Oral Drug Delivery System Research Articles

3D printed microneedles: revamping transdermal drug delivery systems.

One of the advancements of the transdermal drug delivery system (TDDS) is the development of microneedles (MNs). These micron-sized needles are used for delivering various types of drugs to address the disadvantage of other transdermal techniques as well as oral drug delivery systems. MNs have high patient acceptance due to self-administration with minimally invasive and pain compared to the parenteral drug delivery. Over the years, various methods have been adopted to evolve the MNs and make them more cost-effective, accurate, and suitable for multiple applications. One such method is the 3D printing of MNs. The development of MN platforms using 3D printing has been made possible by improved features like precision, printing resolution, and the feasibility of using low-cost raw materials. In this review, we have tried to explain various types of MNs, fabrication methods, materials used in the formulation of MNs, and the recent applications that utilize 3D-printed MNs.

PH-responsive IPN beads of carboxymethyl konjac glucomannan and sodium carboxymethyl cellulose as a controlled release carrier for ibuprofen

The convergence of polymer and pharmaceutical sciences has advanced drug delivery systems significantly. Carbohydrate polymers, especially carboxymethylated ones, offer versatile benefits for pharmaceuticals. Interpenetrating polymer networks (IPNs) combine synthetic and natural polymers to enhance drug delivery. The study aims to develop IPN beads using sodium carboxymethyl cellulose (SCMC) and carboxymethyl konjac glucomannan (CMKGM) for controlled release of ibuprofen (IB) after oral administration. Objectives include formulation optimization, characterization of physicochemical properties, evaluation of pH-dependent swelling and drug release behaviors to advance biocompatible and efficient oral drug delivery systems. The beads were analyzed using SEM, FTIR, DSC, and XRD techniques. Different ratio of polymers (CMKGM:SCMS) and crosslinker concentrations (2&4 %w/v) were used, significantly impacting bead size, swelling, drug encapsulation, and release characteristics. DSC results indicated higher thermal stability in IPN beads compared to native polymers. XRD revealed IB dispersion within the polymer matrix. IPN beads size ranged from 580 ± 0.56 to 324 ± 0.27 μm, with a nearly spherical shape. IPN beads exhibited continuous release in alkaline conditions (pH 7.4) and minimal release in acidic media (pH 1.2). These findings suggest that the formulated IPN beads can modulate drug release in both acidic and alkaline environments, potentially mitigating the gastric adverse effects often associated with oral administration of IB.

Teneligliptin hydrobromide hydrate mouth dissolving strip: Formulation and evaluation

Oral route is considered as one of the most convenient route for administration of various pharmaceutical dosage form like tablet, capsule, syrup, suspension and emulsion. Fast Dissolving Drug Delivery systems have developed various fast disintegrating preparations like Oral disintegrating film, ODF. Oral disintegrating film is the solid oral drug delivery system, in which water soluble polymer involve to disintegrate film into mouth fastly. Oral disintegrating film is superior as compare to orally disintegrating tablet as the cost of production is low. The present research was undertaken to develop oral disintegrating film of tteneligliptin hydrobromide hydrate to have rapid onset of action. of tteneligliptin hydrobromide hydrate which is an anti-diabetic. The mechanism action of Teneligliptin is to increase incretin levels (GLP-1 and GIP), which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.The concept of formulating fast disintegrating film Teneligliptin containing offers a suitable and practical approach in serving desired objective of faster disintegration and dissolution characteristics with increased bioavailability. ODF of Teneligliptin were prepared by solvent casting method and evaluated physicochemical parameters like thickness, weight variation, moisture content, folding endurance, drug content, etc. All the formulations of Teneligliptin ODF displayed optimum folding endurance, which indicates the formulation prepared can withstand handling and transportation. From the results obtained, it was concluded that the formulation of oral disintegrating film has better physical chemical properties with good disintegration property.

Characterization and in vitro evaluation of melanin nanoparticles as an oral drug delivery system: Studies using Caco-2 cell model and molecular dynamics simulations

Interest has been shown in the use of melanin nanoparticles (MNPs) for drug delivery applications. This study investigates the potential use of MNPs as an oral drug delivery system. The toxicity and cellular uptake of MNPs via intestinal barrier were evaluated using the Caco-2 cell model. Doxorubicin (DOX) was selected as a representative low bioavailability drug. The DOX-release profile of drug-loaded MNPs and molecular dynamic (MD) simulation were investigated at different pH. Our results demonstrated that MNPs synthesized from dopamine HCl are suitable as nanocarriers, presenting as monodisperse particles at mean size <300 nm. MNPs at size 89, 156, 268 nm at 3.13–50 μg/mL showed a high biocompatibiltity with Caco-2 cells, since no significant changes in %cell viability, reactive oxygen species, mitochondria membrane potential, and inflammatory cytokine were observed. The TEM results exhibited cellular internalization of MNPs into Caco-2 cells. The loading capacity (LC) and entrapment efficiency (EE) of DOX-loaded MNPs were 13.3 ± 2.7 % and 30.0 ± 3.6 %, respectively. DOX-loaded MNPs possessed a pH-dependent drug release profile. At pH 1.2, the amount of liberated DOX was 1.6- and 3.8-fold increase in comparison to pH 5 and 7.4, respectively. MD simulation clearly demonstrated that the binding affinity between polydopamines of MNPs and DOX molecules was weaker at the lower pH. These results thus support the potential use of MNPs as an oral drug delivery system particularly for drugs used in cancer treatment.

Advancements in oral insulin: A century of research and the emergence of targeted nanoparticle strategies

AbstractWith the growing prevalence of diabetes, there is an urgent demand for a user‐friendly treatment option that minimizes side effects related to the use of subcutaneous injections. Scientists have dedicated over a century to developing an oral dosage form of insulin that can be administrated orally. The oral route of administration is the most desirable route for regularly dosed drugs in terms of safety and patient compliance. However, oral delivery of insulin remains a formidable challenge due to its intrinsically limited ability to cross the intestinal epithelium membrane and susceptibility to enzymatic degradation. This article reviews oral insulin research over the past decade, with a particular focus on surface modifications of nanoparticles (NPs). Various strategies involving controlling surface charges, utilizing protective proteins, and targeting specific receptors with ligands have been explored. Notably, surface modifications of the NPs for targeting specific intestinal receptors have shown promise in enhancing insulin oral absorption and bioavailability. Advanced technologies such as oral microneedles and gene therapy have also been developed, but their safety requires further assessment. Despite encouraging preclinical results across numerous strategies, the current clinical evidence is less optimistic. In summary, the present findings highlight the substantial journey that still lies ahead before achieving successful oral delivery of insulin.Practical Applications: This review provides a summary of recent progress in oral insulin delivery, particularly highlighting surface‐modified functional nanoparticles serving as an effective drug delivery system, which offers valuable information to the researchers. Due to the limited effectiveness of oral protein drugs caused by biological barriers, innovative technologies and drug delivery systems have been developed to overcome these obstacles and achieve therapeutic goals. This review concluded that surface modifications to nanoparticles can improve insulin stability and permeability, thereby enhancing oral bioavailability. It could assist researchers in developing more effective and patient‐friendly oral drug delivery systems.

Effective in vivo reactivation of HIV-1 latency reservoir via oral administration of EK-16A-SNEDDS

The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The “shock and kill” strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to “shock” the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.

Engineered low-pathogenic Helicobacter pylori as orally tumor immunomodulators for the stimulation of systemic immune response

Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.

Prevalent Oral Drug Delivery System for Dental Care

Abstract: Oral drug delivery systems, including fluoride supplements, constitute one of the most prevalent routes for the administration of medications, playing a crucial role in the treatment and prevention of various diseases, including dental caries. Fluorides, employed as a preventive and control measure against dental caries, are available in two primary forms: Systemic fluorides and topical fluorides. Topical fluorides are found in toothpaste, varnish, gels, mouth rinses, and washes, while systemic fluorides are administered via lozenges, tablets, and liquid formulations. : This literature work focuses on the specific challenges associated with fluoride supplement formulations and aims to shed light on potential setbacks. Among these challenges, poor patient compliance, especially in pediatric populations, and the associated risk of underdosing or overdosing, leading to fluorosis, stand out as significant concerns. If left unaddressed, these issues could compromise the efficacy of one of the most effective caries prevention methods available. : The primary objective of this study is to explore advancements in fluoride supplement formulations, with a particular emphasis on addressing the identified challenges, especially for pediatric and geriatric patients. By devising improved formulations tailored to the unique needs of these populations, we aim to mitigate compliance issues and minimize the associated risk factors, thereby strengthening the effectiveness of dental caries prevention strategies. This research endeavors to contribute valuable insights to the field of oral healthcare and pharmaceutical development, ultimately promoting better oral health outcomes for individuals of all ages.

Oral Administration of a Specific p300/CBP Lysine Acetyltransferase Activator Induces Synaptic Plasticity and Repairs Spinal Cord Injury.

TTK21 is a small-molecule activator of p300/creb binding protein (CBP) acetyltransferase activity, which, upon conjugation with a glucose-derived carbon nanosphere (CSP), can efficiently cross the blood-brain barrier and activate histone acetylation in the brain. Its role in adult neurogenesis and retention of long-term spatial memory following intraperitoneal (IP) administration is well established. In this study, we successfully demonstrate that CSP-TTK21 can be effectively administered via oral gavage. Using a combination of molecular biology, microscopy, and electrophysiological techniques, we systematically investigate the comparative efficacy of oral administration of CSP and CSP-TTK21 in wild-type mice and evaluate their functional effects in comparison to intraperitoneal (IP) administration. Our findings indicate that CSP-TTK21, when administered orally, induces long-term potentiation in the hippocampus without significantly altering basal synaptic transmission, a response comparable to that achieved through IP injection. Remarkably, in a spinal cord injury model, oral administration of CSP-TTK21 exhibits efficacy equivalent to that of IP administration. Furthermore, our research demonstrates that oral delivery of CSP-TTK21 leads to improvements in motor function, histone acetylation dynamics, and increased expression of regeneration-associated genes (RAGs) in a spinal injury rat model, mirroring the effectiveness of IP administration. Importantly, no toxic and mutagenic effects of CSP-TTK21 are observed at a maximum tolerated dose of 1 g/kg in Sprague-Dawley (SD) rats via the oral route. Collectively, these results underscore the potential utility of CSP as an oral drug delivery system, particularly for targeting the neural system.

Tailored design of pH-responsive microbeads for oral delivery of lactoferrin nanotherapeutics of colon cancer

Colorectal cancer, one of the most fatal cancer types, has an unmet need for the development of targeted oral therapeutics. To address this, we propose to engineer a multiparticulate system to enhance the efficacy of anticancer drugs for treatment of colon cancer. We have developed a dual ligand- and pH-responsive multiparticulate system for oral drug delivery to the colon. Indomethacin (IND) and quercetin (QCT) preformulated as nanosuspensions (NSps) or liquid crystalline nanoparticles (LCNPs), respectively, were co-encapsulated into pH-responsive CA/HEC-MBs microbeads via ionoptropic gelation. To enhance tumor targeting, both nanoparticles were further coated with lactoferrin (Lf), which allows binding with Lf receptors on cancerous HCT-116 cells, resulting in higher internalization and superior cytotoxicity. Among various simulated gastrointestinal fluids, the engineered CA/HEC-MBs incorporating nanoparticles successfully released the drugs only in the colon (pH 6.8). Oral administration of both LF-targeted nanostructured microbeads into DMH-induced colorectal cancer bearing mice revealed superior in vivo anti-tumor efficacy. The microbeads efficiently reduced CEA and PCNA protein levels as well as the serum levels of IL-6, IL-1, and TNF-α. Apoptosis was also upregulated, as evidenced by increased Bax/Bcl2 ratio and increased expression levels of activated caspase-3 and caspase-9. Overall, these findings suggest that orally administered LF-targeted nanoparticle-based MBs for co-delivery of QCT and IND represent a promising alternative to conventional colon cancer therapy.

Risperidone/cyclodextrin inclusion complex electrospun nanofibers for fast-disintegrating antipsychotic drug delivery

In this paper, the inclusion complexes (ICs) of hydroxypropyl-beta-cyclodextrin (HPβCD) and risperidone were electrospun into nanofibrous film for potential fast-disintegrating drug delivery system. Risperidone is used to treat bipolar disorder, schizophrenia, and mood swings from autism. However, it is practically insoluble in aqueous medium. On the other hand, the encapsulation of risperidone into HPβCD cavity by inclusion complexation can enhance water solubility of this drug molecule. Here, the IC systems were prepared with 4/1 and 2/1 M ratio (HPβCD/risperidone). The highly concentrated HPβCD aqueous solutions (200 %, w/v) were used for the fiber formation. Finally, the system having 4/1 M ratio resulted in a clear and homogeneous solution showing that the HPβCD and risperidone completely formed IC. However, HPβCD/risperidone-IC having 2/1 M ratio was turbid and contained some small clumps of un-complexed risperidone. Even so, free-standing and thin nanofibrous films were obtained for both systems with an average fiber diameter of ∼315 nm and ∼280 nm for 2/1 and 4/1 systems, respectively. Both HPβCD/risperidone-IC nanofibers were produced with approximately 100 % preservation of risperidone within the nanofiber matrix without the loss of risperidone during electrospinning process, that is, HPβCD/risperidone-IC nanofibers retained the initial M ratio of 2/1 and 4/1 as in electrospinning solution. Both HPβCD/risperidone-IC nanofibrous films showed fast-disintegration and fast-release characteristics in artificial saliva and aqueous medium verifying their potential as a fast-disintegrating oral drug delivery system for risperidone.

Fast dissolving tablet

Fast dissolving tablets have emerged as a popular dosage form, particularly beneficial for pediatric and geriatric patients facing challenges such as dysphagia or hand tremors. These tablets dissolve quickly in saliva without needing water, enhancing compliance and effectiveness of therapy. They offer advantages like easy portability, accurate dosing, and improved bioavailability. Various technologies, including spray drying and melt granulation, have been developed for their manufacturing. This review provides comprehensive information on fast dissolving tablets, covering their definition, advantages, limitations, challenges, and available formulations. The design of an oral drug delivery system prioritizes convenience in administration and improved patient compliance, making it the preferred route of drug delivery despite certain drawbacks. Over the last decade, there has been a growing demand for Fast Disintegrating Tablets (FDTS), turning this field into a rapidly expanding area within the pharmaceutical industry. The formulation’s popularity and effectiveness have led to the development of various FDT technologies. These technologies aim to achieve rapid tablet disintegration and mouth dissolution within five seconds, eliminating the need for chewing or water intake. This characteristic is particularly advantageous for populations such as pediatrics, geriatrics, and patients facing difficulties in swallowing conventional tablets and capsules. The formulation of an easily administrable dosage form, considering challenges like swallowing difficulties and low patient compliance, has driven the creation of orally disintegrating tablets. Traditional preparation methods include spray drying, freeze drying, direct compression, molding, and sublimation. In addition, new technologies have been devised to enhance the production of orodispersible tablets.

Current Update of Clinical Therapeutic Strategies for Colon-Targeted Delivery Systems

Oral colon-targeted drug delivery systems represent a significant advancement offering both systemic and local therapeutic effects for a range of intestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, colonic bacterial infections, and colorectal cancer. These systems facilitate the delivery of both small molecules and macromolecular compounds such as peptides, proteins, antibodies, oligonucleotides, RNA, and probiotics. This review provides an up-to-date exploration of the critical factors crucial for the effective design and development of drug delivery systems targeting the colon. The chosen strategy takes into account various aspects of colon physiology that influences the profile of drug release, absorption, dissolution, and stability in the colon, including pH, retention time, presence of enzymes, pressure, presence of reactive oxygen species due to inflammation, and specific receptors. Site-targeted drug release allows for high concentrations in the colon while minimizing systemic adverse effects by reducing or preventing drug absorption in the small intestine.

Review of Extended Drug Delivery Oral Formulations

Generally maximum times applied route for administration of drugs is oral only. The drugs that are given orally but are having smaller half-life and great dosing rate of recurrence are very promising methodology is oral extended release drug delivery system. In this system, frequency of dosing diminishes or moderates for assured drugs through slow release of drug over an extended time period. Extended release drug delivery system can affect by different physicochemical and biological properties. The present review contains brief–up on innumerable oral extended release formulation methodologies.

Development and Characterization Pioglitazone Hydrochloride Loaded Nanoparticle for Management of Diabetes Mellitus

The potential applications of nanoparticles as oral drug delivery systems for diabetes treatment are discussed in this research article. This paper discusses polymeric nanoparticles, polysaccharides, and polymeric nanoparticles in the oral administration of anti-diabetic drugs. Diabetes is a chronic metabolic disorder characterized by insulin deficiency. Diabetes treatments are numerous, and nanoparticles have several advantages. Several studies and research reports based on nanotechnological approaches in the formulation of anti-diabetic drugs have highlighted the fact that research in the formulation of nanodrugs improved diabetes-fighting strategies based on plausible molecular mechanisms of action of the drugs. Additionally, efforts have been made to determine the optimal drug concentration and time of exposure in order to recommend a scientifically validated drug dose response in the development of various therapeutic strategies for anti-diabetic drugs, various types of nanoparticles are available; polymeric nanoparticles are one of the most commonly used nanoparticles. Polymeric nanoparticles range in size from 10-1000 nm. Polymeric nanoparticles created by combining a drug and a polymer. The main advantages of polymeric nanoparticles are their ease of preparation, targeted delivery, dose minimization, and high therapeutic efficiency.

Methacrylic Acid Co-Polymers: Crucial agents for the Colon Targeted Oral Drug Delivery System

The objective of this research was to formulate an Ornidazole tablet capable of delivering the drug intact to the colon for the treatment of IBD, ulcerative colitis, and Crohn's disease. In the current investigation, pH-independent and pH-dependent polymers were used to target the Ornidazole tablet to the colon. This study evaluated two time-dependent (sustained release) polymers (Eudragit RS and Eudragit RL) and one pH-dependent polymer (Eudragit S100). The influence of the two formulation variables of the colon drug delivery system on the two response variables were examined simultaneously using a statistical 32-Full factorial design. X1 Ratio of Eudragit RS 100 to Eudragit RL 100 and X2 % weight gain with Eudragit S 100 were treated as independent variables in a factorial design, while Y5 and Y12 were treated as dependent variables. Through this procedure, a total of nine F9 samples were produced. Y5 in-vitro release should not exceed 10%, whereas Y12 should surpass 85%. Based on these results, batch B8 is considered the finest of all cohorts. According to the results, the enhanced formulation provides optimal intact drug delivery to the targeted region.

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.