Local Drug Delivery System Research Articles

Titanium Implant Modified With Zinc-Doped Carbon Dot Layer as an Innovative Coating for the Development of Local Drug Delivery System for Ciprofloxacin.

This study presents a new innovative drug delivery system for ciprofloxacin, which is based on the formation of a zinc-doped carbon dots layer on the surface of a titanium alloy (TiAl4V6). In the study, the effectiveness of the synthesis method of a zinc-doped carbon dots layer was determined. The distribution of the layer of carbon dots on the surface of the titanium alloy was investigated using the FT-IR mapping technique, which confirmed the efficiency of the synthesis. The effective synthesis of carbon dots and the coordination of zinc ions on their surface opens the possibility of sorption of ciprofloxacin, which results in a high application potential of the obtained biomaterial. The introduction of zinc cations on the surface of the carbon dots layer resulted in high sorption results of the active substance (40 μg of drug per 1 cm2 of implant). The release profile of ciprofloxacin from the modified surface of the titanium alloy indicates that this active substance can be released for up to 4 h. The biomaterial obtained in this work is also hydrophilic (about 40°), which was shown by the contact angle tests. This is an important feature and indicates a high application potential of the performed modification. The resulting layer has antibacterial properties. Growth inhibition for microorganisms such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus cereus, and Candida albicans ranged from 74% to 96%. The creation of such a layer on the titanium alloy may reduce the risk of infection during the implantation procedure.

New Carrageenan/2-Dimethyl Aminoethyl Methacrylate/Gelatin/ZnO Nanocomposite as a Localized Drug Delivery System with Synergistic Biomedical Applications

In recent years, the development of multifunctional hydrogels has gained significant attention due to their potential in various biomedical applications, including antimicrobial, antioxidant, and anticancer therapies. By integrating biocompatible polymers and nanoparticles, these hydrogels can achieve enhanced activity and targeted therapeutic effects. In this study, carrageenan/2-dimethyl aminoethyl methacrylate/gelatin (CAR/DEMA/Gelt) composite hydrogel was synthesized using microwave radiation specifically for its efficiency in enhancing cross-linking and promoting uniform nanoparticle dispersion within the matrix. Zinc oxide (ZnO) nanoparticles were incorporated into the hydrogel to form the (CAR/DEMA/Gelt/ZnO) nanocomposite. The hydrogels were characterized using FT-IR, FE-SEM, XRD, TGA, and EDX, confirming successful cross-linking and structural integrity. The nanocomposite hydrogel exhibited more enhanced antimicrobial activity than the composite hydrogel against Gram-positive Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis), with inhibition zones of 15 mm and 16 mm, respectively, while in case of the Gram-negative bacteria, Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), the inhibition zones were 29 mm and 19 mm, respectively. In addition to the unicellular fungi, Candida albicans (C. albicans), the inhibition zone was 19 mm. Moreover, the nanocomposite showed anti-inflammatory activity comparable to those of Indomethacin and antioxidant activity, with an impressive IC50 value of 33.3 ± 0.05 µg/mL. In vitro cytotoxicity assays revealed significant anticancer activity. Against the MCF-7 breast cancer cell line, the CAR/DEMA/Gelt/ZnO nanocomposite showed 72.5 ± 0.02% cell viability, which decreased to 30.8 ± 0.01% after loading doxorubicin (DOX). Similarly, against the HepG2 liver cancer cell line, the free nanocomposite displayed 59.9 ± 0.006% cell viability, which depleted to 29.9 ± 0.005% when DOX was uploaded. This CAR/DEMA/Gelt/ZnO nanocomposite hydrogel demonstrates strong potential as a multifunctional platform for targeted biomedical applications, particularly in cancer therapy.

Efficacy of Scaling and Root Planing with and without Adjunctive Use of Diode Laser or 1% Ornidazole Gel as Local Drug Delivery in the Management of Chronic Periodontitis: An Experimental Study

Background: Chronic periodontitis is a prevalent inflammatory disease affecting the supporting structures of the teeth. Scaling and root planing (SRP) is a conventional non-surgical therapy. However, adjunctive treatments like diode lasers and local drug delivery systems (e.g., 1% Ornidazole gel) have been proposed to enhance treatment outcomes. This study aimed to assess the efficacy of SRP alone and combined with diode laser or 1% Ornidazole gel as adjunctive therapies for managing chronic periodontitis. Materials and Methods: This experimental study included forty five individuals of both gender aged between 27 and 60 years diagnosed with chronic periodontitis and having pocket depths >4 mm in different quadrants of the mouth were selected and divided equally into three groups as Group-I (treated with SRP only), Group-II (treated with SRP and diode Laser application of 1.5 w, 980nm,30sec continuous wave), Group-III (treated with SRP and Application of 1% Ornidazole gel, as local drug delivery). Clinical parameters including gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL) were recorded at baseline and after 1 month of treatment. Statistical analysis was performed to compare the outcomes among the three groups.Results: All groups exhibited significant improvement in periodontal health, with reductions in GI, PPD and improvements in CAL. The intra-group comparison of all three groups from baseline to one month showed a statistically significant reduction in GI, PPD and CAL. In contrast, the intergroup comparison between Group I (SRP only) and Group II (SRP+Diode laser) showed statistically non-significant results in PPD and CAL. A statistically significant reduction in PPD and CAL was observed in Group III (SRP+ 1% Ornidazole gel) compared to Group I and Group II.Conclusion: Adjunctive use of diode laser and 1% Ornidazole gel enhances the efficacy of SRP in treating chronic periodontitis. Both modalities offer clinical benefits over SRP alone, with the 1% ornidazole showing marginally better results. when used as an adjunct to scaling and root planing in non-surgical periodontal therapy of patients with chronic periodontitis. Further research with a larger sample size and longer follow-up is needed to validate these findings.

Current knowledge of vertebral osteomyelitis: a review.

As life expectancy increases worldwide, the elderly population in every country is growing in both the size and proportion. This review aims to provide a comprehensive overview of the microbiology, clinical presentation, diagnostic strategies, and therapeutic approaches to vertebral osteomyelitis, summarizing the latest evidence to guide effective treatment. A comprehensive literature search was conducted using the Medline and Embase databases to identify relevant studies on vertebral osteomyelitis. The search included the following keywords: "vertebral osteomyelitis," "spinal infection," "discitis," "spondylitis," " spondylodiscitis," and "spinal epidural abscess." Both retrospective and prospective studies, case series, and reviews were considered. This condition is commonly caused by bacteria such as Staphylococcus aureus or gram-negative bacilli, but can also be caused by other pathogens like fungi and parasites. The onset of vertebral osteomyelitis is insidious, with low specificity in clinical manifestations, often making early diagnosis difficult. Delayed or inadequate treatment may lead to sepsis, permanent neurological damage, or even death. Treatment strategies emphasize the importance of identifying the causative pathogen to guide effective antimicrobial therapy. Current consensus does not advocate for empirical antibiotic treatment unless patients exhibit signs of neurological impairment or severe sepsis. Severe cases involving neurological paralysis, spinal instability, or sepsis may require surgical intervention. Vertebral osteomyelitis requires prompt diagnosis and treatment for a good prognosis. Delayed diagnosis and treatment can lead to permanent neurological deficits or death. Identifying the causative organism is crucial for guiding appropriate antimicrobial therapy. In addition to conservative and surgical treatments, local drug delivery systems offer new approaches to managing spinal osteomyelitis.

Prospective and challenges of locally applied repurposed pharmaceuticals for periodontal tissue regeneration.

Periodontitis is a persistent inflammatory condition that causes periodontal ligament degradation, periodontal pocket development, and alveolar bone destruction, all of which lead to the breakdown of the teeth's supporting system. Periodontitis is triggered by the accumulation of various microflora (especially anaerobes) in the pockets, which release toxic substances and digestive enzymes and stimulate the immune system. Periodontitis can be efficiently treated using a variety of techniques, both regional and systemic. Effective therapy is dependent on lowering microbial biofilm, minimizing or eradicating pockets. Nowadays, using local drug delivery systems (LDDSs) as an adjuvant therapy to phase I periodontal therapy is an attractive option since it controls drug release, resulting in improved efficacy and lesser adverse reactions. Choosing the right bioactive agent and mode of delivery is the foundation of an efficient periodontal disease management approach. The objective of this paper is to shed light on the issue of successful periodontal regeneration, the drawbacks of currently implemented interventions, and describe the potential of locally delivered repurposed drugs in periodontal tissue regeneration. Because of the multiple etiology of periodontitis, patients must get customized treatment with the primary goal of infection control. Yet, it is not always successful to replace the lost tissues, and it becomes more challenging as the defect gets worse. Pharmaceutical repurposing offers a viable, economical, and safe alternative for non-invasive, and predictable periodontal regeneration. This article clears the way in front of researchers, decision-makers, and pharmaceutical companies to explore the potential, effectiveness, and efficiency of the repurposed pharmaceuticals to generate more economical, effective, and safe topical pharmaceutical preparations for periodontal tissue regeneration.

Intrinsic PD-L1 Degradation Induced by a Novel Self-Assembling Hexapeptide for Enhanced Cancer Immunotherapy.

Programmed death-ligand 1 (PD-L1) is a critical immune checkpoint protein that facilitates tumor immune evasion. While antibody-based PD-1/PD-L1 inhibitors have shown promise, their limitations necessitate the development of alternative therapeutic strategies. This work addresses these challenges by developing a hexapeptide, KFM (Lys-Phe-Met-Phe-Met-Lys), capable of both directly downregulating PD-L1 and self-assembling into a ROS-responsive supramolecular hydrogel. This dual functionality allows Gel KFM to function as a localized drug delivery system and a PD-L1 inhibitor. Loading the hydrogel with mitoxantrone (MTX) and metformin (MET) further enhances the therapeutic effect by combining chemotherapy with PD-L1 downregulation. In vitro and in vivo studies demonstrate significant tumor growth inhibition, increased CD8+ T cell infiltration, and reduced intratumoral PD-L1 expression following peritumoral administration. Mechanistically, KFM promotes PD-L1 degradation via a ubiquitin-dependent pathway. This "carrier-free" delivery system expands the role of supramolecular hydrogels beyond passive carriers to active immunotherapeutic agents, offering a promising new strategy for cancer therapy.

Treatment of chronic osteomyelitis with gradient release of DGEA and vancomycin hydrogel-microsphere system and its mechanism.

In recent years, the treatment of chronic osteomyelitis mediated by biodegradable polymer platforms has received increasing attention. This paper reports an advanced drug delivery system, vancomycin (VA) and DGEA loaded microspheres embedded in injectable thermosensitive polypeptide hydrogels (i.e., hydrogel-microsphere (Gel-MP) construct), for continuous release of drugs with different mechanisms and more comprehensive treatment of chronic osteomyelitis. The Gel-MP construct exhibits continuous biodegradability and excellent biocompatibility. Microspheres (MP) are wrapped inside Gel. With the degradation of Gel, VA and MP are released from them, VA released with faster degradation speed, achieving a potent antibacterial effect and effectively controlling infection. Due to the slower degradation rate of MP compared to Gel, subsequently, DGEA is released from MP to induce bone formation and produce the effect of filling bone defects. Compared with other formulations, the in vivo combinational treatment of Gel/VA-MP/DGEA can simultaneously balance antibacterial and osteogenic effects. More importantly, local sustained-release drug delivery systems can significantly mitigate the systemic toxicity of drugs. Therefore, the injection local sequential drug delivery system has broad prospects in the clinical application of treating chronic osteomyelitis.

Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study.

Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20μmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1: poloxamer 407 and X2: carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798mPas), gelation temperature (36°C), gelation time (213s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

Effectiveness of a Local Drug Delivery System Based on Antimicrobial Peptides in Early Treatment of Peri-implantitis

ObjectiveTo analyse the effects of titanium implants coated with various antimicrobial peptide (AMP) layers on bacterial growth and early biofilm formation around the implants. MethodsA novel AMP mixture was constructed using Type I collagen, sulfonated succinimide 4- (N-Maleimidylphenyl) butyrate, and AMPs. Titanium discs treated with chitosan and hyaluronic acid solutions were reacted with the AMP mixture to obtain AMP-coated titanium discs. The drug release properties and inhibitory effects on the growth and early biofilm formation of Porphyromonasgingivalis (P. gingivalis) ATCC BAA-308 or Staphylococcus aureus (S. aureus) ATCC 25923 were analysed. ResultsThe antimicrobial activity of the 9-layer AMP-coated titanium discs against P. gingivalis ATCC BAA-308 and S.aureus ATCC 25923 was greatly higher relative to the 3-layer and 6-layer AMP-coated titanium discs (P < .05). The overall optical density and average optical density of titanium discs coated with 6 and 9 layers of AMPs were markedly inferior to those of uncoated titanium discs and discs coated with 3 layers of AMPs (P < .05). The drug release amounts from titanium discs coated with different layers of AMPs increased over time. ConclusionsThe prepared AMP-coated titanium discs effectively inhibit the growth of P. gingivalis and S. aureus, as well as early biofilm formation. The drug-laced discs demonstrate good durability and predictability in drug release, which may be beneficial for long-term therapeutic adoption.

Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice.

To effectively reduce the health impact of coronavirus disease (COVID-19), it is essential to adopt comprehensive strategies to protect individuals from severe acute respiratory syndrome. In that sense, much effort has been devoted to the discovery and repurposing of effective antiviral and anti-inflammatory molecules. The endogenous peptide angiotensin-(1-7) [Ang-(1-7)] has been recently proposed as a promising anti-inflammatory agent to control respiratory infections. Liposomes also emerged as a safe and effective drug carrier system for local drug delivery to the lungs. In this context, the aim of this study was to develop a liposomal formulation of Ang-(1-7) [LAng (1-7)] and investigate its impact on animal survival as well as its antiviral and anti-inflammatory efficacies after intranasal administration in transgenic K18-hACE2 mice infected with SARS-CoV-2. The liposomal formulation was prepared by the ethanol injection method, exhibiting a mean diameter of 100 nm and a polydispersity index of 0.1. Following treatment of infected mice every 12 hours for 5 days, LAng (1-7) extended animal survival compared to the control groups that received either empty liposomes, free Ang-(1-7), or phosphate-buffered saline. Furthermore, the treatment with LAng (1-7) significantly decreased the viral load, as well as IL-6 and tumor necrosis factor levels in the lungs. Conventional treatment with remdesivir by parenteral route used as a positive control promoted similar effects, leading to improved survival rates and reduced viral load in the lungs without significant effects on IL-6 level. In conclusion, liposomal Ang-(1-7) emerges as a promising formulation to improve the treatment and decrease the severity of respiratory infections, such as COVID-19.

A pH-Responsive Ti-Based Local Drug Delivery System for Osteosarcoma Therapy.

Osteosarcoma is one of the major bone cancers, especially for youngsters. The current treatment usually requires systemic chemotherapy and the removal of bone tumors. Titanium (Ti)-based implants can be modified as local drug delivery (LDD) systems for controllable and localized chemotherapeutic drug release. In this work, a pH-responsive Ti-based LDD prototype was designed by introducing polydopamine (PDA) to release doxorubicin (DOX) around osteosarcoma cells with low pH. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a contact angle meter were applied for surface characterization. Both direct and indirect cell culture modes were performed for biocompatibility and biofunction assessments. The results indicate that the Ti-based LDD prototype exhibits significant pH-dependent DOX release. The cumulative release can reach up to approximately 40% at pH = 6.0 after 72 h, but only around 20% at pH = 7.4. The Ti-based LDD implant shows good biocompatibility with approximately 93% viability of MC3T3 cells after direct culture in vitro for 24 h. Both direct and indirect culture modes verify the good anti-osteosarcoma function of the LDD implant, which should be attributed to the pH-responsive release of DOX.

IN VIVO APPLICATION OF LOCAL DRUG DELIVERY SYSTEMS AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL/TERATOID/RHABOID TUMOURS

Abstract AIMS Local drug delivery systems (LDDSs) applied during neurosurgery offer a means of overcoming poor blood brain barrier (BBB) permeability and have been extensively investigated for the treatment of adult gliomas, but to the best of our knowledge, not for the treatment of paediatric cerebellar tumours. Here we report the applicability of an LDDS against medulloblastoma group 3 (MB3) and atypical teratoid/rhaboid tumours (AT/RT), both of which are associated with poor prognoses. METHOD We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)- poly(ethyleneglycol) (PECE) hydrogel, which has been investigated with an array of therapeutic agents against numerous cancer types. Here, we loaded the PECE hydrogel with chemotherapeutics previously identified as being effective against primary MB3 and AT/RT in vitro, but which do not cross the BBB in vivo, namely CHIR99021, ribavirin and PG545. Biocompatibility and cytotoxicity of drug loaded hydrogels was assessed in vitro. LDDSs safety and efficacy was evaluated using patient derived MB3 and AT/RT intracranial xenograft surgical resection models. RESULTS The hydrogel was both biocompatible and effected cytotoxicity following drug release. In vivo efficacy experiments against MB3 indicated a comparable median survival in treatment arms receiving radiotherapy or CHIR99021 and PG545 loaded LDDS. However, combined radiotherapy and LDDS conferred a significant survival enhancement, including long-term survivors. Against AT/RT, the median survival of arms receiving radiotherapy was comparable to that of the CHIR99021 and ribavirin loaded LDDS, with long-term survivors observed only in the latter arm. CONCLUSION The application of LDDSs against cerebellar brain tumours offers a promising novel therapeutic alternative. For MB3, the combination of radiotherapy and a LDDS significantly enhances survival compared to radiotherapy alone. For AT/RT, the comparable survival of the LDDS and radiotherapy alone is encouraging and indicates the possibility of circumventing radiation-induced adverse effects for young children impacted by this disease.

Enzyme-responsive microgel with controlled drug release, lubrication and adhesion capability for osteoarthritis attenuation

The treatment of osteoarthritis (OA) remains challenging due to the narrow therapeutic window and rapid clearance of therapeutic agents, even with intra-articular administration, resulting in a low treatment index. Recent advancements in local drug delivery systems have yet to overcome the issues of uncontrolled burst release and short retention time, leading to suboptimal OA treatment outcome. Herein, we developed a methacrylate-crosslinking hyaluronic acid (HA) microgel (abbreviated as CXB-HA-CBP) that covalently conjugates the anti-inflammatory drug celecoxib (CXB) via a metalloproteinase-2 (MMP-2)-responsive peptide linker (GGPLGLAGGC) and a collagen II binding peptide (WYRGRLC). The GGPLGLAGGC linker is specifically cleaved by the overexpressed MMP-2 enzyme within the OA joint, enabling the sustained and on-demand release of CXB entity. The synergistic action of CXB and HA effectively inhibited macrophage activation and reduced the production of pro-inflammatory cytokines, protecting chondrocytes from damage. Furthermore, the collagen II peptide introduced on the microgel surface enabled a cartilage-binding function to form an artificial lubrication microgel layer on the cartilage surface to reduce cartilage wear. The CXB-HA-CBP microgel showed an extended retention time of up to 18 days in the affected joint, leading to an effective OA treatment in rats. This sophistically designed microgel, characterized by the prolonged retention time, sustained drug delivery, and enhanced lubrication, presents a promising biomedicine for OA treatment. Statement of significanceA new methacrylate-crosslinking hyaluronic acid (HA) microgel, covalently conjugated with the celecoxib (CXB)-GGPLGLAGGC and the collagen II binding peptide (CBP, peptide sequence: WYRGRLC), was developed. The overexpressed MMP-2 in OA joint cleaved the GGPLGLAGGC linker to trigger the CXB moiety release. Besides, the CBP on the surface of microgels enabled a cartilage-attaching ability, resulting in a prolonged retention time and an improved lubrication property in joint. This advanced drug-loading microgel remarkably reduced macrophage activation and pro-inflammation cytokine production, while protecting the chondrocytes via a dual action of CXB and HA. This study demonstrated that the enzyme-responsive drug-loading microgel could serve as an platform to efficiently attenuate osteoarthritis.

Thermosensitive multivesicular liposomal hydrogel: a potential platform for loco-regional drug delivery in the treatment of osteomyelitis caused by antibiotic-resistant biofilm-forming bacteria.

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies.

Sustained‐release delivery of antimicrobial drugs for the treatment of periodontal diseases: a narrative review

The inflammatory condition known as periodontitis can seriously impair a patient's quality of life and the oral cavity if left untreated. Although there isn't a reliable, standardized treatment for periodontitis, there have been numerous attempts, including tissue regeneration methods, antibiotics, and subgingival instrumentation. Given the limitations of the aforementioned treatment, local drug delivery systems appear to be the way of the future. These systems have the potential to release both tissue regeneration inducers and antibiotics gradually over time.

Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications.

Hydrogels, composed of hydrophilic polymer networks, have emerged as versatile materials in biomedical applications due to their high water content, biocompatibility, and tunable properties. They mimic natural tissue environments, enhancing cell viability and function. Hydrogels' tunable physical properties allow for tailored antibacterial biomaterial, wound dressings, cancer treatment, and tissue engineering scaffolds. Their ability to respond to physiological stimuli enables the controlled release of therapeutics, while their porous structure supports nutrient diffusion and waste removal, fostering tissue regeneration and repair. In wound healing, hydrogels provide a moist environment, promote cell migration, and deliver bioactive agents and antibiotics, enhancing the healing process. For cancer therapy, they offer localized drug delivery systems that target tumors, minimizing systemic toxicity and improving therapeutic efficacy. Ocular therapy benefits from hydrogels' capacity to form contact lenses and drug delivery systems that maintain prolonged contact with the eye surface, improving treatment outcomes for various eye diseases. In mucosal delivery, hydrogels facilitate the administration of therapeutics across mucosal barriers, ensuring sustained release and the improved bioavailability of drugs. Tissue regeneration sees hydrogels as scaffolds that mimic the extracellular matrix, supporting cell growth and differentiation for repairing damaged tissues. Similarly, in bone regeneration, hydrogels loaded with growth factors and stem cells promote osteogenesis and accelerate bone healing. This article highlights some of the recent advances in the use of hydrogels for various biomedical applications, driven by their ability to be engineered for specific therapeutic needs and their interactive properties with biological tissues.

Oral Patch/Film for Drug Delivery-Current Status and Future Prospects.

In recent years, there has been extensive research into drug delivery systems aimed at enhancing drug utilization while minimizing drug toxicities. Among these systems, oral patches/films have garnered significant attention due to their convenience, noninvasive administration, ability to bypass hepatic first-pass metabolism, thereby enhancing drug bioavailability, and their potential to ensure good compliance, particularly among special patient populations. In this review, from the perspective of the anatomical characteristics of the oral cavity and the advantages and difficulties of oral drug delivery, we illustrate the design ideas, manufacturing techniques, research methodologies, and the essential attributes of an ideal oral patch/film. Furthermore, the applications of oral patches/films in both localized and systemic drug delivery were discussed. Finally, we offer insights into the future prospects of the oral patch/film, aiming to provide valuable reference for the advancement of oral localized drug delivery systems.

Microneedle patch capable of dual drug release for drug delivery to brain tumors.

Primary brain tumors are mostly managed using surgical resection procedures. Nevertheless, in certain cases, a thin layer of tumors may remain outside of the resection process due to the possibility of permanent injury; these residual tumors expose patients to the risk of tumor recurrence. This study has introduced the use of microneedle patches implanted after surgery with a dual-release mechanism for the administration of doxorubicin. The proposed patches possess the capability to administer drugs directly to the residual tumors and initiate chemotherapy immediately following surgical procedures. Three-dimensional simulation of drug delivery to residual tumors in the brain has been performed based on a finite element method. The impact of four important parameters on drug delivery has been investigated, involving the fraction of drug released in the burst phase, the density of microneedles on the patch, the length of microneedles, and the microvascular density of the tumor. The simulation findings indicate that lowering the fraction of drug released in the initial burst phase reduces the maximum average concentration, but the sustained release that continues for a longer period, increasing the bioavailability of free drug. However, the area under curve (AUC) for different release rates remains unchanged due to the fact that an identical dose of drug is supplied in each instance. By increasing the density of microneedles on the patch, concentration accumulation is provided over an extensive region of tumor, which in turn induces more cancer cell death. A comparative analysis of various lengths reveals that longer microneedles facilitate profound penetration into the tumor layers and present better therapeutic response due to extensive area of the tumor which is exposure to chemotherapeutic drugs. Furthermore, high microvascular density, as a characteristic of the tumor microenvironment, is shown to have a significant impact on the blood microvessels drainage of drugs and consequently lower therapeutic response outcome. Our approach offers a computational framework for creating localized drug delivery systems and addressing the challenges related to residual brain tumors.

Antibacterial Activity of Cissus quadrangularis (Veldt Grape) Against Porphyromonas gingivalis, a Keystone Pathogen in Periodontal Disease: An In Vitro Study.

Porphyromonas gingivalis, a keystone pathogen and one of the primary pathogens responsible for periodontitis, leads to a chronic inflammatory condition that destroys the periodontal tissues and ultimately results in tooth loss. While conventional non-surgical therapy combined with antibiotics and local drug delivery systems are commonly used to treat periodontitis, certain medicinal herbs have also demonstrated efficacy in its prevention. Cissus quadrangularis L. (CQ), a perennial plant from the Vitaceae family, is widely recognized and used as a medicinal herb in many tropical countries, predominantly in India, Sri Lanka, Thailand, Java, West Africa, and the Philippines. The aim of the study was to determine the antibacterial activity of CQ against the periodontal keystone pathogen P. gingivalis. Aqueous and ethanolic extracts of CQ were prepared using a Soxhlet extractor. The antibacterial effectiveness of these extracts against the periodontal pathogen P. gingivalis was evaluated at different concentrations, and the minimal inhibitory concentration (MIC) was determined using broth microdilution. The ethanolic extract of CQ mixed with 10% dimethyl sulfoxide (DMSO) showed higher inhibition compared to the aqueous extract of CQ against P. gingivalis. Our study revealed the potent inhibitory effects of CQ against P. gingivalis. Both aqueous and ethanolic extracts displayed MIC values of 500 µg/mL. Notably, the ethanolic extract of CQ, dissolved in 10% DMSO, demonstrated superior efficacy with a lower IC50 value of 194.36 µg/mL. These findings indicate promising potential for CQ in the management of periodontal disease.

Local delivery of carboplatin-loaded hydrogel and calcium carbonate enables two-stage drug release for limited-dose radiation to eliminate mouse malignant glioma

Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy.We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model.The doses of carboplatin in CPH and CPCC treatments were 150 μL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 μg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation.Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.