Local Drug Delivery Research Articles

Effect of Ocimum sanctum L as LDD in periodontal therapy.

Ocimum sanctum L (Tulsi) has various properties like antibacterial, anti-inflammatory and anti-oxidant. To compare the effect of the local-drug delivery system containing 2% Ocimum sanctum L (Tulsi) as an adjunct to scaling and root planing (SRP).The main aim of the study was to evaluate the efficacy of Ocimum sanctum L (Tulsi) gel with Tetracycline fibers (Actisite) for the treatment of periodontitis patients. 40 subjects with periodontitis (pocket depth of 5 mm) were selected and divided into 2 groups Group I: Ocimum sanctum L (Tulsi) gel (n= 20) and Group II: Tetracycline fibers (Actisite) (n = 20). Clinical parameters assessed were Gingival Index , Plaque Index , Probing Depth and Clinical Attachment Loss were assessed at baseline, 1 month, 3 months, 6 months, 8 months. Our results showed that Gingival index and Plaque index for for GROUP I: Ocimum sanctum L (Tulsi) and GROUP II: Tetracycline fibers (Actisite)are not statistically significant p>0.05 for baseline, at 1 month, 3 months, 6 months, 8 months. Probing depth and Clinical attachment are not significant p>0.05 for baseline, at 1 month, 3 months, 6 months, and statistically significant difference seen at 8 months p<0.05. 2% Ocimum sanctum L (Tulsi) gel can be effectively used as an adjunct to scaling and root planing. When used as an adjunct to scaling and root planing, it helps in reduction of pocket depth and gain of clinical attachment. Ocimum sanctum L (Tulsi) showed promising results when compared to Tetracycline fibers (Actisite).

Dual-drug loaded ultrasound-responsive nanodroplets for on-demand combination chemotherapy

Phase-changing nanodroplets are nanometric sized constructs that can be vaporized via external stimuli, such as focused ultrasound, to generate gaseous bubbles that are visible in ultrasound. Their activation can also be leveraged to release their payload, creating a method for ultrasound-modulated localized drug delivery. Here, we develop a perfluoropentane core nanodroplet that can simultaneously load paclitaxel and doxorubicin, and release them in response to an acoustic trigger. A double emulsion method is used to incorporate the two drugs with different physio-chemical properties, which allows for a combinatorial chemotherapy regimen to be used. Their loading, release, and biological effects on a triple negative breast cancer mouse model are investigated. We show that activation enhances the drug-delivery effect and delays the tumor growth rate in vivo. Overall, the phase-changing nanodroplets are a useful platform to allow on-demand delivery of combinations of drugs.

Comparative Assessment of the Effect of Three Various Local Drug Delivery Medicaments in the Management of Chronic Periodontitis.

The aim of this study was to evaluate the efficacy of three different local drug delivery medications in the treatment of chronic periodontitis. Sixty participants, aged 30-55 years, were involved in the current research. Participants who fulfilled the inclusion criteria entered the study and were allocated at random to one of the three groups, each comprising 20 patients as: group A: Scaling and root planing (SRP) with local application of doxycycline gel, group B: SRP with local application of tetracycline fibers, and group C: SRP with local application of chlorhexidine gel. The plaque index (PI), the gingival index (GI), and periodontal pocket depth (PPD) were documented at baseline visit (prior to local drug delivery), and these indices were again documented 30 and 90 days post-local drug delivery. At baseline, GI score for doxycycline gel use decreased from 1.38 ± 0.05 to 0.94 ± 0.02, 1.36 ± 0.11 to 0.76 ± 0.19 for tetracycline fibers use, as well as from 1.38 ± 0.10 to 0.84 ± 0.21 for chlorhexidine gel use post 90 days. The PI value at baseline for doxycycline gel use lessened from 1.26 ± 0.01 to 1.02 ± 0.06, 1.30 ± 0.14 to 0.82 ± 0.16 for tetracycline fibers use, as well as 1.30 ± 0.22 to 0.98 ± 0.11 for chlorhexidine gel use post 90 days. At baseline, PPD values for doxycycline gel use decreased from 5.88 ± 0.24 to 3.72 ± 0.11, tetracycline fibers use lessened from 5.90 ± 0.09 to 3.02 ± 0.06, as well as for chlorhexidine gel group from 5.82 ± 0.18 to 3.44 ± 0.16 post 90 days. Within the limitations of the current research, it may be inferred that tetracycline fibers exhibited somewhat superior enhancement to chlorhexidine as well as doxycycline gel. Local administration of antibacterial agents in continued or regulated delivery arrangement is employed to augment the actions of nonsurgical periodontal management, and it may be likely to attain gingival well-being by eliminating the requirement for invasive methods with the aid of local drug delivery arrangements. Chosen elimination or prohibition of microbial pathogens with locally administered antibacterial agents coupled with SRP is an efficient move toward treatment of chronic periodontitis.

Novel Collagen Surgical Patches for Local Delivery of Multiple Drugs.

Effective control of post-operative inflammation after tissue repair remains a clinical challenge. A tissue repair patch that could appropriately integrate into the surrounding tissue and control inflammatory responses would improve tissue healing. A collagen-based hybrid tissue repair patch has been developed in this work for the local delivery of an anti-inflammatory drug. Dexamethasone (DEX) was encapsulated into PLGA microspheres and then co-electrocompacted into a collagen membrane. Using a simple process, multiple drugs can be loaded into and released from this hybrid composite material simultaneously, and the ratio between each drug is controllable. Anti-inflammatory DEX and the anti-epileptic phenytoin (PHT) were co-encapsulated and released to validate the dual drug delivery ability of this versatile composite material. Furthermore, the Young's modulus of this drug-loaded collagen patch was increased to 20 KPa using a biocompatible riboflavin (vitamin B2)-induced UV light cross-linking strategy. This versatile composite material has a wide range of potential applications which deserve exploration in further research.

Less Is More: Developments in Nanotechnology for Antirestenosis Therapies.

Despite recent advancements in vascular disease treatments, thrombosis and poor long-term vessel patency remain significant barriers to effective endovascular intervention. Current balloon angioplasty and stenting techniques effectively restore acute blood flow in occluded vessels but have persistent limitations. Damage to the arterial endothelium caused by injury during catheter tracking triggers neointimal hyperplasia and the release of proinflammatory factors leading to increased risk of thrombosis and restenosis. Antirestenotic agents commonly delivered on angioplasty balloons and stents have lowered arterial restenosis rates, but the absence of cell type selectivity significantly delays critical endothelium repair. Targeted delivery of biomolecular therapeutics, coupled with engineered nanoscale excipients, has the potential to redefine cardiovascular interventions by improving long-term efficacy, limiting off-target effects, and reducing costs compared with conventional clinical standards of care. This review analyzes current forms of localized vascular drug delivery, emerging nanoscale therapeutic and excipient strategies, and provides recommendations for future areas of study to advance the treatment of vascular disease through innovations in nanotechnology.

Establishment of a Rodent Glioblastoma Partial Resection Model for Chemotherapy by Local Drug Carriers—Sharing Experience

Local drug delivery systems (LDDS) represent a promising therapy strategy concerning the most common and malignant primary brain tumor glioblastoma (GBM). Nevertheless, to date, only a few systems have been clinically applied, and their success is very limited. Still, numerous new LDDS approaches are currently being developed. Here, (partial resection) GBM animal models play a key role, as such models are needed to evaluate the therapy prior to any human application. However, such models are complex to establish, and only a few reports detail the process. Here, we report our results of establishing a partial resection glioma model in rats suitable for evaluating LDDS. C6-bearing Wistar rats and U87MG-spheroids- and patient-derived glioma stem-like cells-bearing athymic rats underwent tumor resection followed by the implantation of an exemplary LDDS. Inoculation, tumor growth, residual tumor tissue, and GBM recurrence were reliably imaged using high-resolution Magnetic Resonance Imaging. The release from an exemplary LDDS was verified in vitro and in vivo using Fluorescence Molecular Tomography. The presented GBM partial resection model appears to be well suited to determine the efficiency of LDDS. By sharing our expertise, we intend to provide a powerful tool for the future testing of these very promising systems, paving their way into clinical application.

A novel cerasomal gallic acid as a non-ulcerogenic agent with an improved anti-inflammatory potential

In order to treat inflammatory bowel disease (IBD), there is an attempt to develop local drug delivery systems. The use of bioactive compounds such as gallic acid (GA) in a precise colon-targeting drug delivery platform is expected to enhance its bioavailability and increase local therapeutic responses. In this study, a novel cerasome-forming lipid (CFL) containing organosilane-based oleic acid was mixed with 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine via one-step construction to prepare composite cerasomes by varying mole ratios. The physicochemical properties, drug-loading capacity, long-term storage stability, and release rates of (GA) from cerasomes have been investigated. The size of cerasomal gallic acid (CG) was about 319 nm with −23 mV surface charge and 77% drug sustained released after 140 h in the simulated gastrointestinal fluids. Composite vesicles consisting of DPPC and CFL with a 1:1 M ratio exhibited good cytocompatibility and cellular uptake, also, the released gallic acid effectively inhibit the reactive species in LPS-induced inflammation of Caco-2 cells, compared to free (GA). Our results indicate that this novel CG has great potential to be applied as a non-ulcerogenic agent due to the prolonging duration of action in IBD therapy.

Encapsulation of β-NGF in injectable microrods for localized delivery accelerates endochondral fracture repair.

Introduction: Currently, there are no non-surgical FDA-approved biological approaches to accelerate fracture repair. Injectable therapies designed to stimulate bone healing represent an exciting alternative to surgically implanted biologics, however, the translation of effective osteoinductive therapies remains challenging due to the need for safe and effective drug delivery. Hydrogel-based microparticle platforms may be a clinically relevant solution to create controlled and localized drug delivery to treat bone fractures. Here, we describe poly (ethylene glycol) dimethacrylate (PEGDMA)-based microparticles, in the shape of microrods, loaded with beta nerve growth factor (β-NGF) for the purpose of promoting fracture repair. Methods: Herein, PEGDMA microrods were fabricated through photolithography. PEGDMA microrods were loaded with β-NGF and in vitro release was examined. Subsequently, bioactivity assays were evaluated in vitro using the TF-1 tyrosine receptor kinase A (Trk-A) expressing cell line. Finally, in vivo studies using our well-established murine tibia fracture model were performed and a single injection of the β-NGF loaded PEGDMA microrods, non-loaded PEGDMA microrods, or soluble β-NGF was administered to assess the extent of fracture healing using Micro-computed tomography (µCT) and histomorphometry. Results: In vitro release studies showed there is significant retention of protein within the polymer matrix over 168 hours through physiochemical interactions. Bioactivity of protein post-loading was confirmed with the TF-1 cell line. In vivo studies using our murine tibia fracture model show that PEGDMA microrods injected at the site of fracture remained adjacent to the callus for over 7 days. Importantly, a single injection of β-NGF loaded PEGDMA microrods resulted in improved fracture healing as indicated by a significant increase in the percent bone in the fracture callus, trabecular connective density, and bone mineral density relative to soluble β-NGF control indicating improved drug retention within the tissue. The concomitant decrease in cartilage fraction supports our prior work showing that β-NGF promotes endochondral conversion of cartilage to bone to accelerate healing. Discussion: We demonstrate a novel and translational method wherein β-NGF can be encapsulated within PEGDMA microrods for local delivery and that β-NGF bioactivity is maintained resulting in improved bone fracture repair.

Electrophoretic deposition of gentamicin and chitosan into titanium nanotubes to target periprosthetic joint infection.

Periprosthetic joint infection (PJI) occurs in 1%-2% of primary total hip and knee arthroplasties; the rate can reach 20% in individuals at risk. Due to the low local bioavailability of systemic antibiotics and possible off-target effects, localized drug delivery systems are of great importance. Our aim was the electrophoretic deposition (EPD) of gentamicin and chitosan in Titanium (Ti) nanotubes to establish a local, prolonged antibiotic delivery. Nanotubes were created on Ti wire with a two-step anodization process. For drug deposition, EPD and the air-dry methods were compared. For a prolonged drug release, gentamicin and crosslinked chitosan were deposited in a two-step EPD process. Drug release was quantified by fractional volume sampling. The Ti wires were tested against Staphylococcus aureus by agar dilution and liquid culture methods. MC3T3-E1 osteoblastic cell viability was determined with trypan blue. Nanotubes were characterized by a 100 nm diameter and 7 μm length. EPD allowed a higher amount of gentamicin deposited than the air-dry method. Drug deposition was controllable by adjusting the voltage and duration of the EPD process. The crosslinked chitosan layer allowed diffusion-driven release kinetics for up to 3 days. Gentamicin-loaded Ti wires significantly inhibited bacterial growth and resulted in a larger inhibition zone compared to unloaded wires. Twenty-four hours of incubation with loaded wires did not have a significant effect on osteoblast viability. Gentamicin-loaded Ti nanotubes represent a promising approach for PJI prevention, as well as a valuable preclinical tool for the investigation of localized drug delivery systems created on Ti surface.

In situ Hydrogels Prepared by Photo-initiated Crosslinking of Acrylated Polymers for Local Delivery of Antitumor Drugs

A triblock copolymer was synthesized by ring opening polymerization of ε‐caprolactone in the presence of poly(ethylene glycol) (PEG). The resulted PCL-PEG-PCL triblock copolymer, PEG and monomethoxy (MPEG) were functionalized by end group acrylation. NMR and FT-IR analyses evidenced the successful synthesis and functionalization of polymers. A series of photo-crosslinked hydrogels composed of acrylated PEG-PCL-Acr and MPEG-Acr or PEG-Acr were prepared by exposure to visible light using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as initiator. The hydrogels present a porous and interconnected structure as shown by SEM. The swelling performance of hydrogels is closely related to the crosslinking density and hydrophilic content. Addition of MPEG or PEG results in increase in water absorption capacity of hydrogels. In vitro degradation of hydrogels was realized in the presence of a lipase from porcine pancreas. Various degradation rates were obtained which mainly depend on the hydrogel composition. MTT assay confirmed the good biocompatibility of hydrogels. Importantly, in situ gelation was achieved by irradiation of a precursor solution injected in the abdomen of mice. Doxorubicin (DOX) was selected as a model antitumor drug to evaluate the potential of hydrogels in cancer therapy. Drug-loaded hydrogels were prepared by in situ encapsulation. In vitro drug release studies showed a sustained release during 28 days with small burst release. DOX-loaded hydrogels exhibit antitumor activity against A529 lung cancer cells comparable to free drug, suggesting that injectable in situ hydrogel with tunable properties could be most promising for local drug delivery in cancer therapy.

A dual functional polypeptide with antibacterial and anti-inflammatory properties for the treatment of periodontitis

Periodontitis has been reported as the sixth most prevalent disease in human beings. This destructive disease is closely related to systemic diseases. Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and drug resistance. Inspired by the pathogenesis of periodontitis, we implemented a strategy to construct a dual functional polypeptide LL37-C15, which exhibited remarkable antibacterial effect against P. gingivalis and A. actinomycetemcomitans. In addition, LL37-C15 inhibits the release of pro-inflammatory cytokines by controlling the inflammatory pathway and reversing macrophage M1. Furthermore, the anti-inflammatory effect of LL37-C15 was also verified in vivo in a periodontitis rat model through the morphometry and histological observations of alveolar bone, hematoxylin-eosin, and Trap staining in gingival tissue. The results of molecular dynamics simulations showed that LL37-C15 could selectively destroy the bacterial cell membrane and protect the animal cell membrane in a self-destructive manner. The results showed that the polypeptide LL37-C15, as a novel promising therapeutic agent, exhibited a great potential for the periodontitis management. What's more, this dual functional polypeptide provides a promising strategy for building a multifunctional therapeutic platform against the inflammation and other diseases.

Osteogenesis promotion by injectable methacryloylated gelatin containing psoralen and its bacteriostatic properties.

The treatment of periodontitis focuses on controlling the progression of inflammation, reducing plaque accumulation, and promoting bone tissue reconstruction. Among them, the reconstruction of irregular bone resorption caused by periodontitis is a long-standing challenge. At present, the local drug treatment of periodontitis is mainly anti-inflammatory and antibacterial drugs. In this study, psoralen (Pso), a Chinese herbal medicine with anti-inflammatory, antibacterial, and osteogenic effects, was selected for the local treatment of periodontitis. Meanwhile, an injectable methacrylate gelatin (GelMA) platform loading with Pso was constructed. Pso-GelMA had the properties of fluidity, light cohesion, self-healing, and slow release, which could be better used in the deep and narrow structure of the periodontal pocket, and greatly increased the effectiveness of local drug delivery. The pore size of Gelma hydrogel did not change after loading Pso by SEM. In vitro, Pso-GelMA effectively upregulated the expression of osteogenic genes and proteins, increased alkaline phosphatase activity, promoted the mineralisation of rat bone marrow mesenchymal stem cells (BMSCs) extracellular matrix, and had significant antibacterial effects on Staphylococcus aureus and Fusobacterium nucleatum. Therefore, Pso-GelMA has immense promise in the adjuvant treatment of periodontitis.

Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices.

Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications.

Effective Treatment of Haemophilus influenzae-Induced Bacterial Conjunctivitis by a Bioadhesive Nanoparticle Reticulate Structure

Ocular formulations should provide an effective antibiotic concentration at the site of infection to treat bacterial eye infections. However, tears and frequent blinking accelerate the drug clearance rate and limit drug residence time on the ocular surface. This study describes a biological adhesion reticulate structure (BNP/CA-PEG) consisting of antibiotic-loaded bioadhesion nanoparticles (BNP/CA), with an average 500-600 nm diameter, and eight-arm NH2-PEG-NH2 for local and extended ocular drug delivery. This retention-prolonging effect is a function of the Schiff base reaction between groups on the surface of BNP and amidogen on PEG. BNP/CA-PEG showed significantly higher adhesion properties and better treatment efficacy in an ocular rat model with conjunctivitis in comparison to non-adhesive nanoparticles, BNP, or free antibiotics. Both in vivo safety experiment and in vitro cytotoxicity test verified the biocompatibility and biosafety of the biological adhesion reticulate structure, indicating a promising translational prospect for further clinical use.

"Combo" Multi-Target Pharmacological Therapy and New Formulations to Reduce Inflammation and Improve Endogenous Remyelination in Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is characterized by a cascade of events that lead to sensory and motor disabilities. To date, this condition is irreversible, and no cure exists. To improve myelin repair and limit secondary degeneration, we developed a multitherapy based on nanomedicines (NMeds) loaded with the promyelinating agent triiodothyronine (T3), used in combination with systemic ibuprofen and mouse nerve growth factor (mNGF). Poly-L-lactic-co-glycolic acid (PLGA) NMeds were optimized and loaded with T3 to promote sustained release. In vitro experiments confirmed the efficacy of T3-NMeds to differentiate oligodendrocyte precursor cells. In vivo rat experiments were performed in contusion SCI to explore the NMed biodistribution and efficacy of combo drugs at short- and long-term post-lesion. A strong anti-inflammatory effect was observed in the short term with a reduction of type M1 microglia and glutamate levels, but with a subsequent increase of TREM2. In the long term, an improvement of myelination in NG2-IR, an increase in MBP content, and a reduction of the demyelination area were observed. These data demonstrated that NMeds can successfully be used to obtain more controlled local drug delivery and that this multiple treatment could be effective in improving the outcome of SCIs.

New Methacrylated Biopolymer-Based Hydrogels as Localized Drug Delivery Systems in Skin Cancer Therapy.

The aim of the present work was to obtain drug-loaded hydrogels based on combinations of dextran, chitosan/gelatin/xanthan, and poly (acrylamide) as a sustained and controlled release vehicle of Doxorubicin, a drug used in skin cancer therapy that is associated with severe side effects. Hydrogels for use as 3D hydrophilic networks with good manipulation characteristics were produced using methacrylated biopolymer derivatives and the methacrylate group's polymerization with synthetic monomers in the presence of a photo-initiator, under UV light stimulation (365 nm). Transformed infrared spectroscopy analysis (FT-IR) confirmed the hydrogels' network structure (natural-synthetic composition and photocrosslinking), while scanning electron microscopy (SEM) analysis confirmed the microporous morphology. The hydrogels are swellable in simulated biological fluids and the material's morphology regulates the swelling properties: the maximum swelling degree was obtained for dextran-chitosan-based hydrogels because of their higher porosity and pore distribution. The hydrogels are bioadhesive on a biological simulating membrane, and values for the force of detachment and work of adhesion are recommended for applications on skin tissue. The Doxorubicin was loaded into the hydrogels and the drug was released by diffusion for all the resulting hydrogels, with small contributions from the hydrogel networks' relaxation. Doxorubicin-loaded hydrogels are efficient on keratinocytes tumor cells, the sustained released drug interrupting the cells' division and inducing cell apoptosis; we recommend the obtained materials for the topical treatment of cutaneous squamous cell carcinoma.

Calcium phosphate bone cements as local drug delivery systems for bone cancer treatment.

Bone cancer is usually a metastatic disease, affecting people of all ages. Its effective therapy requires a targeted drug administration locally at the cancer site so that the surrounding healthy organs and tissues stay unharmed. Upon a thorough literature search, a tremendous number of published articles are reporting on development of calcium phosphate cements (CPCs) for the treatment of a variety of diseases, such as osteoporosis, osteoarthritis, osteomyelitis, and other musculoskeletal disorders. However, just a limited number of research employs CPCs specifically for bone cancer treatment. In this review article, we study the factors influencing the local drug release from CPCs and particularly focus on bone cancer therapy. Finally, we locate the deficiencies in the literature regarding this specific topic and propose which other perspectives should be considered and discussed in future articles.

Local drug delivery systems for the inner ear

Abstract Objectives Recent advancements in molecular biology have led to a better understanding of the mechanisms associated with sensorineural hearing loss and other inner ear diseases. These developments offer hope for new treatment approaches benefiting millions of patients. However, drug therapy for the cochlea presents significant challenges, necessitating the development of innovative technologies to ensure safe and effective delivery of therapeutic compounds. Among these emerging technologies, microfluidic-based delivery systems are gaining attention as a promising method for direct intracochlear administration. Ultimately, these systems have the potential to provide sustained release of regenerative compounds, thereby restoring hearing in patients suffering from various auditory conditions. Key findings This article provides a comprehensive review of recent progress in the field of intracochlear drug delivery systems. In addition, the review encompasses passive systems, such as osmotic pumps, as well as active microfluidic devices. Moreover, the article discusses the integration of these delivery systems with existing cochlear implants. The primary objective is to offer a concise overview of the current state of development for intracochlear drug delivery systems, which can be combined with emerging therapeutic compounds to effectively treat inner ear diseases. Conclusions The safe and effective treatment of auditory diseases requires the development of microscale delivery devices capable of extended operation and direct application to the inner ear. To achieve this, significant advancements in miniaturization and integration of multiple functions are necessary. These functions include drug storage, delivery, power management, and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for the treatment of these diseases.

β-Glucan and Fatty Acid Based Mucoadhesive Carrier for Gastrointestinal Tract Specific Local and Sustained Drug Delivery.

The oral route is considered the most convenient route of drug administration for both systemic and local delivery. Besides stability and transportation, another unmet but important issue regarding oral medication is retention duration within the specific region of the gastrointestinal (GI) tract. We hypothesize that an oral vehicle that can adhere and maintain retention within the stomach for a longer duration can be more effective to treat stomach-related diseases. Therefore, in this project, we developed a carrier that is highly specific to the stomach and maintains its retention for a longer duration. We developed a vehicle composed of β-Glucan And Docosahexaenoic Acid (GADA) to observe its affinity and specificity to the stomach. GADA forms a spherical-shaped particle with negative zeta potential values that vary based on the feed ratio of docosahexaenoic acid. Docosahexaenoic acid is an omega-3 fatty acid that has transporters and receptors throughout the GI tract, such as CD36, plasma membrane-associated fatty acid-binding protein (FABP (pm)), and a family of fatty acid transport proteins (FATP1-6). The in vitro studies and characterization data showed that GADA has the capability to carry a payload of hydrophobic molecules and specifically deliver the payload to the GI tract, exert its therapeutic effects, and help to maintain stability for more than 12 h in the gastric and intestinal fluid. The particle size and surface plasmon resonance (SPR) data showed that GADA has a strong binding affinity with mucin in the presence of simulated gastric fluids. We observed a comparatively higher drug release of lidocaine in gastric juice than that in intestinal fluids, demonstrating the influence of the pH values of the media on drug-release kinetics. In vivo and ex vivo imaging of mice demonstrated that GADA maintains its retention within the stomach for at least 4 hr. This stomach-specific oral vehicle holds strong promise to translate various injectable therapeutic drugs to oral form upon further optimizations.

Rational Design of Bioactive Hydrogels toward Periodontal Delivery: From Pathophysiology to Therapeutic Applications

AbstractPeriodontitis is a biofilm‐induced, host‐mediated inflammatory disease that results in periodontal tissue destruction. The design of functional biomaterials based on disease pathophysiology is essential for enhancing their therapeutic effects in periodontitis treatment. As promising localized drug delivery systems and tissue engineering scaffolds, hydrogels have gained significant interest for controlled and sustained release of bioactive agents in periodontal applications. The rational design of bioactive hydrogels can facilitate bacterial control and modulate destructive host inflammation, thereby preventing the progression of periodontitis. In this review, the pathophysiological mechanisms underlying periodontitis as fundamental principles for the design of functional hydrogel systems are first introduced. In the following part, an overview is systematically provided of the types and functions of the bioactive hydrogel systems loaded with anti‐bacterial and anti‐inflammatory agents for periodontal delivery. Finally, the remaining challenges and future perspectives of hydrogel delivery systems for periodontal applications are proposed. It is believed that this review will inspire the rational design and development of innovative functional hydrogel biomaterials toward periodontal therapy.