Oral Drug Delivery Vehicles Research Articles

Oral drug delivery vehicle for insulin and curcumin based on egg albumin-dextran conjugate: In vitro and in vivo studies

The increasing desire for oral delivery vehicle systems encouraged the development of micro and nano encapsulation technologies to protect drugs against gastric and enzymatic degradation. This study aimed to develop egg albumin-dextran conjugate as a delivery vehicle for oral administration. For this purpose, insulin was selected as a macromolecule drug and curcumin as a natural lipophilic polyphenol, both show negative absorption kinetics in gastrointestinal tract. Egg albumin-dextran conjugate was prepared by Maillard reaction under mild conditions and subsequently be used to encapsulate insulin and curcumin, respectively. The encapsulation efficiency reached to 97 % and 95.5 % at 300 mg/ml of insulin and curcumin, respectively. The profile of in vitro drug release for the insulin and curcumin indicates that approximately 60 % of the drugs were partially retained by the conjugate in gastric pH environment while a more extensive release was observed under intestinal pH conditions. Application of oral administration of insulin conjugate (IC) and/or curcumin conjugate (CC) to streptozotocin (STZ) induced diabetic rats was investigated for 6 weeks and compared with trade insulin drug. Fifty-four albino rats were separated into nine equivalent groups. Control, insulin conjugate (IC), curcumin conjugate (CC), and IC + CC. The remaining groups injected with STZ and subsequently received vehicle, IC, CC, IC + CC, and trade insulin drug; respectively.Interestingly, insulin conjugate and/or curcumin conjugate significantly reduced hyperglycemia, hyperlipidemia, decreased fructosamine level, decreased HOMA-IR, increased insulin level, increased HOMA-β, increased antioxidant defense molecules, along with modulating morphological pancreatic degeneration caused by STZ. In conclusion, oral insulin-conjugate is more effective than the trade insulin drug. Also, curcumin-conjugate has a promising role as antidiabetic agent as it may contribute in β-cells regeneration. Further, the combination between them may have synergetic antidiabetic effect. But, more detailed studies should be done to investigate the possible mechanisms of their antidiabetic effect.

An exosomal approach for oral delivery of resveratrol: Implications for inflammatory bowel disease treatment in rat model

AimsResveratrol (RSV) is a polyphenolic substance found in numerous natural products. Despite the wide range of therapeutic activities, including antioxidant and anti-inflammatory effects, the poor pharmacokinetic characteristics decrease the RSV bioavailability following oral administration. Milk-derived exosomes (MEXOs), as a class of natural nanocarriers, are promising candidates for oral drug delivery approaches. Main methodsThe current study developed RSV-loaded MEXOs to enhance the RSV oral bioavailability, introducing a suitable exosomal formulation for suppressing colon inflammation in acetic acid-induced rat models. Key findingsThe results showed a remarkable encapsulation efficiency of 83.33 %. The in vitro release profile demonstrated a good retaining capability in acidic conditions (pH 1.2) and a considerable release in a simulated duodenal environment (pH 6.8). According to the permeability study, encapsulation of RSV improved its transportation across the Caco-2 monolayer. Moreover, the in vivo and histological analysis results proved that the RSV-MEXOs formulation successfully alleviates the inflammation in colitis rat models and effectively relieves the colitis. SignificanceOur findings suggest that MEXOs should be of great attention as promising oral drug delivery vehicles for further clinical evaluations.

Algae-Based Nanoparticles for Oral Drug Delivery Systems.

Drug administration by oral delivery is the preferred route, regardless of some remaining challenges, such as short resident time and toxicity issues. One strategy to overcome these barriers is utilizing mucoadhesive vectors that can increase intestinal resident time and systemic uptake. In this study, biomimetic nanoparticles (NPs) were produced from 14 types of edible algae and evaluated for usage as oral DDSs by measuring their size, surface charge, morphology, encapsulation efficiency, mucoadhesion force, and cellular uptake into Caco-2 cells. The NPs composed of algal materials (aNPs) exhibited a spherical morphology with a size range of 126-606 nm and a surface charge of -9 to -38 mV. The mucoadhesive forces tested ex vivo against mice, pigs, and sheep intestines revealed significant variation between algae and animal models. Notably, Arthospira platensis (i.e., Spirulina) NPs (126 ± 2 nm, -38 ± 3 mV) consistently exhibited the highest mucoadhesive forces (up to 3127 ± 272 µN/mm²). Moreover, a correlation was found between high mucoadhesive force and high cellular uptake into Caco-2 cells, further supporting the potential of aNPs by indicating their ability to facilitate drug absorption into the human intestinal epithelium. The results presented herein serve as a proof of concept for the possibility of aNPs as oral drug delivery vehicles.

Rational design of oral drugs targeting mucosa delivery with gut organoid platforms.

Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads (i.e., immunogens) against gastric damage. In this study, hollowed nanocarriers (NCs: silica nanospheres and gold nanocages) with poly-l-lysine (PLL) coating and mammalian orthoreovirus cell attachment protein σ1 functionalization (NC-PLL-σ1) were explored as functional oral drug delivery vehicles (ODDVs). The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells (M-cells) mediated transcytosis (via σ1-α2-3-linked sialic acids adherence) across gastrointestinal epithelia. PLL coating provided protection and slow-release of rhodamine 6G(R6G), a model payload. The transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in vitro. When compared with other experimental groups, the fully functionalized ODDV system (with PLL-σ1) demonstrated two significant advantages: a significantly higher transport efficiency (198% over blank control at 48h); and protection of payloads which led to both better transport efficiency and extended-release of payloads (61% over uncoated carriers at 48h). In addition, it was shown that the M cell presence in intestinal organoid monolayers (modulated by Rank L stimulation) was a determining factor on the transport efficiency of the ODDVs: more M-cells (induced by higher Rank L) in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload (R6G). The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines.

Incorporation of Loratadine-Cyclodextrin Complexes in Oral Thin Films for Rapid Drug Delivery

Rapidly dissolving polymer thin films, or oral thin films (OTFs), have recently emerged as an improved oral drug delivery vehicle with its ability to bypass liver first pass metabolism, longer shelf-life, and simpler transport and distribution requirements, compared to traditional tablets and liquid formulations. Loratadine (LOR), an antihistamine commonly used to treat allergic rhinitis, undergoes liver first pass metabolism and is a prime candidate for incorporation within an OTF. However, loratadine is a BCS II drug with low aqueous solubility. Herein, the solubility of loratadine was improved by complexation with methyl β-cyclodextrin (MBCD) by co-evaporation of 2:1, 1:1, and 1:2 LOR:MBCD ratios and incorporation into a pullulan-based OTF at 4 wt% by solvent casting at 50 °C for 30 – 35 min. A therapeutically relevant 10 mg LOR dose could be prepared in a 3 cm by 3 cm OTF. The feasibility of complexation was observed with a Bs-type phase solubility diagram, and complexation itself was confirmed via differential scanning calorimetry (DSC) by disappearance of the LOR melting peak, Fourier-transform infrared spectroscopy (FTIR) by shifting of the C=O peak, via 1H NMR spectroscopy by downfield shifting and change in peak multiplicity of the LOR aromatic protons, and via diffusion-ordered spectroscopy by a decrease in the diffusion coefficient of LOR:MBCD complex. LOR:MBCD could be incorporated homogeneously throughout an OTF, and LOR:MBCD OTFs exhibited reasonable mechanical strength and endured 12 ± 3 folds before breaking. LOR:MBCD OTFs disintegrated within 38 ± 10 s. The cumulative in vitro release of LOR:MBCD OTFs peaked at 80 % within 3–4 min of dissolution, and LOR in LOR:MBCD OTFs exhibited permeability across a 0.22 μm nitrocellulose membrane, demonstrating its applicability as a rapid drug delivery vehicle.

Preparation and evaluation of chitosan-alginate/carrageenan hydrogel for oral drug delivery in the treatment of diabetes

Marine beds are an untapped resource of bioactive materials which can be explored for drug delivery applications. In the present study, a hydrogel was developed with an optimal concentration of sodium alginate-chitosan core polyelectrolytic complex loaded with anti-diabetic drug metformin and coated with ĸ-Carrageenan as an efficient oral drug delivery vehicle. The formulation was optimized by changing parameters such as concentration of polymers, amount of cross-linker and the type and amount of coating material. The prepared hydrogels were characterized for their structural integrity using instrumental techniques such as FTIR, XRD, DSC, and SEM while the physical properties were assessed by evaluating its thickness, UV barrier ability and swelling degree. In vitro study demonstrated the influence of presence and type of coating material affecting drug delivery process. The study suggested that coating with 3% ĸ-Carrageenan (A19) was found most suitable for oral drug delivery since it could resist diffusion of drug in the stomach (pH 1.2) so that maximum drug could reach the intestine (pH 7.4) for absorption. Metformin loaded hydrogel (A20) released ~49% drug in the simulated gastric fluid (pH 1.2). In the simulated intestinal fluid (pH 7.4) both the hydrogel exhibited a sustained release pattern lasting for more than 4 h. Investigation of drug release kinetics using different mathematical models showed that Higuchi model was the best fit release model with R2 ⩾ 0.973. The results indicated that the prepared hydrogels could be potential drug delivery vehicle toward intestine as well as for extended release to colon targeted drug delivery.

Multifunctional Milk-Derived Small Extracellular Vesicles and Their Biomedical Applications.

In recent years, small extracellular vesicles (sEVs) have been regarded as the next generation of novel delivery systems after lipid nanoparticles because of their advantages and huge prospects in drug delivery. Studies have shown that sEVs are abundant in milk and therefore can be a large and economical source of sEVs. Natural milk-derived small extracellular vesicles (msEVs) have important functions such as immune regulation, anti-bacterial infection, anti-oxidative, etc., and play a beneficial role in human health at multiple levels, including intestinal health, bone/muscle metabolism, and microbiota regulation. In addition, because they can pass the gastrointestinal barrier and have low immunogenicity, good biocompatibility, and stability, msEVs are considered a crucial oral drug delivery vehicle. Moreover, msEVs can be further engineered for targeted delivery to prolong the circulation time or enhance local drug concentrations. However, msEVs separation and purification, complex contents, and quality control hinder their application in drug delivery. This paper provides a comprehensive review of the biogenesis and characteristics, isolation and purification, composition, loading methods, and function of msEVs, based on which their applications in biomedical fields are further explored.

Reinvention of starch for oral drug delivery system design

Starch is a polysaccharide with varying amylose-to-amylopectin ratios as a function of its biological sources. It is characterized by low shear stress resistance, poor aqueous/organic solubility and gastrointestinal digestibility which limit its ease of processing and functionality display as an oral drug delivery vehicle. Modulation of starch composition through genetic engineering primarily alters amylose-to-amylopectin ratio. Greater molecular properties changes require chemical and enzymatic modifications of starch. Acetylation reduces water solubility and enzymatic digestibility of starch. Carboxymethylation turns starch acid-insoluble and aggregative at low pHs. The summative effects are sustaining drug release in the upper gut. Acid-insoluble carboxymethylated starch can be aminated to provide an ionic character essential for hydrogel formation which further reduces its drug release. Ionic starch can coacervate with oppositely charged starch, non-starch polyelectrolyte or drug into insoluble, controlled-release complexes. Enzymatically debranched and resistant starch has a small molecular size which confers chain aggregation into a helical hydrogel network that traps the drug molecules, protecting them from biodegradation. The modified starch has been used to modulate the intestinal/colon-specific or controlled systemic delivery of oral small molecule drugs and macromolecular therapeutics. This review highlights synthesis aspects of starch and starch derivatives, and their outcomes and challenges of applications in oral drug delivery.

Newly Synthesized Lignin Microparticles as Bioinspired Oral Drug-Delivery Vehicles: Flavonoid-Carrier Potential and In Vitro Radical-Scavenging Activity.

The aim of the present study was to synthesize lignin microparticles, to evaluate their physicochemical, spectral, morphological and structural characteristics, to examine their encapsulation and in vitro release potential and behaviour towards the flavonoid morin in simulated physiological medium and to assess the in vitro radical-scavenging potential of the morin-loaded lignin microcarrier systems. The physicochemical, structural and morphological characteristics of alkali lignin, lignin particles (LP) and morin-encapsulated lignin microparticles (LMP) were determined based on particle size distribution, SEM, UV/Vis spectrophotometric, FTIR and potentiometric titration analyses. The encapsulation efficiency of LMP was 98.1%. The FTIR analyses proved that morin was successfully encapsulated in the LP without unexpected chemical reactions between the flavonoid and the heteropolymer. The in vitro release performance of the microcarrier system was successfully mathematically described by Korsmeyer-Peppas and the sigmoidal models outlining the general role of diffusion during the initial stages of the in vitro release process in simulated gastric fluid (SGF), and the predominant contribution of biopolymer relaxation and erosion was determined in simulated intestinal medium (SIF). The higher radical-scavenging potential of LMP, as compared to that of LP, was proven via DPPH and ABTS assays. The synthesis of lignin microcarriers not only provides a facile approach for the utilization of the heteropolymer but also determines its potential for the design of drug-delivery matrices.

Milk-derived exosomes as a promising vehicle for oral delivery of hydrophilic biomacromolecule drugs

Exosomes, as promising vehicles, have been widely used in the research of oral drug delivery, but the generally low drug loading efficiency of exosomes seriously limits its application and transformation. In this study, we systematically investigated the effects of drug loading methods and physicochemical properties (lipophilicity and molecular weight) on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions. Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method, drug lipophilicity, drug molecular weight and exosome/drug proportions. Of note, we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes, which was attributed to the efficient loading capacity and sustained release behavior. Furthermore, milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs (octreotide, exendin-4 and salmon calcitonin). Collectively, our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.

Advanced research on extracellular vesicles based oral drug delivery systems.

The oral route is the most convenient and simplest mode of administration. Nevertheless, orally administration of some commonly used therapeutic drugs, such as polypeptides, therapeutic proteins, small-molecule drugs, and nucleic acids, remains a major challenge due to the harsh gastrointestinal environment and the limited oral bioavailability. Extracellular vesicles (EVs) are diverse, nanoscale phospholipid vesicles that are actively released by cells and play crucial roles in intercellular communications. Some EVs have been shown to survive with the gastrointestinal tract (GIT) and can cross biological barriers. The potential of EVs to cross the GIT barrier makes them promising natural delivery carriers for orally administered drugs. Here, we introduce the uniqueness of EVs and their feasibility as oral drug delivery vehicles (ODDVs). Then we provide a general description of the different cellular EVs based oral drug delivery systems (ODDSs) currently under study and emphasize the contribution of endogenous features and multifunctional properties of EVs to the delivery performance. The current obstacles of moving EVs based ODDSs from bench to bedside are also discussed.

Oral colon-targeting core\u2013shell microparticles loading curcumin for enhanced ulcerative colitis alleviating efficacy

BackgroundThe oral colon-targeting drug delivery vehicle is vital for the efficient application of curcumin (Cur) in ulcerative colitis (UC) treatment because of its lipophilicity and instability in the gastrointestinal tract.MethodsThe core–shell microparticle (MP) system composed of eco-friendly materials, zein and shellac, was fabricated using a coaxial electrospray technique. In this manner, Cur was loaded in the zein core, with shellac shell coating on it. The colon-targeting efficiency and accumulation capacity of shellac@Cur/zein MPs were evaluated using a fluorescence imaging test. The treatment effects of free Cur, Cur/zein MPs, and shellac@Cur/zein MPs in acute experimental colitis were compared.ResultsWith the process parameters optimized, shellac@Cur/zein MPs were facilely fabricated with a stable cone-jet mode, exhibiting standard spherical shape, uniform size distribution (2.84 ± 0.15 µm), and high encapsulation efficiency (95.97% ± 3.51%). Particularly, with the protection of shellac@zein MPs, Cur exhibited sustained drug release in the simulated gastrointestinal tract. Additionally, the in vivo fluorescence imaging test indicated that the cargo loaded in shellac@zein MPs improves the colon-targeting efficiency and accumulation capacity at the colonitis site. More importantly, compared with either free Cur or Cur/zein MPs, the continuous oral administration of shellac@Cur/zein MPs for a week could efficiently inhibit inflammation in acute experimental colitis.ConclusionThe shellac@Cur/zein MPs would act as an effective oral drug delivery system for UC management.

Central Composite Design for Formulation and Optimization of Solid Lipid Nanoparticles to Enhance Oral Bioavailability of Acyclovir.

Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties.

A concise review on preparation methods used for the development of solid lipid nanoparticles

Solid lipid nanoparticles (SLNs) are in submicron size range nanoparticles and are made of biocompatible and biodegradable materials (mainly composed of lipids and surfactants) capable of incorporating both lipophilic and hydrophilic drugs. SLNs are also considered as substitute to other colloidal drug systems, also used as controlled systems and targeted delivery. SLNs can be considered as an alternative for oral drug delivery vehicle to improve the oral bioavailability of drugs, associated reduction of drug toxicity and stability of drug in both GIT and plasma. There are different techniques used for the preparation of SLNs. Generally, the preparation of SLNs and any other nanoparticle system necessitates a dispersed system as precursor; otherwise particles are produced through the use of a particular instrumentation. This review provides the summary on the techniques or methods used for the development of SLNs of poorly water soluble drugs for improved drug delivery.
 Keywords: Solid lipid nanoparticles, controlled delivery, precursor, techniques.

Design of polysaccharidic nano-in-micro soft agglomerates as primary oral drug delivery vehicle for colon-specific targeting

Microencapsulation of polysaccharidic nanoparticles is met with nanoscale and biological performance changes. This study designs soft agglomerates as nanoparticle vehicle without nanoparticles undergoing physical processes that alter their geometry. The nanoparticles were made of high molecular weight chitosan/pectin with covalent 5-fluorouracil/folate. Nanoparticle aggregation vehicle was prepared from low molecular weight chitosan. The nanoparticles and aggregation vehicle were blended in specific weight ratios to produce soft agglomerates. Nanoparticles alone are unable to agglomerate. Adding aggregation vehicle (< 2 μm) promoted soft agglomeration with nanoparticles deposited onto its surfaces with minimal binary coalescence. The large and rough-surfaced aggregation vehicle promoted nanoparticles deposition and agglomeration. A rounder vehicle allowed assembly of nanoparticles-on-aggregation vehicle into agglomerates through interspersing smaller between larger populations. Soft agglomeration reduced early drug release, and was responsive to intracapsular sodium alginate coat to further sustain drug release. The soft agglomerates can serve as a primary oral colon-specific vehicle.

Cross-linked xanthan gum–starch hydrogels as promising materials for controlled drug delivery

The work was intended to develop a novel acrylic acid grafted hydrogel by chemical crosslinking of xanthan gum and starch under microwave irradiation. The swelling capacity of hydrogel was found to be dependent upon pH. The maximum swelling capacity of hydrogel was recorded as 32.21 g/g under the optimized conditions. The swelling capacity of hydrogel was quite higher than most of the hydrogels containing xanthan gum mentioned in the literature. Various characterization techniques including FTIR, SEM, TGA and XRD confirmed successful synthesis of hydrogel with porous morphology and better thermal stability. Synthesized hydrogel was employed as an oral drug delivery vehicle. Releasing behavior of the hydrogels for the drugs aspirin and paracetamol was studied under specific physiological conditions. The drug release was significantly higher at pH 7.4 in comparison to acidic and neutral media. Synthesized hydrogel was found to be suitable for colon-specific drug delivery. Both aspirin and paracetamol followed non-Fickian diffusion mechanism at higher pH and Fickian mechanism at lower pH. Release profiles of both the drugs were best fitted in the first order model. Hydrogel was found to be non-cytotoxic to human fibroblast cells and biocompatible, with a low hemolytic ratio. Consequently results supported potential of this non-toxic, biofriendly and appropriately tailored polysaccharide based hydrogel to be used as drug delivery carrier for controlled and site-specific drug release.

Bolalipid-Doped Liposomes: Can Bolalipids Increase the Integrity of Liposomes Exposed to Gastrointestinal Fluids?

The use of archaeal lipids and their artificial analogues, also known as bolalipids, represents a promising approach for the stabilization of classical lipid vesicles for oral application. In a previous study, we investigated the mixing behavior of three single-chain alkyl-branched bolalipids PC-C32(1,32Cn)-PC (n = 3, 6, 9) with either saturated or unsaturated phosphatidyl-cholines. We proved, that the bolalipids PC-C32(1,32C6)-PC and PC-C32(1,32C9)-PC show miscibility with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). In the present work, we extended our vesicle system to natural lipid mixtures using phosphatidylcholine from soy beans, and we investigated the effect of incorporated bolalipids on the integrity of these mixed liposomes (bolasomes) in different gastrointestinal fluids using a dithionite assay and a calcein release assay in combination with particle size measurements. Finally, we also studied the retention of calcein within the bolasomes during freeze-drying. As a main result, we could show that in particular PC-C32(1,32C6)-PC is able to increase the stability of bolasomes in simulated gastric fluid—a prerequisite for the further use of liposomes as oral drug delivery vehicles.

Carboxymethylcellulose/layered double hydroxides bio-nanocomposite hydrogel: A controlled amoxicillin nanocarrier for colonic bacterial infections treatment

In this work, a pH-sensitive carboxymethylcellulose based bio-nanocomposite hydrogel beads with different content of layered double hydroxides (LDHs) as a nanoparticle was prepared (CMC/LDH(Cu/Al)). EDX spectroscopy was used to confirm the successful composition of LDH(Cu/Al) with CMC and its presence in the hydrogel matrix. The prepared CMC/LDH(Cu/Al) bio-nanocomposite hydrogel bead characterized by XRD, FT-IR, and SEM analysis. The swelling results showed the pH-sensitive properties for all of the prepared CMC/LDH(Cu/Al). Amoxicillin (AMX) as a model of the antibiotic drug was selected to study the ability of the prepared systems as an oral drug delivery vehicle. The obtained results showed that the CMC/LDH(Cu/Al 7.5) bio-nanocomposite hydrogel bead has a good performance compared to the other prepared bio-nanocomposites. MTT assay approved the safety of this bio-nanocomposite hydrogel bead against HUVEC cells. Consistent with the obtained results, the prepared hydrogel beads could be potentially proposed as an efficient safe drug carrier for AMX oral delivery.

Synthesis, characterizations and kinetic study of metal organic framework nanocomposite excipient used as extended release delivery vehicle for an antibiotic drug

The present work was to investigate the zinc-based metal-organic frameworks (MOF-5) as oral drug delivery vehicle for the extended in-vitro release of antibiotic drug metronidazole (MTD). The MOF-5 was synthesized by the solvothermal process and characterized by a series of analytical techniques such as PXRD, FTIR, FESEM, HRTEM, TGA and BET. The TEM analysis of the drug loaded nanocomposite (MTD@MOF5) shows the particles size less than in the range of 40–90 nm in dimension. Adsorption of metronidazole on MOF-5 was then estimated as a function of pH in the aqueous drug solution, contact time and initial drug concentration. High loading of metronidazole was found to be 539.33 mg/g of MOF-5 at pH 2. The kinetic results follow the pseudo-second-order model and the isotherm was best described by Freundlich adsorption and Temkin isotherm model respectively. The comparison of in-vitro release behavior of metronidazole drug and the present nanocomposite were explored in the simulated gastric (PBS, pH 1.2) and simulated intestinal fluids (PBS, pH 7.4). The drug shows the excellent releasing power from the MTD@MOF5 nanocomposite as compare to the pure metronidazole drug in terms of availability for the extended time periods.

Bottom-Up Fabrication of Multilayer Enteric Devices for the Oral Delivery of Peptides.

To develop a planar, asymmetric, micro-scale oral drug delivery vehicle by i) fabricating microdevice bodies with enteric materials, ii) efficiently and stably loading sensitive drug molecules, and iii) capping microdevices for controlled drug release. Picoliter-volume inkjet printing was used to fabricate microdevices through additive manufacturing via drop-by-drop deposition of enteric polymer materials. Microdevice bodies with reservoirs are fabricated through deposition of an enteric polymer, Eudragit FS 30 D. A model API, insulin, was loaded into each microdevice and retained its stability during printing and release. Eudragit L 100 and/or S 100 were used to cap microdevices and control the kinetics of insulin release in simulated intestinal conditions. Microdevice morphologies and size can be tuned on the fly based on printing parameters to span from the microscale to the mesoscale. Insulin retained its stability throughout device fabrication and during in vitro release in simulated intestinal conditions. Insulin release kinetics, from burst release to no release, can be tailored by controlling the blend of the Eudragit capping material. This approach represents a uniquely scalable and flexible strategy for microdevice fabrication that overcomes limitations in loading sensitive biologics and in the tuneability of device geometries that are inherent to traditional microfabrication strategies.