Effective Oral Delivery System Research Articles

Enhanced storage and gastrointestinal stability of spray-dried whey protein emulsions with chitosan and gum Arabic.

Protein-based emulsions are widely utilized for delivering bioactives but suffer from thermodynamic instability, microbial spoilage, and gastrointestinal instability, necessitating enhancement strategies. This study explores the improvement of whey protein isolate (WPI) emulsions through chitosan (CS) coating and spray drying with maltodextrin (MD) or gum Arabic (GA). Canola oil droplets were stabilized with WPI, electrostatic coated with CS, and spray-dried. CS addition significantly increased entrapment efficiency from ∼75-78% to ∼95-98%, correlating with enhanced storage and gastrointestinal stability. During a 2-h gastric digestion study, CS/GA-protected powders demonstrated only 3.6% lipolysis compared to 27.1% for unprotected WPI emulsions, exhibiting superior gastric resistance. Under small intestinal conditions, their digestion rate constant was one-fifth of that for unprotected WPI emulsions. Furthermore, CS/GA-protected powders maintained excellent storage stability for one year. These findings highlight the potential of WPI-based emulsion powders as effective oral delivery systems for lipophilic bioactives, offering improved storage and gastrointestinal stability.

Enhanced Gut-to-Liver Oral Drug Delivery via Ligand-Modified Nanoparticles by Attenuating Protein Corona Adsorption.

The development of effective oral drug delivery systems for targeted gut-to-liver transport remains a significant challenge due to the multiple biological barriers including the harsh gastrointestinal tract (GIT) environment and the complex protein corona (PC) formation. In this study, we developed ligand-modified nanoparticles (NPs) that enable gut-to-liver drug delivery by crossing the GIT and attenuating PC formation. Specifically, mesoporous silica nanoparticles (MSNs) were functionalized with peptides targeting the neonatal Fc receptor (FcRn), capitalizing on FcRn expression in the small intestine and liver for targeted drug delivery. We showed that MSNs decorated with a small cyclic FcRn binding peptide (MSNs-FcBP) obtained enhanced diffusion in intestinal mucus and superior transportation across the intestine compared to unmodified MSNs and MSNs decorated with a large IgG Fc fragment (MSNs-Fc), which correlated with diminished protein adsorption and weaker interaction with mucin. After entering the blood circulation, reduced serum PC formation by MSNs-FcBP reduces the proteolytic and phagocytic propensity of the reticuloendothelial system, ultimately ameliorating accumulation in hepatocytes. Pharmacokinetic and pharmacodynamic studies in diabetic mice revealed that MSNs-FcBP effectively transported the therapeutic agent exenatide across the intestinal epithelium, leading to a significant hypoglycemic response and improved glucose tolerance. This study underscores the critical role of ligand selection in limiting protein corona formation, thereby significantly enhancing gut-to-liver drug delivery by increasing mucus permeation and minimizing serum-protein interactions. The effective delivery of exenatide in diabetic mice illustrates the potential of this strategy to optimize oral drug bioavailability and therapeutic efficacy.

Development of inulin nanocarrier for effective oral delivery of insulin: synthesize, optimization, characterization, and biophysical study

The susceptibility of insulin against gastric acid degradation presents a major challenge for oral insulin delivery. The potential of biopolymer-based nanocarriers was investigated in order to address this issue. Inulin, a biopolymer produced by the halophilic bacterium Salinivibrio sp. GM01, has been evaluated for its effectiveness as an insulin nanocarrier. Using central composite design (CCD) method, the optimum condition of inulin-encapsulated insulin (I-In) was achieved at 53 mg of inulin stirred at 17,800 rpm for 10 min, resulting in spherical I-In nanoparticles (I-In NPs) with an average diameter of 416 ± 32 nm and encapsulation efficiency of 87.04 ± 3.01%. The insulin release profile of I-In NPs in simulated gastric fluid follows a burst pattern. Biophysical analysis revealed that insulin in I-In NPs had higher conformational stability than the free state (FS) insulin, as evidenced by an increase in denaturation half-life up to 60 min and the transition enthalpy by 0.29 and 1.53 kcal/mol for secondary and tertiary structures, respectively. Furthermore, preliminary in vivo studies showed that I-In NPs showed significant effect compared to FS insulin for up to 15% in blood glucose level reduction. This study demonstrates the potential of I-In NPs as a promising candidate for antidiabetic therapy and an effective oral delivery system.

Thymoquinone Pectin Beads Produced via Electrospray: Enhancing Oral Targeted Delivery for Colorectal Cancer Therapy.

Background/Objectives: Thymoquinone (TQ) exhibits diverse biological activities, but its poor solubility and bioavailability limit its cancer efficacy, requiring innovative solutions. This study explores the development of an oral delivery system targeting colon cancer based on TQ pectin beads (TQ-PBs) produced through an adjustable electrospray technique. This study hypothesised that adjusting bead diameter through the electrospray technique enables precise control over water absorption and erosion rates, thereby achieving a controlled release profile for encapsulated TQ, which enhances targeted delivery to the colon. Methods: TQ-PBs were synthesised and optimised using an electrospray technique based on the ionic gelation method. The prepared beads were characterised based on particle size, sphericity, encapsulation efficiency (EE), water uptake, erosion, surface morphology, molecular interactions, and texture. The cumulative TQ release studies, an accelerated stability test, and cytotoxicity evaluation against the colon cancer HT-29 cell line were also assessed. Results: The optimised TQ-PB formulation demonstrated an average bead size of 2.05 ± 0.14 mm, a sphericity of 0.96 ± 0.05, and an EE of 90.32 ± 1.04%. The water uptake was 287.55 ± 10.14% in simulated gastric fluid (SGF), 462.15 ± 12.73% in simulated intestinal fluid (SIF), and 772.41 ± 13.03% in simulated colonic fluid (SCF), with an erosion rate of 45.23 ± 5.22%. TQ release was minimal in SGF (8.13 ± 1.94% after 2 h), controlled in SIF (29.35 ± 3.65% after 4 h), and accelerated in SCF (94.43 ± 2.4% after 3 h). Stability studies over one month showed a size reduction of 17.50% and a 6.59% decrease in TQ content. Cytotoxicity assessments revealed significant anticancer activity of TQ-PB, with an IC50 of 80.59 ± 2.2 μg/mL. Conclusions: These findings underscore the potential of TQ-PB as an effective oral drug delivery system for targeted colorectal cancer therapy.

Biodegradable polymeric nanocomposite containing phloretin for enhanced oral bioavailability and improved myocardial ischaemic recovery

Aim The study aimed to enhance phloretin’s oral absorption and systemic availability through nanoencapsulation within biodegradable polymers, improving its anti-oxidant and cardioprotective potential. Methods Phloretin-loaded polymeric nanocomposites were prepared using ionic gelation and optimised for yield, encapsulation, loading, particle size, PdI and zeta potential. The formulation was characterised by FTIR, XRD, FESEM and MS. In-vitro drug release, stability, pharmacokinetics, biodistribution, anti-oxidant capacity, haemolysis and both in-vitro and in-vivo assessments were conducted in an ischaemia-induced rat model. Results The average particle size, zeta potential, encapsulation and drug loading of the optimised nanoparticles were 105.8 ± 1.92 nm, −41.5 ± 1.10 mV, 92.36 ± 0.01% and 18.47 ± 0.38%, respectively. Nano-phloretin enhanced oral bioavailability, anti-oxidant capacity. In-vivo, it reduced myocardial infarct size by ∼46% versus ∼13% for free phloretin, showing significant cardiomyocyte protection and ROS suppression. Conclusion The study demonstrates polymer-based nanoparticles as effective oral drug delivery systems capable of enhancing both systemic bioavailability and therapeutic efficacy of the encapsulated drug.

Biomolecular Condensates Based on Amino Acid for Enhancing Oral Bioavailability and Therapeutic Efficacy of Hydrophobic Drugs.

The oral administration of chemo- or immunotherapeutic drugs presents a compelling alternative for patients with malignant colorectal cancer, offering a convenient and patient-compliant "hospital-free" strategy. Unfortunately, the hydrophobic nature of many drug candidates, alongside the harsh conditions of the gastrointestinal tract, frequently results in suboptimal bioavailability and heightened systemic toxicity. To address these challenges, we harnessed the unique properties of biomolecular condensates, which form through a liquid-liquid phase separation mechanism, to develop a versatile platform for drug encapsulation and delivery. In this study, we introduce a reliable and effective amorphous oral drug delivery system based on biomolecular condensates derived from the amino acid derivative N-(benzyloxycarbonyl)-l-proline (ZP). These ZP condensates exhibit dynamic intermolecular interactions and possess unique physicochemical attributes such as fluidity and viscoelasticity. They significantly improve the solubility of hydrophobic drugs, ensuring enhanced stability and optimized pharmacokinetics under physiological and gastrointestinal conditions. By maintaining drugs in an amorphous state, we substantially increased drug bioavailability and markedly improved pharmacokinetics. Furthermore, the ZP condensates demonstrate potential as an integrated therapeutic platform capable of potentiating the synergies between chemotherapy and immunotherapy while concurrently reducing systemic toxicity. This has resulted in a significant enhancement of chemo-immunotherapy efficacy in the treatment of colorectal cancer, representing a notable advancement in drug delivery and oncology.

Polycaprolactone-Vitamin E TPGS Micellar Formulation for Oral Delivery of Paclitaxel.

This study aimed to investigate the potential of polycaprolactone-vitamin E TPGS (PCL-TPGS) micelles as a delivery system for oral administration of paclitaxel (PTX). The PCL-TPGS copolymer was synthesized using ring opening polymerization, and PTX-loaded PCL-TPGS micelles (PTX micelles) were prepared via a co-solvent evaporation method. Characterization of these micelles included measurements of size, polydispersity, and encapsulation efficiency. The cellular uptake of PTX micelles was evaluated in Caco-2 cells using rhodamine 123 (Rh123) as a fluorescent probe. Moreover, an everted rat sac study was conducted to evaluate the ex vivo permeability of PTX micelles. Additionally, a comparative pharmacokinetic study of PTX micelles versus the marketed formulation, Ebetaxel® (a Taxol generic), was performed after a single oral administration to rats. The results demonstrated that the micellar formulation significantly improved PTX solubility (nearly 1 mg/mL). The in vitro stability and release of PTX micelles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) demonstrated that PTX micelles remained stable for up to 24 h and significantly slowed the release of PTX in both media compared to Ebetaxel®. The in vitro cellular uptake, ex vivo intestinal permeability, and in vivo pharmacokinetic profile demonstrated that PTX micelles enhanced the permeability and facilitated a rapid absorption of the drug. Conclusively, the PCL7000-TPGS3500 micelles exhibit potential as an effective oral delivery system for PTX.

Enhancing solubility and oral bioavailability of rosuvastatin through interpenetrating polymer network (IPN) nanogels: Fabrication, characterization, and in-vivo efficacy assessment

Rosuvastatin (RST) exhibits low aqueous solubility, presenting a challenge for its effective oral administration. The objective of this study is to improve the solubility of RST through the creation and assessment of interpenetrating polymer network (IPN) nanogels. The nanogels were produced via a free radical polymerization method, where hydrophilic polymers β-cyclodextrin (β-CD) and Poloxamer-407 (P407) were combined with the monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS). Comprehensive characterization of the nanogels included drug loading efficiency, solubility studies, zeta sizer measurements, sol-gel analysis, Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), swelling studies, and in-vitro release analysis. Oral toxicity experiments were performed to verify the safety of the β-CD/Poloxamer-407-co-poly (AMPS) IPN nanogels when taken by mouth. The scanning electron microscopy (SEM) investigation unveiled a network structure characterised by porosity and sponginess. The thermal stability and complex synthesis of the nanogel components were validated by the FTIR, TGA, and DSC spectra. X-ray diffraction (XRD) analysis indicated a reduction in the crystallinity of RST within the nanogel matrices. The optimized nanogels formulation demonstrated a particle size of 185.71 ± 1.03 nm. Comparative studies with a reference product highlighted significant enhancements in drug solubility and release characteristics attributed to the fabricated nanogels. Toxicity assessments confirmed the non-toxic nature of the nanogels, supporting their biocompatibility. In-vivo studies using hyperlipidemic animal models validated the anti-hyperlipidemic efficacy of the developed nanogels. The nanogels' biocompatibility, high solubilization capacity, improved dissolution profile, rapid production process, and superior physicochemical properties underscore their potential as an effective oral delivery system for lipophilic drugs.

Multi-functional Chitosan Polymeric Micelles for improving the oral bioavailability of Paclitaxel based on synergistic effect.

A novel multi-functional micelle delivery system was developed for enhancing the oral absorption of paclitaxel (PTX). The delivery carriers were constructed by modifying chitosan-stearic acid (CS-SA) micelles with L-carnitine (LC) and co-encapsulating quercetin (Que), and the PTX-loaded micelles were prepared by film-sonication dispersing technique. The as-prepared micelles showed homogeneous spherical shapes with a small particle size of 148.3 ± 1.7nm, high drug loading of 7.05% and low critical micelle concentration (CMC) of 16.89µg/ml. Compared to the in-house PTX formulation similar to the commercial injection Taxol™, the target PTX-loaded micelles had obvious sustained-release effects and exhibited an oral relative bioavailability of 168.08%. The cellular uptake studies of Caco-2 cells confirmed the micellar modification of LC and the co-loading of Que played important roles in promoting the absorption of drug loaded in micelles. The CYP3A4 enzyme test demonstrated the micelles had an inhibitory effect on the metabolic enzyme due to the presence of Que. These findings confirmed the potential of the multi-functional chitosan polymeric micelles based on synergistic effect as an effective oral delivery system.

Amphiphilic, lauric acid-coupled pluronic-based nano-micellar system for efficient glipizide delivery

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of −17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

PREPARATION AND EVALUATION OF MELOXICAM CHEWABLE TABLETS FOR BETTER ORAL DELIVERY

In the current study, meloxicam (MXM) chewable tablets were formulated and evaluated with an aim of improving its solubility, bioavailability and masking its bitter taste in order to create an effective oral drug delivery system. Meloxicam (BCS class II drug), non steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties, acts by inhibition of prostaglandin synthetase leading to inhibition of prostaglandin synthesis. MXM chewable tablets were made by three different techniques: AG (aqueous granulation), NAG (non-aqueous granulation) and DC (direct compression). The chewable tablets of MXM so prepared were assessed for various parameters, namely, palatability test, hardness, weight variation, mechanical strength, disintegration, friability, percent assay and in vitro testing for dissolution profile. The variation found in dissolution profile for all prepared batches was in the order: DC&gt;NAG&gt;AG. The percent assay was found within the range (90-110%). Observations from palatability study showed good overall tolerance levels for DC and AG and moderate tolerance levels for NAG.

An M cell-targeting recombinant L. lactis vaccine against four H. pylori adhesins

The acidic environment and enzyme degradation lead to oral vaccines often having little immune effect. Therefore, it is an attractive strategy to study an effective and safe oral vaccine delivery system that can promote gastrointestinal mucosal immune responses and inhibit antigen degradation. Moreover, the antigens uptake by microfold cells (M cells) is the determining step in initiating efficient immune responses. Therefore, M cell-targeting is one promising approach for enhancing oral vaccine potency. In the present study, an M cell-targeting L. lactis surface display system (plSAM) was built to favor the multivalent epitope vaccine antigen (FAdE) to achieve effective gastrointestinal mucosal immunity against Helicobacter pylori. Therefore, a recombinant Lactococcus lactic acid vaccine (LL-plSAM-FAdE) was successfully prepared, and its immunological properties and protective efficacy were analyzed. The results showed that LL-plSAM-FAdE can secretively express the recombinant proteins SAM-FAdE and display the SAM-FAdE on the bacterial cell surface. More importantly, LL-plSAM-FAdE effectively promoted the phagocytosis and transport of vaccine antigen by M cells in the gastrointestinal tract of mice, and simulated high levels of cellular and humoral immune responses against four key H. pylori adhesins (Urease, CagL, HpaA, and Lpp20) in the gastrointestinal tract, thus enabling effective prevention of H. pylori infection and to some extent eliminating H. pylori already present in the gastrointestinal tract.Key points• M-cell-targeting L. lactis surface display system LL- plSAM was designed• This system displays H. pylori vaccine-promoted phagocytosis and transport of M cell• A promising vaccine candidate for controlling H. pylori infection was verified

P116 Gastro-resistant microparticles for the oral delivery of Phycocyanin in the Inflammatory Bowel Disease therapy

Abstract Background Inflammatory Bowel Disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, with ambiguous etiology. Oral route is the most common and acceptable approach for drug administration in the IBD treatment. However, it remains a challenge to maintain the stability of the drugs during oral treatment, particularly in the gastric environment, due its harsh conditions. In this context, the antioxidant and antiinflagmmatory properties of various natural compounds, as Phycocyanin (PC), a water-soluble bioactive molecule found in algae, can be strongly affected by factors as pH and temperature, inducing PC degradation and attenuating the curative effects. In this work, we produced a gastro-resistant microparticles (MPs) as controlled release systems for PC, and we aimed to compare its efficacy with free PC effects, on rat model of IBD. Methods The novel pharmaceutical system (SPC) was produced by microencapsulation technique, the spray-drying technique, using soy proteins (SPs) as natural excipients, aiming to improve the stability of the active ingredient and to ensure a modified release profile of PC. Rats were divided into groups and colitis was induced by intracolonic instillation of Dinitrobenzene sulfonic acid (DNBS, 20 mg/rat). Effects of preventive oral treatment of free PC or SPC were investigated, bioavailability was assessed and then body weight loss, stool consistency, colon weight/length index, myeloperoxidase activity (MPO), macroscopic damage and disease activity index (DAI) were determined. Results The SPC microparticle systems showed enhanced bioavailability of Phycocyanin, resulting in increased blood concentrations. The SPC system achieved the maximum AUC value and a modified release profile, particularly for gastro-resistant types, with a delayed Tmax of 5 hours, indicating their potential as a gastro-resistant formulation. Both PC and SPC pretreatments significantly ameliorated the severity of DNBS-induced colitis, however SPC pretreatment demonstrated enhanced activity vs PC. SPC rats showed a reduction of DAI, body weight loss and diarrhea incidence &amp;gt;15%, compared to PC (P&amp;lt;0.05); the ability of preventing the DNBS-induced macroscopic colonic damage and the MPO increase in SPC group were significantly higher than PC group (P&amp;lt;0.05) and also a tendency to improvement of colon weight/length index was observed. Conclusion In conclusion, the results of our research demonstrated that gastro-resistant microparticles (SPC) exhibit significantly improved therapeutic efficacy compared to orally administered free PC and can be developed as an effective new oral drug delivery system with controlled release profile in the treatment of IBD.

Novel chitosan and N-isopropylacrylamide-grafted-dextran-based microformulations as effective oral drug delivery system

Novel chitosan and N-isopropylacrylamide-grafted-dextran-based microformulations as effective oral drug delivery system

Use of novel taurine-chitosan mediated liposomes for enhancing the oral absorption of doxorubicin via the TAUT transporter

Our research aimed to enhance the oral bioavailability of doxorubicin hydrochloride (DOX·HCl) while minimizing the potential for myocardial toxicity. To achieve this goal, we developed a new method that utilizes a coating material to encapsulate the drug in liposomes, which can specifically target intestinal taurine transporter proteins. This coating material, TAU-CS, was created by combining taurine with chitosan. We characterized TAU-CS using various methods, including 1H NMR, FT-IR, and scanning electron microscopy (SEM). The resulting liposomes exhibited a regular spherical morphology, with a particle size of 195.7 nm, an encapsulation efficiency of 91.23 %, and a zeta potential of +11.65 mV. Under simulated gastrointestinal conditions, TAU-CS/LIP@DOX·HCl exhibited good stability and slow release. Pharmacokinetic studies revealed that, compared with DOX·HCl, TAU-CS/LIP@DOX·HCl had a relative bioavailability of 342 %. Intracellular uptake, immunofluorescence imaging, and permeation assays confirmed that the taurine transporter protein mediates the intestinal uptake of these liposomes. Our study suggested that liposomes coated with TAU-CS could serve as an effective oral delivery system and that targeting the taurine transporter protein shows promise in enhancing drug absorption.

Natural Coptidis Rhizoma Nanoparticles Improved the Oral Delivery of Docetaxel.

Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract. DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX's shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines. Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of -20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells. The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.

Preparation, in vitro and in vivo evaluation of a novel mitiglinide microemulsions

This study aimed to prepare an o/w mitiglinide microemulsion (MTGME) to improve the drug solubility and bioavailability. The formulation of o/w MTGME was optimized by the solubility study of drug, pseudo-ternary phase diagram and Box-Behnken design successively. MTGME was characterized by dynamic laser light scattering (DLS), zeta potential and transmission electron microscopy (TEM), moreover, the storage stability, pharmacodynamics and pharmacokinetics were investigated. The optimal prescription for MTGME consisted of Maisine 35–1 (oil), Cremophor EL (surfactant) and propylene glycol (PG, cosurfactant). MTGME with a spherical dimension of 58.1 ± 5.86 nm was stable when stored at 4 °C for 3 months. The blood glucose levers (BGL) of diabetic mice were uniformly and significantly decreased by intragastric (i.g.) administration of 1–4 mg/kg MTGME, in which BGL (i.g. 4 mg/kg MTGME) was reduced by 69% during 24 h. The pharmacokinetics study of MTGME (i.g., 20 mg/kg) in Wistar rats showed higher plasma drug concentration (Cmax, 2.9 folds), larger area under curve (AUC, 4.6 folds) and oral bioavailability than those of MTG suspensions. Generally, the MTGME (o/w) showed good effect on controlling hyperglycemia. Therefore, microemulsion can be used as an effective oral drug delivery system to improve the bioavailability of MTG.

Formulation of Chitosan-Zein Nano-in-Microparticles for Oral DNA Delivery.

Gene delivery via the oral route offers a promising strategy for improving DNA vaccination and gene-based therapy outcomes. The noninvasive nature of oral delivery lends to ease of dosing, which can facilitate convenience and patient compliance. Moreover, oral administration allows for both local and systemic production of therapeutic genes or, in the case of DNA vaccination, mucosal and systemic immunity. Here, we describe the methods to produce a dual biomaterial, oral DNA delivery system composed of chitosan (CS) and zein (ZN). In this system, CS serves to encapsulate and deliver DNA cargo to intestinal cells in the form of CS-DNA nanoparticles (CS-DNA NPs), while ZN is used to form a protective matrix around the CS-DNA NPs that prevent degradation during gastric transit but then degrades to release the CS-DNA NPs for transfection upon entry into the intestines. These particles have demonstrated the ability to effectively protect cargo DNA from simulated gastric degradation in vitro and mediate transgene production in vivo, making them an effective oral gene delivery system.

Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose,improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of −20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0–24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.

Controlled release of silica-coated insulin-loaded chitosan nanoparticles as a promising oral administration system

BackgroundOral insulin administration has recently become one of the most exciting research subjects. Different approaches have been carried out to get an effective oral insulin delivery system using nanotechnology. The development of a delivery system that overcomes the difficulties of oral insulin administration, achieving high stability and minimal side effects, is still an urgent need. Therefore, this study is considered one of the efforts to design a new prospective drug delivery nano-composite (silica-coated chitosan-dextran sulfate nanoparticles).MethodsChitosan-dextran sulfate nanoparticles (CS-DS NPs) were prepared via a complex coacervation method and then coated with silica. Uncoated and silica-coated CS-DS NPs were physically characterized via different techniques. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis, and atomic force microscopy (AFM) have been used to investigate the chemical elements, size, morphology, and surface properties of the prepared formulations. Differential scanning calorimetry (DSC) to assess the thermal properties of formed nano-formulations. Fourier transform infrared (FT-IR) spectroscopy investigated the silica coat and chitosan interaction. The encapsulation efficiency was evaluated using high-performance liquid chromatography (HPLC) analysis. The insulin release profile of nano-formulations was performed with and without silica coat at two different pHs (5.5,7), nearly simulating the environment of the gastrointestinal tract (GIT).ResultsThe silica-coated CS-DS NPs revealed interesting physicochemical properties exemplified by suitable core particle size obtained by TEM images (145.31 ± 33.15 nm), hydrodynamic diameter (210 ± 21 nm), high stability indicated by their zeta potential value (-32 ± 3.2 mV), and adequate surface roughness assessed by AFM. The encapsulation efficiency of insulin-loaded chitosan nanoparticles (ICN) was (66.5%) higher than that of insulin-chitosan complex nanoparticles (ICCN). The silica-coated ICN demonstrated a controlled insulin release profile at pHs (5.5 and 7) compared with uncoated ICN.ConclusionThe silica-coated ICN can be an efficient candidate as a desired oral delivery system, overcoming the common obstacles of peptides and proteins delivery and achieving high stability and controlled release for further applications.