SIF, and then completely degraded immediately upon entering in SCF. CaAPGPs, consisting of 2% HS and 2% AA, dissolve in SCF after 1 hour of incubation in it.

FORMULATION AND EVALUATION OF CAPTOPRIL BIOADHESIVE MICROSPHERES

In the present work, captopril microspheres using HPMCK100M, HPMCK15M and Carbopol 934 as copolymers were formulated by ionic cross linking technique (ionotropic gelation method) to deliver captopril via oral route. The technique was successfully employed to fabricate captopril microspheres and provides characteristic advantage over conventional microsphere method, which involves an “all-aqueous” system and thus avoids residual solvents in microspheres. Other methods utilize larger volume of organic solvents are costly and hazardous. Micromeritic studies revealed that the mean particle size was in the range of 512-903 μm. Increase in the polymer concentration led to increase in % yield, % drug entrapment effi ciency, particle size, % swelling and % mucoadhesion. The in vitro mucoadhesive study demonstrated that captopril microspheres using sodium alginate along with HPMCK100M as copolymer adhered to the mucus to a greater extent than the microspheres of captopril using albumin along with HPMCK15M and Carbopol 934 as copolymers.

Formulation and Characterization of Chitosan Based Dexibuprofen Nanoparticles Using Ionotropic Gelation Method

Dexibuprofen is a pharmacologically active enantiomer of racemic ibuprofen (NSAID), which is used to treat pain and inflammation. Like common NSAIDs, Dexibuprofen is an active enantiomer of ibuprofen that suppresses the prostanoid synthesis in the inflammatory cells via inhibition of the COX-2 isoform of the arachidonic acid COX. The therapeutic use of Dexibuprofen is limited by the rapidity of the onset of its action and its short biological half-life. Hence, our aim was to develop Dexibuprofen nanoparticles formulation to overcome these disadvantages using optimized concentration of polymers by appropriate methods for nanoparticle preparation. The drug and the nanoparticle formulation of Dexibuprofen F11 were comparatively assessed for FT IR spectrums by using FT-IR method. The DSC study was used as one of the tool to assess the compatibility between drug and the excipients. As per DSC thermograms, the drug as well as drug with mixture of excipients chitosan, sodium tripolyphosphate had shown no interactions with dexibuprofen. The ionotropic gelation method was used to prepare Dexibuprofen nanoparticles. The chitosan and sodium tripolyphosphate (TPP) of different concentrations were used as polymers to prepare Dexibuprofen nanoparticles. Total eleven different formulations were explored with different concentrations of drug : polymer ratios using ionotropic gelation method to identify optimal concentrations of polymer. Among different formulations, F11 formulation with optimized concentration of 5% chitosan and 1% Sodium tripolyphosphate polymers along with Dexibuprofen showed maximum drug release. The objective was to evaluate the developed Dexibuprofen nanoparticles. In-vitro drug release was evaluated in 0.05M phosphate buffer pH7.2 and found that the drug release of F11 formulation of Dexibuprofen nanoparticle had shown release till 24 hours more than that of other trials. Hence, F11 formulation was considered as the optimized nanoparticle formulation to control drug release till 24 hours. The entrapment efficacy of the formulated Nanoparticles was found to be in the range of 75.48%-91.22% respectively.

Palmarosa essential oil encapsulated in chitosan nanoparticles by ionotropic gelation: formulation and characterization

In this study, chitosan nanoparticles containing palmarosa essential oil (PEO-CNPs) were formed by ionotropic gelation, consisting of two parts: emulsion preparation followed by ionotropic gelation encapsulation with tripolyphosphate ions (TPP) as a crosslinker. The encapsulation method was optimized by varying three parameters, including chitosan concentration, initial oil loading in the emulsion and TPP concentration. The effects of these parameters on the encapsulation efficiency (EE) and loading capacity (LC) were analyzed. EE had an initial increase followed by a decrease in the range of three parameters. However, LC rose with varying initial oil content while it reduced with changing polymer and TPP concentration. The optimum experiment with the highest EE (10.0 g/L of chitosan, 5.0 g/L of TPP and 30.0 g/L PEO) was chosen to analyze the particle size using Dynamic Light Scanning method (DLS). With DLS measurement, the z-average diameter was 235.3 nm, and the particle size distribution was in the range of 100 – 500 nm.

Ionotropic Gelation-Based Synthesis of Chitosan-Metal Hybrid Nanoparticles Showing Combined Antimicrobial and Tissue Regenerative Activities

The treatment of skin wounds poses significant clinical challenges, including the risk of bacterial infection. In particular due to its antimicrobial and tissue regeneration abilities chitosan (a polymeric biomaterial obtained by the deacetylation of chitin) has received extensive attention for its effectiveness in promoting skin wound repair. On the other hand, due to their intrinsic characteristics, metal nanoparticles (e.g., silver (Ag), gold (Au) or iron oxide (Fe3O4)) have demonstrated therapeutic properties potentially useful in the field of skin care. Therefore, the combination of these two promising materials (chitosan plus metal oxide NPs) could permit the achievement of a promising nanohybrid with enhanced properties that could be applied in advanced skin treatment. In this work, we have optimized the synthesis protocol of chitosan/metal hybrid nanoparticles by means of a straightforward synthetic method, ionotropic gelation, which presents a wide set of advantages. The synthesized hybrid NPs have undergone to a full physicochemical characterization. After that, the in vitro antibacterial and tissue regenerative activities of the achieved hybrids have been assessed in comparison to their individual constituent. As result, we have demonstrated the synergistic antibacterial plus the tissue regeneration enhancement of these nanohybrids as a consequence of the fusion between chitosan and metallic nanoparticles, especially in the case of chitosan/Fe3O4 hybrid nanoparticles.

Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics

Microfluidics is emerging as a promising tool to control physicochemical properties of nanoparticles and to accelerate clinical translation. Indeed, microfluidic-based techniques offer more advantages in nanomedicine over batch processes, allowing fine-tuning of process parameters. In particular, the use of microfluidics to produce nanoparticles has paved the way for the development of nano-scaled structures for improved detection and treatment of several diseases. Here, ionotropic gelation is implemented in a custom-designed microfluidic chip to produce different nanoarchitectures based on chitosan-hyaluronic acid polymers. The selected biomaterials provide biocompatibility, biodegradability and non-toxic properties to the formulation, making it promising for nanomedicine applications. Furthermore, results show that morphological structures can be tuned through microfluidics by controlling the flow rates. Aside from the nanostructures, the ability to encapsulate gadolinium contrast agent for magnetic resonance imaging and a dye for optical imaging is demonstrated. In conclusion, the polymer nanoparticles here designed revealed the dual capability of enhancing the relaxometric properties of gadolinium by attaining Hydrodenticity and serving as a promising nanocarrier for multimodal imaging applications.

Thermoresponsive Chitosan-Grafted-Poly(N-Vinylcaprolactam) Microgels Via Ionotropic Gelation for Oncological Applications

Microgels can be considered soft, porous and deformable particles with an internal gel structure swollen by a solvent and an average size between 100 and 1000 nm. Due to their biocompatibility, colloidal stability, their unique dynamicity and the permeability of their architecture, they are emerging as important candidates for drug delivery systems, sensing and biocatalysis. In clinical applications, the research on responsive microgels is aimed at the development of “smart” delivery systems that undergo a critical change in conformation and size in reaction to a change in environmental conditions (temperature, magnetic fields, pH, concentration gradient). Recent achievements in biodegradable polymer fabrication have resulted in new appealing strategies, including the combination of synthetic and natural-origin polymers with inorganic nanoparticles, as well as the possibility of controlling drug release remotely. In this review, we provide a literature review on the use of dual and multi-responsive chitosan-grafted-poly-(N-vinylcaprolactam) (CP) microgels in drug delivery and oncological applications.