Oral Drug Delivery System Research Articles

Cellulose nanocrystals as an innovative superdisintegrant for oral dispersible tablets

Oral Dispersible Tablets (ODTs), designed for rapid disintegration in the oral cavity, offer advantages such as easy administration for diverse populations and faster drug absorption. Microcrystalline cellulose (MCC) has been a traditional choice as a disintegrant, but its limitations have led to increased interest in cellulose nanocrystals (CNCs). This study focuses on obtaining and characterizing CNCs derived from MCC by sulfuric acid hydrolysis, exploring different times and drying methods (lyophilization or spray drying). At a 50 % v/v acid concentration for 60 min at 45 °C it was possible to extract CNC with a 76 % yield. When lyophilized, CNC micrographs showed large aggregates with few isolated particles, while the spray-dried samples were seen as free, elongated particles. The resulting CNCs, with enhanced properties like high hydrophilicity and surface area, are investigated for their impact on ODT formulations. All of them disintegrated faster than 10 s. A comprehensive analysis of ODTs' disintegration mechanism was also undertaken. The drying method dictates the predominant disintegration mechanism, even though this is also influenced by the nanoparticle size. Therefore, the study contributes insights into the potential of CNCs as innovative superdisintegrants, offering a promising path for improving oral drug delivery systems.

Cloisite® 20A and polymer hydrogel as nano-vehicle for targeted and sustained release of amitriptyline

A class of nanomaterials known as anionic and cationic clays has drawn a lot of interest as a potential medication delivery vehicle. Therefore, cloisite® 20A (C-20A), chitosan hydrogel (CH) and sodium alginate hydrogel (Alg) were used as a carrier for sustained release of amitriptyline drug (AMT) as oral osmotic drug delivery system. AMT was intercalated inside the interlayer space of C-20A as well as wrapped inside CH and Alg hydrogels and prepared AMT/C-20A, AMT/CH and AMT/Alg hybrids. The intercalation of AMT inside the layer of C-20A and hydrogels were confirmed by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The contents of intercalated AMT in the AMT/C-20A, AMT/CH and AMT/Alg was determined to be 10–12 %. The release of AMT from AMT/C-20A, AMT/CH and AMT/Alg were studied at a variable value of pH (1.2–7.4). The dissolution of AMT from the AMT/C-20A, AMT/CH and AMT/Alg into the release medium was found to be a maximum (97 %, 60 % and 80 %) at pH 6.8 as the optimum pH for AMT release, and further kinetics of the drug release from the hybrids were explored. The results were fitted well to Freundlich diffusion relationship. The high release of the AMT from C-20A and CH hydrogel indicates that C-20A and CH hydrogel enables the intercalation of the AMT and allows them to be released into the target site. By comparing the release of AMT from C-20A and CH hydrogel, AMT release from C-20A was quite efficient and fast. Thus, to make the release of the intercalated AMT in more sustained manner, and consequently reduce frequency of AMT administration, AMT/C-20A was further wrapped inside CH (AMT/C-20A/CH) and Alg hydrogels (AMT/C-20A/Alg) and found the release of AMT drug in more sustainable manner and reduced the frequency of AMT administration.

An oral bioactive chitosan-decorated doxorubicin nanoparticles/bacteria bioconjugates enhance chemotherapy efficacy in an in-situ breast cancer model

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.

Oral Delivery of Photopolymerizable Nanogels Loaded with Gemcitabine for Pancreatic Cancer Therapy: Formulation Design, and in vitro and in vivo Evaluations.

Gemcitabine (GEM) faces challenges of poor oral bioavailability and extensive first-pass metabolism. Currently, only injectable formulations are available for clinical use. Hence, there is an urgent demand for the development of advanced, efficacious, and user-friendly dosage forms to maintain its status as the primary treatment for pancreatic ductal adenocarcinoma (PDAC). Nanogels (NGs) offer a novel oral drug delivery system, ideal for hydrophilic compounds like GEM. This study aims to develop NGs tailored for GEM delivery, with the goal of enhancing cellular uptake and gastrointestinal permeability for improved administration in PDAC patients. We developed cross-linked NGs via photopolymerization of methacryloyl for drug delivery of GEM. We reveal characterization, cytotoxicity, and cellular uptake studies in Caco-2 and MIA PaCa-2 cells. In addition, studies of in vitro permeability and pharmacokinetics were carried out to evaluate the bioavailability of the drug. Our results show NGs, formed via photopolymerization of methacryloyl, had a spherical shape with a size of 233.91±7.75 nm. Gemcitabine-loaded NGs (NGs-GEM) with 5% GelMA exhibited efficient drug loading (particle size: 244.07±19.52 nm). In vitro drug release from NGs-GEM was slower at pH 1.2 than pH 6.8. Cellular uptake studies indicated significantly enhanced uptake in both MIA PaCa-2 and Caco-2 cells. While there was no significant difference in GEM's AUC and Cmax between NGs-GEM and free-GEM groups, NGs-GEM showed markedly lower dFdU content (10.07 hr∙μg/mL) compared to oral free-GEM (19.04 hr∙μg/mL) after oral administration (p<0.01), highlighting NGs' efficacy in impeding rapid drug metabolism and enhancing retention. In summary, NGs enhance cellular uptake, inhibit rapid metabolic degradation of GEM, and prolong retention after oral administration. These findings suggest NGs-GEM as a promising candidate for clinical use in oral pancreatic cancer therapy.

Construction and in vitro/in vivo evaluation of menantine hydrochloride oral liquid sustained-release drug delivery system

Objective The purpose of the present study was to formulate a menantine hydrochloride (MH) sustained-release suspension. Methods Menantine hydrochloride drug resin complex (MH-DRC) was prepared with strong acid cation exchange resin as carrier using water bath method. The MH-DRC was characterized using scanning electron microscopy, X-ray diffraction and infrared spectroscopy. The MH-coated microcapsule (MH-CM) with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. The rats were given both the MH sustained-release suspension and the commercial MH sustained-release capsule by intragastric administration. The plasma concentration-time curves and related pharmacokinetic parameters were also investigated using a non-atrioventricular model. Results MH and ion-exchange resin were ionically bonded. AmberliteIRP®69 had a higher affinity for MH at the initial concentration of 5 mg·mL−1 and a reaction temperature of 25.0 ± 0.5 °C. In vitro drug release profile showed that both the drug resin complex and the coated microcapsules had a certain level of sustained-release effect. The t1/2 of MH sustained-release suspension was extended from 68.44 h to 72.79 h with the peak blood concentration being decreased to 3.56 μg·mL−1 and the Tmax extended to 12 h compared with the commercial MH sustained-release capsule. The concentration-time curve of the self-made MH sustained-release suspension was flattened and the average relative bioavailability (Fr ) was 116.65% compared with the commercial MH sustained-release capsules. Conclusions The findings showed that the MH sustained-release suspension was successfully formulated with acceptable pharmacokinetic indices for effective treatment of Alzheimer’s disease.

Current Advances of Nanomaterial-Based Oral Drug Delivery for Colorectal Cancer Treatment.

Colorectal cancer (CRC) is a common malignant tumor, and traditional treatments include surgical resection and radiotherapy. However, local recurrence, distal metastasis, and intestinal obstruction are significant problems. Oral nano-formulation is a promising treatment strategy for CRC. This study introduces physiological and environmental factors, the main challenges of CRC treatment, and the need for a novel oral colon-targeted drug delivery system (OCDDS). This study reviews the research progress of controlled-release, responsive, magnetic, targeted, and other oral nano-formulations in the direction of CRC treatment, in addition to the advantages of oral colon-targeted nano-formulations and concerns about the oral delivery of related therapeutic agents to inspire related research.

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.

A Research Work on Design, Development and In-Vitro Evaluation of Losartan Potassium Loaded Pectinate Microspheres

One of the special and innovative drug delivery strategies is the use of microspheres, which can increase a drug's effectiveness by preventing drug dilution in bodily fluids, allowing drug localization and targeting at a specific site, and maintaining drug concentration between MEC and MTC levels.Microspheres are characterized as roughly spherical, solid particles with sizes between 1 to 1000 μm that are intended to be covered in protective materials such as polymeric or waxy coatings. One of the more innovative methods in the field of oral controlled drug delivery systems is the use of microsphere dosage forms, which target a specific area of the body for a prolonged period of time, allowing for more effective local drug delivery as well as improved systemic drug. The % yield of all the losartan potassium loaded pectinate microsphere formulations (LM1 to LM5) was found within the range from 76.74 ± 3.79 % to 89.06 ± 2.67 %.The % entrapment efficiency and particle size of the prepared losartan potassium loaded pectinate microsphere formulations (LM1 to LM5) was found within the range from 63.68 ± 3.55 % to 84.78 ± 2.27 % and 0.78 ± 0.14 mm to 0.91 ± 0.05 mm respectively. Formulations LM1 to LM5 showed 2.12 % to 12.46 % mucoadhesion up to 6 hours in simulated gastric fluid (pH 1.2, 0.1N HCl) and 74.28 % to 96.04 % mucoadhesion up to 6 hours in simulated intestinal fluid (phosphate buffer, pH 6.8).

Oral Administration of Antimicrobial Peptide NZ2114 Through the Microalgal Bait Tetraselmis subcordiformis (Wille) Butcher for Improving the Immunity and Gut Health in Turbot (Scophthalmus maximus L.).

Antibiotics are widely used in aquaculture to treat the bacterial diseases. However, the improper use of antibiotics could lead to environmental pollution and development of resistance. As a safe and eco-friendly alternative, antimicrobial peptides (AMPs) are commonly explored as therapeutic agents. In this study, a mutant strain of Tetraselmis subcordiformis containing AMP NZ2114 was developed and used as an oral drug delivery system to reduce the use of antibiotics in turbot (Scophthalmus maximus) aquaculture. The gut, kidney, and liver immune-related genes and their effects on gut digestion and bacterial communities in turbot fed with NZ2114 were evaluated in an 11-day feeding experiment. The results showed that compared with the group fed with wild-type T. subcordiformis, the group fed with T. subcordiformis transformants containing NZ2114 was revealed with decreased levels of both pro-inflammatory factors (TNF-α and IL-1β), inhibitory effect on Staphylococcus aureus, Vibrio parahaemolyticus, and Vibrio splendidus demonstrated by the in vitro simulation experiments, and increased richness and diversity of the gut microbiota of turbot. In conclusion, our study provided a novel, beneficial, and low-cost method for controlling bacteria in turbot culture through the oral drug delivery systems.

PH-responsive interface conversion efficient oral drug delivery platform for alleviating inflammatory bowel disease.

A key challenge for the effective treatment of intestinal diseases, including inflammatory bowel disease (IBD), is to develop an oral drug delivery system that can resist gastric acid erosion and efficiently release drugs after rapid entry into the intestine. In the present work, we developed oral composite nanoparticles (MSZ@PRHS) consisting of a rough mesoporous silica (RHS) loaded with Mesalazine (MSZ) and a CAP polymer membrane for targeted relief of inflammation in colitis. At the pH values of the simulated stomach and small intestine, the release rate of MSZ from MSZ@PRHS was low, while at the pH values of the simulated colon, the release rate of MSZ was high. In dextran sulfate sodium salt (DSS)-induced acute colitis mouse model, compared with oral administration of the drug Mesalazine in the equivalent solution form, oral administration of PRHS loaded with drug-loaded nanoparticles can significantly alleviate the symptoms of inflammatory bowel disease, and improve the therapeutic effect. We propose that the intestinal microenvironment provides an interface for nanocomposites switch and a promising drug delivery platform for the management and treatment of many intestinal diseases, where controlled drug release and prolonged residence time are required.

ADVANCEMENTS IN MICRONEEDLE TECHNOLOGY: COMPREHENSIVE INSIGHTS INTO VERSATILE DRUG DELIVERY MECHANISMS

Microneedle-based transdermal medication administration is a revolutionary drug delivery technique that has advantages over parenteral and oral drug delivery systems. They are convenient, painless, safe, and effective. Due to the skin’s stratum corneum layer, the majority of drugs only have a limited impact, which constitutes a thickness of about 10 to 15 µm and acts as a barrier for molecules to reach the site of action, allowing just a few molecules to pass through. To overcome this, many researchers have concentrated on using microneedles to bypass the stratum corneum barrier. The main goal of microneedles is to get the drug into the epidermis without disrupting nerve endings. Micron-sized channels created by the skin layer being broken by microneedles transport the medication directly to the epidermis or higher dermis, avoiding the barrier layer and into the systemic circulation. As a result, the microneedle can improve transdermal drug delivery. Microneedles are fabricated in different forms, such as “Solid Microneedles,” “Coated Microneedles,” “Dissolving or Biodegradable Microneedles,” “Hollow Microneedles” and Hydrogel-forming Microneedles, through the use of components including polymers, polysaccharides, silicon, and metals. Micromolding, laser cutting, dip coating, 3D printing and its techniques are just a few of the processes used to make microneedles. Recently, microneedles have become popular for delivering drugs, genes, proteins, RNA and vaccines, demonstrating significant therapeutic effects. A variety of nano-carriers, along with different delivery methods, assist in emphasizing the use of microneedles in the meantime.

Semi-solid extrusion 3D printing of functionalized polyethylene oxide gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort (Leonurus cardiaca L.) dry extract

Anxiety disorders are the most prevalent psychiatric disorders and are associated with a high burden of illness. Combining synthetic and native-origin compounds in treating such disorders could provide true benefits in terms of therapeutic efficacy. In the present study, we combined triazolobenzodiazepine and motherwort (Leonurus cardiaca L.) dry extract for such applications.&#x0D; The aim. The aim of this study was to develop aqueous polyethylene oxide (PEO) composite gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort herb dry extract for semi-solid extrusion (SSE) 3D printing. The printability of such gels and the physicochemical properties of the final 3D-printed drug preparations were investigated.&#x0D; Materials and methods. A new drug substance, 1,2,3-triazolo-1,4-benzodiazepine (MA-253) was synthesized and used to formulate oleogels and electrospun nanofibers for 3D printing. The plant-origin dry extract was prepared from a motherwort tincture and valine. The aqueous PEO gels loaded with a synthetic drug (MA-253) containing nanofibers and a valine-modified motherwort extract were prepared and subsequently used in the SSE 3D printing experiments. The homogeneity, viscosity and 3D printability of composite PEO gels were verified. The phytochemical assay of flavonoids in the 3D-printed drug preparations was conducted with the European pharmacopoeia spectrophotometric method.&#x0D; Research results. Three experimental gel formulations loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort dry extract were developed and tested for the SSE 3D printing applications. The present three gels showed good SSE 3D printability without any significant printing flaws. The SSE 3D-printed lattices prepared from the aqueous PEO gels containing 100 mg/ml of motherwort extract showed the most promising 3D printing performance. The 3D-printed drug preparations were entirely dissolved in purified water (22±2 °C) within 20 minutes, thus suggesting their applicability in oral administration.&#x0D; Conclusions. Novel aqueous PEO gel formulations loaded with nanofibrous 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort herb extract are feasible for pharmaceutical SSE 3D printing. The present composite PEO gels enable the preparation of printed oral immediate-release drug delivery systems for new triazolobenzodiazepine derivatives and a drug therapy supportive plant extract

Formulation and evaluation of mucoadhesive microspheres of metronidazole

Objective: Develop and evaluate mucoadhesive microspheres using Chitosan, Sodium alginate, and Sodium carboxymethyl cellulose (NaCMC) for sustained oral delivery of Metronidazole, aiming to improve bioavailability. Methods: Metronidazole-loaded microspheres were prepared via ionotropic gelation method with varying polymer ratios. Particle size, entrapment efficiency, swelling index, mucoadhesion (sheep mucosae), morphology (SEM), in-vitro wash-off test, drug release profile, and stability (6 months) were evaluated. Results: Chitosan content positively correlated with microsphere size. Entrapment efficiency ranged from 51.43% to 94.15%. Chitosan-based formulations, especially MTZ-7 (Chitosan:NaCMC, 3:1), displayed the highest mucoadhesion. SEM analysis revealed rough, spherical microspheres with a continuous polymeric coat. In-vitro wash-off test demonstrated prolonged residence time for Chitosan formulations. Sustained drug release was observed throughout the study, with MTZ-7 exhibiting the most desirable release profile. Stability studies showed no significant changes in drug release for selected formulations after 6 months. Conclusions: Chitosan-based microspheres, particularly MTZ-7, demonstrated superior mucoadhesive properties, sustained and controlled drug release, and desirable stability. These findings suggest the potential of Chitosan-based microspheres as a promising oral drug delivery system for Metronidazole, potentially addressing bioavailability concerns and improving therapeutic efficacy.

The Design and Optimization of Fast-dissolving Oral Drug Delivery System (ODDS) of Valproic Acid (VLA) an Anti-epileptic Category Drug

Objective: Develop and optimize a fast-dissolving oral drug delivery system (ODDS) for Valproic acid (VLA), an anti-epileptic drug, using Design of Experiments (DoE). Methodology: DoE, a powerful tool for optimizing formulations, was employed to investigate the impact of various factors on the dissolution rate of VLA ODDS. Key factors studied included superdisintegrants (sodium starch glycolate, crospovidone), diluents (lactose, microcrystalline cellulose), and lubricants (magnesium stearate). A Box-Behnken design was used to create experimental runs, and the dissolution rate at 30 minutes was chosen as the response variable. Results: The DoE analysis revealed significant interactions between factors affecting the dissolution rate. The formulation containing sodium starch glycolate, lactose, and low magnesium stearate concentration exhibited the fastest dissolution rate (Q30 &gt; 85% in 10 minutes). Conclusion: This study successfully designed and optimized a fast-dissolving ODDS for VLA using DoE. The optimized formulation offered rapid drug release, potentially improving patient compliance and therapeutic efficacy. This approach demonstrates the effectiveness of DoE in optimizing pharmaceutical formulations for enhanced performance. The findings indicated that the RSM was effectively utilized in developing valproic acid fast dispersible tablets, thus representing a significant progress in the treatment of epileptic seizures.

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.

The investigation on sialic acid-modified pectin nanoparticles loaded with oxymatrine for orally targeting and inhibiting the of ulcerative colitis

The aim of the study was to develop an oral targeting drug delivery system (OTDDS) of oxymatrine (OMT) to effectively treat ulcerative colitis (UC). The OTDDS of OMT (OMT/SA-NPs) was constructed with OMT, pectin, Ca2+, chitosan (CS) and sialic acid (SA). The obtained particles were characterized in terms of particle size, zeta potential, morphology, drug loading, encapsulation efficiency, drug release and stability. The average size of OMT/SA-NPs was 255.0 nm with a zeta potential of −12.4 mV. The loading content and encapsulation efficiency of OMT/SA-NPs were 14.65% and 84.83%, respectively. The particle size of OMT/SA-NPs changed slightly in the gastrointestinal tract. The nanoparticles can delivery most of the drug to the colon region. In vitro cell experiments showed that the SA-NPs had excellent biocompatibility and anti-inflammation, and the uptake of SA-NPs by RAW 264.7 cells was time and concentration-dependent. The conjugated SA can help the internalization of NPs into target cells. In vivo experiments showed that OMT/SA-NPs had a superior anti-inflammation effect and the effect of reducing UC, which was attributed to the delivery most of OMT to the colonic lumen, the specific targeting and retention in colitis site and the combined anti-inflammation of OMT and NPs.

A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery

Abstract Pharmaceutical scientists have long struggled to develop reliable and efficient systems of administering insulin orally due to multiple barriers, including stomach acidity, enzymatic degradation, and mucus barriers. However, various strategies were developed to avoid insulin degradation in the gastrointestinal tract (GIT) and promote membrane permeability and biological activity. Among these strategies, chitosan polymer-based carriers are widely researched due to their ability to protect insulin in the alimentary canal and deliver it effectively through the intestinal mucosa, improving its bioavailability. To improve chitosan properties, chemical and physical modifications have been developed, and recently, nanoparticles, microparticles, and beads of chitosan exhibited potential systems for oral insulin delivery (OID). This review facilitates an outline of the types of diabetes mellitus, insulin biosynthesis, and gastrointestinal barriers against oral insulin. Moreover, the limitations of subcutaneous insulin delivery and alternative routes of administration are also discussed. As an ideal and most convenient oral administration route, the challenges of safe insulin delivery through the GIT and strategies to elevate its bioavailability are highlighted. In addition, this review focuses on recent advancements in chitosan based carriers for OID and their potential future applications.

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.

Potential of Milk-Derived Extracellular Vesicles as Carriers for Oral Delivery of Active Phytoconstituents.

Extracellular vesicles (EVs) play a crucial role in intercellular communication and have the potential to serve as in vivo carriers for delivering active molecules. The biocompatibility advantages of EVs over artificial nanocarriers create new frontiers for delivering modern active molecules. Milk is a favorable source of EVs because of its high bioavailability, low immunogenicity, and commercial producibility. In this review, we analyzed the advantages of milk-derived EVs in the oral delivery of active molecules, discussed their research progress in delivering active phytoconstituents, and summarized the necessary technologies and critical unit operations required for the development of an oral delivery system based on EVs. The review aims to provide innovative ideas and fundamental quality control guidelines for developing the next-generation oral drug delivery system based on milk-derived EVs.

PULSATILE DRUG DELIVERY SYSTEMS THE NOVEL APPROACH

Oral pulsatile drug delivery systems (PDDS) are intended to induce programmable lag phases before a quick and quantifiable, repeated, or prolonged medication release. As a result, they are gaining popularity due to their inherent suitability for achieving chronotherapeutic goals, which have just been highlighted concerning several prevalent chronic illnesses characterized by typical night or early-morning recurring symptoms (e. g. bronchial asthma, heart attack, rheumatoid arthritis, early-morningawakening). Furthermore, time-based colonic release is possible when pulsatile delivery devices are correctly modified to overcome unexpected gastric emptying and give delay periods that roughly match the small intestine transit time. Oral pulsatile administration is accomplished using several release platforms, including reservoir, capsular, and osmotic devices. The current review article addressed the topics that followed: the reason pulsatile drug delivery systems have been invented; diseases for which pulsatile release is necessary; classification, advantages and disadvantages; methods used in the current systems; the situation nowadays and its potential for the future; recent advancements, and especially, the previous five to ten years of research on pulsatile drug delivery conducted by researchers using a variety of drugs for a variety of diseases.