Local Drug Delivery System Research Articles

Formulation of In-situ Thermoreversible Gel with Moringa oleifera Lam Extract as a Local Drug Delivery System for Adjunct Periodontal Treatment

Introduction: Periodontal disease is an outcome of a plethora of molecular mechanisms associated with oxidative stress, inflammation and oral microorganisms is managed by surgical or non surgical therapies with systemic antibiotics. However, local drug delivery system is known to augment the currently available therapies and improves prognosis. Although, there are several local drug delivery systems available, the search for an ideal agent with antioxidant, antimicrobial and anti-inflammatory properties continues. Moringa oleifera Lam extracts is one such wonder plant with all the above mentioned effects. Aim: To formulate an in-situ thermoreversible gel with Moringa oleifera Lam extract that could be used as a local drug delivery system as an adjunct to periodontal treatment. Materials and Methods: This in-vitro study was conducted in Nanotechnology Laboratory, Department of Pharmacology at Saveetha Dental College, from May 2022 to June 2022. For preparation of thermoreversible gel the 19% of thermogelling polymer poloxamer 407 (15% to 30%w/v) which the least concentration that demonstrates thermoreverisibility at 36°C and 0.2% which is the least concentration of mucoadhesive polymer carbapol 934 (0.2% to 0.5% w/v) which forms sol-gel transition and 5% aqueous extract of Moringa oleifera and cold deionised water were used. Surface pH, gelation temperature, syringeability, in-vitro drug release, stability, gelation time and Fourier Transform Infrared Spectroscopy (FTIR) analysis was done Results: The surface pH of the gel was 6.94±0.091 with a gelation temperature of 34°C±0.5. The gel was flowable with good stability and fast release of eight hours. The chemical components compatability study of Moringa oleifera Lam powder, thermoreversible gel without extract and thermoreversible gel with extract were subjected to FITR analysis. The spectral analysis showed no significant chemical interaction between the Moringa oleifera and thermoreversible gel. Conclusion: The study concluded that the thermoreversible gel with Moringa oleifera Lam extracts could be used as an adjunct for the management of periodontal disease with good bioavailability. However, future clinical studies have to be conducted to validate the results of the present study.

Continuous local antibiotic perfusion: A treatment strategy that allows implant retention in fracture-related infections

Fracture-related infections are difficult to treat because of the formation of biofilms around implants. Systemic antibiotics are notoriously ineffective against biofilms due to their insufficient penetration of tissues with poor vascularity. The goal of treating fracture-related infections is to achieve bone union while retaining the implant. Our proposal of continuous local antibiotic perfusion is a sustained local delivery system of sufficient antibiotics to bone and soft tissue infection sites, including to bone marrow via needles as intra-medullary antibiotics perfusion and to soft-tissue via double-lumen subcutaneous tubes as intra-soft tissue perfusion. In this study, we examined the outcomes of 40 patients treated for fracture-related infections using continuous local antibiotic perfusion between 2015 and 2021 at Steel Memorial Hirohata Hospital, Himeji, Japan. The antibiotic used for continuous local antibiotic perfusion was gentamicin in all cases. Implant removal was required in five patients. Two patients required toe amputation and knee arthrodesis, while the remaining 38 patients achieved fracture union. Only one case of transient acute renal injury as a systemic side effect was observed, but it soon resolved. The blood concentration of gentamicin could be adjusted to less than the trough level. Continuous local antibiotic perfusion is a novel local drug delivery system that has the potential of delivering sufficient concentrations of antibiotics with few systemic side effects; it is a useful option for the treatment of fracture-related infections.

Drug delivery systems for oral disease applications.

There are many restrictions on topical medications for the oral cavity. Various factors affect the topical application of drugs in the oral cavity, an open and complex environment. The complex physical and chemical environment of the oral cavity, such as saliva and food, will influence the effect of free drugs. Therefore, drug delivery systems have served as supporting structures or as carriers loading active ingredients, such as antimicrobial agents and growth factors (GFs), to promote antibacterial properties, tissue regeneration, and engineering for drug diffusion. These drug delivery systems are considered in the prevention and treatment of dental caries, periodontal disease, periapical disease, the delivery of anesthetic drugs, etc. These carrier materials are designed in different ways for clinical application, including nanoparticles, hydrogels, nanofibers, films, and scaffolds. This review aimed to summarize the advantages and disadvantages of different carrier materials. We discuss synthesis methods and their application scope to provide new perspectives for the development and preparation of more favorable and effective local oral drug delivery systems.

Sustained delivery of gemcitabine via in situ injectable mussel-inspired hydrogels for the local therapy of pancreatic cancer.

The issue of pervasively enhanced drug resistance of pancreatic cancer is fundamental to a better understanding of gemcitabine-based chemotherapy. Currently available treatment plans involving injectable therapeutics are mainly engineered to improve the performance and broaden their applications in the domain of biomedicine. Fixed-dose-rate infusion of free gemcitabine (Gem) has drawn appropriate attention for its potent anti-tumor efficacy against various solid tumors, whereas it remains a considerable challenge to extend its application and achieve better treatment. Here, we have prepared and demonstrated a long-acting delivery system using gemcitabine and injectable in situ hydrogel for the localized treatment of pancreatic cancer. The hydrogel was prepared using polysaccharide derivatives, oxidized-carboxymethylcellulose (OCMC) and carboxymethylchitosan (CMCS) at optimal ratios by a dopamine-functionalized method for the controlled release of Gem. In vitro drug release behaviors for up to a week indicated sustained drug release of the Gem delivery system. Moreover, desirable apoptosis promotion and apparent cellular proliferation inhibition associated with the drug depot have been found in vitro against BxPC-3 pancreatic cancer cells, bringing minimized side effects to systemic normal tissues. The current findings manifested that the release out of the localized delivery platform in a sustained pattern afforded a durable gemcitabine-based chemotherapy effect and inhibited tumor metastasis more persistently after intratumoral injection of the Gem@Gel system, thereby advancing the development of novel drug-loaded materials with properties not accessed previously.

Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics.

Titanium implants have always been regarded as one of the gold standard treatments for orthopedic applications, but they still face challenges such as pain, bacterial infections, insufficient osseointegration, immune rejection, and difficulty in personalizing treatment in the clinic. These challenges may lead to the patients having to undergo a painful second operation, along with increased economic burden, but the use of drugs is actively solving these problems. The use of systemic drug delivery systems through oral, intravenous, and intramuscular injection of various drugs with different pharmacological properties has effectively reduced the levels of inflammation, lowered the risk of endophytic bacterial infection, and regulated the progress of bone tumor cells, processing and regulating the balance of bone metabolism around the titanium implants. However, due to the limitations of systemic drug delivery systems—such as pharmacokinetics, and the characteristics of bone tissue in the event of different forms of trauma or disease—sometimes the expected effect cannot be achieved. Meanwhile, titanium implants loaded with drugs for local administration have gradually attracted the attention of many researchers. This article reviews the latest developments in local drug delivery systems in recent years, detailing how various types of drugs cooperate with titanium implants to enhance antibacterial, antitumor, and osseointegration effects. Additionally, we summarize the improved technology of titanium implants for drug loading and the control of drug release, along with molecular mechanisms of bone regeneration and vascularization. Finally, we lay out some future prospects in this field.

Formulation Development and Evaluation of Itraconazole Loaded Invasomes Hydrogel

Topical drug administration is a localized drug delivery system anywhere in the body through ophthalmic, rectal, vaginal and skin as topical routes. Skin is one of the most readily accessible organs on human body for topical administration and is main route of topical drug delivery system. There are various skin infections caused by fungus. An antifungal medication is a pharmaceutical fungicide used to treat mycoses such as athlete’s foot ringworm, candidiasis. Antifungal works by exploiting differences between mammalian and fungal cells to kill the fungal organism without dangerous effect on host. Itraconazole (ITZ) is commonly used in the treatment of fungal infections. It has low bioavailability (55%) because of low aqueous solubility and first pass effect. Hence we attempted to develop Itraconazole-loaded invasomes hydrogel. ITZ-loaded invasomes were prepared by conventional thin layer evaporation technique using Phospholipon 90H, terpene (Limonene) and ethanol. The optimized ITZ-loaded invasomes was incorporated into carbopol 934p (0.5 to 2%) solution to get a hydrogel for improving convenience in superficial application. FT-IR studies revealed no interaction between the drug and excipients. The formulated hydrogel formulation was evaluated with parameter pH, viscosity, gel strength, drug content, spread ability, in-vitro release test, wash ability, extrudability study and stability studies. The formulation OIGF4 showed a drug content of 99.12% and drug release of 99.78% in 72 hrs, which contains carbopol 934p concentration 2%w/w. The present work also focuses on making the formulation more pharmaceutically acceptable.

Antioxidant Enzymes Sequestered within Lipid-Polymer Hybrid Nanoparticles for the Local Treatment of Inflammatory Bowel Disease.

The local treatment of inflammatory bowel disease (IBD) by enzyme therapeutics is challenging owing to hostile environments in the gastrointestinal tract, leading to the hydrolysis and enzymatic degradation of labile proteins. In this study, safe and efficient local drug delivery systems were developed by antioxidant superoxide dismutase (SOD) sequestered within lipid-polymer hybrid nanoparticles through sequential self-assembly processes. Interestingly, we found that the sequestered SOD exhibited long-term enzymatic stability and comparable biological activity to the enzymes in the native form, probably owing to particle encapsulation providing a physical barrier to prevent the enzymolysis of proteins. We demonstrated that nanoparticle-based local drug delivery systems showed excellent mucus-penetrating ability and inflammation-targeting properties, owing to the particle surface with a poly(ethylene glycol) (PEG) coating and folate functionalization, thus improving mucosal retention time and drug delivery efficiency within the colorectal region. Furthermore, SOD-containing lipid-polymer hybrid nanoparticles could effectively mitigate inflammatory responses by regulating the secretion of inflammation-associated cytokines, thus increasing therapeutic outcomes in colitis mice through intrarectal administration. The findings indicated that antioxidant enzymes sequestered within lipid-polymer hybrid nanoparticles might be potential enzyme therapeutics for the local treatment of some inflammatory diseases in the near future.

Mucoadhesive silver nanoparticle-based local drug delivery system for peri-implantitis management in COVID-19 era. Part 1: antimicrobial and safety in-vitro analysis

BackgroundPseudomonas aeruginosa, a major respiratory pathogen, has been isolated from peri-implant sites and is associated with dental implant failure. This in-vitro study (part 1) aimed to fabricate a novel mucoadhesive silver nanoparticle-based local drug delivery chip, evaluate its antimicrobial efficacy against P. aeruginosa, and its safety for the treatment of peri-implantitis. Materials and methodsSilver nanoparticles were synthesized and characterized using a transmission electron microscope (TEM). The local drug delivery chip was fabricated using gelatin, glycerol, silver nanoparticle solution (2.5 μg/ml, 5 μg/ml, 7.5 μg/ml, and 10 μg/ml), glutaraldehyde, and sodium alginate solution. These chips were evaluated for physical parameters, effect on viability of murine macrophage cell line J774A.1, and antimicrobial activity (using Kirby-Bauer disc diffusion method with 18 h incubation period) against P. aeruginosa ATCC 27853. ResultsSilver nanoparticle antimicrobial chip exhibited dimensions of 4 mm × 5 mm x 0.4 mm, 5.8 mg weight, pH 5–6, folding endurance 1.04, and one-year stability. P. aeruginosa was susceptible to ≥ 7.5 μg/ml concentration of silver nanoparticles (spherical shape with particle size ranging from 10 to 100 nm). Murine macrophage cells exhibited 93% viability after 24 h incubation with silver nanoparticle chips. ConclusionThe novel silver nanoparticle chip showed dimensional stability, minimal effect on murine macrophage cell viability, and significant antimicrobial activity against P. aeruginosa. With the further establishment of its effective dosage and safety, this chip could be used as an adjunct to mechanical debridement (as a non-aerosol generating procedure) in treating peri-implantitis, especially during the ongoing coronavirus disease 2019 (COVID-19) pandemic.

Local drug delivery system for the treatment of tongue squamous cell carcinoma in rats.

The present study describes a local drug delivery system with two functions, which can suppress tumor growth and accelerate wound healing. Thе system consists of a two-layer multicomponent fibrin-based gel (MCPFTG). The internal layer of MCPFTG, which is in direct contact with the wound surface, contains cisplatin placed on a CultiSpher-S collagen microcarrier. The external layer of MCPFTG consists of a CultiSpher-S microcarrier with lyophilized bone marrow stem cells (BMSCs). The efficacy of MCPFTG was evaluated in a rat model of squamous cell carcinoma of the tongue created with 4-nitroquinoline 1-oxide. The results of the study showed that, within 20–25 days, a non-healing wound of the tongue was formed in animals that underwent only 85% resection of squamous cell carcinoma, while rapid progression of the residual tumor was concomitantly observed. Immunohistochemical methods revealed high expression of cyclin D1 and low expression of E-cadherin in these animals. Additionally, high expression of p63 and Ki-67 was noted. In 80% of animals with squamous cell carcinoma of the tongue that were treated with MCPFTG after 85% tumor resection, a noticeable suppression of tumor growth was evident throughout 150 days, and tumor recurrence was not detected. Immunohistochemistry revealed low or moderate expression of cyclin D1, and high expression of E-cadherin throughout the whole observation period. The MCPFTG-based local drug delivery system was shown to be effective in suppressing tumor growth and preventing recurrence. MCPFTG decreased the toxicity of cisplatin and enhanced its antitumor activity. In addition, lyophilized paracrine BMSC factors present in MCPFTG accelerated wound healing after tumor removal. Thus, the present study suggests novel opportunities for the development of a multifunctional drug delivery system for the treatment of squamous cell carcinoma.

MOF Hydrogel With Structurally Dynamic Properties as Stimuli-Responsive Localized Drug Delivery System for Cancer Therapy

Metal-organic framework (MOF) is an exciting class of porous biomaterial that have been considered as carrier to store and deliver therapeutic drugs. However, pure MOF similar with other nanomaterial is still limitedly used in clinic because of premature diffusion of their payloads and tissue off-targeting behavior. To figure out above challenges, we design a MOF hydrogel with structurally dynamic properties, i.e. self-healing and shear-thinning, as injectable localized drug delivery platform. To realize the presented drug encapsulating hydrogel, the doxorubicin loaded MOF (MOF@DOX) suspension is mixed with home-made bisphosphonate modified hyaluronic acid (HA-BP) polymeric binder. The dynamic coordination bonds basing hydrogel cross-linkage between the bisphosphonate groups on HA-BP macromolecule and the zinc ion on MOF particle affords the hydrogel of injectable, shear-thinning, self-healing properties. HA-BP•MOF@DOX hydrogel demonstrates pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The animal experiments reveal HA-BP•MOF@DOX hydrogel of enhanced capability in terms of suppression tumor growth comparing with MOF@DOX group, which can be caused by the drug localization in hydrogel superstructure and sustainable release at tumor site. Therefore, the presented injectable dynamic MOF hydrogel is a promising in vivo localized drug delivery system for cancer treatment.

Fast dissolving nanofiber mat for the local antimicrobial application of roxithromycin in oral cavity

Fast disintegrating and dissolving nanofiber (NF) mat was devised to deliver roxithromycin for the treatment of the respiratory tract infection. NF membrane was made by an electrospinning process with poly(vinyl alcohol) (PVA), hydroxypropyl-β-cyclodextrin (HP-β-CD), and d-α-tocopheryl polyethylene glycol succinate (TPGS) for local application of roxithromycin. Roxithromycin has a poor water solubility thus HP-β-CD is introduced for enhancing drug solubility by forming an inclusion complex in this study. The addition of TPGS provided multiple roles such as accelerating wetting, disintegration, and dissolution speed and overcoming bacterial resistance. Roxithromycin was successfully entrapped in NF structure and drug amorphization occurred during the electrospinning process. PVA/HP-β-CD/TPGS/roxithromycin (PHTR) NF exhibited faster wetting, disintegration, and dissolution speed rather than the other NF mats. PHTR NF displayed higher antibacterial potentials in Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) compared to other NF mat formulations. The administration of PHTR NF to oral cavity in pneumococcal disease mouse model provided the most efficient therapeutic potentials in lung tissue. Designed multiple phase-based NF mat may be one of powerful local drug delivery systems for the therapy of respiratory tract infection.

Polycaprolactone nanofibers as an adjuvant strategy for Tamoxifen release and their cytotoxicity on breast cancer cells.

Breast cancer is the second leading cause of death in women, and tamoxifen citrate (TMX) is accepted widely for the treatment of hormone receptor–positive breast cancers. Several local drug-delivery systems, including nanofibers, have been developed for antitumor treatment. Nanofibers are biomaterials that mimic the natural extracellular matrix, and they have been used as controlled release devices because they enable highly efficient drug loading. The purpose of the present study was to develop polycaprolactone (PCL) nanofibers incorporating TMX for use in the treatment of breast tumors. Pristine PCL and PCL-TMX nanofibers were produced by electrospinning and characterized physiochemically using different techniques. In addition, an in vitro study of TMX release from the nanofibers was performed. The PCL-TMX nanofibers showed sustained TMX release up to 14 h, releasing 100% of the TMX. The Resazurin reduction assay was used to evaluate the TMX cytotoxicity on MCF-7 breast cancer cell line and PBMCs human. The PCL-TMX nanofiber was cytotoxic toPBMCs and MCF-7. Based on these results, the PCL-TMX nanofibers developed have potential as an alternative for local chronic TMX use for breast cancer treatment, however tissue tests must be done.

Systemic and Local Silk-Based Drug Delivery Systems for Cancer Therapy.

Simple SummaryApplication of drug delivery systems (DDS) in oncology may increase the effectiveness of cancer treatment and reduce the associated adverse side effects. Although various biomaterials can be considered for the development of DDS, the materials of natural origin offer great biocompatibility and degradability. Silk is a natural biomaterial with exceptional properties, and one of them is the possibility to form diverse morphological structures. Scaffolds, films, hydrogels, fibers, foams spheres, capsules, microneedles, among others, can be used for local and systemic drug delivery. In this review, we described the various silk-based DDS for potential application in oncology. However, the unique silk properties combined with the possibility of their further modifications and blending open the gate to numerous potential biomedical applications, not only in the oncology field.For years, surgery, radiotherapy, and chemotherapy have been the gold standards to treat cancer, although continuing research has sought a more effective approach. While advances can be seen in the development of anticancer drugs, the tools that can improve their delivery remain a challenge. As anticancer drugs can affect the entire body, the control of their distribution is desirable to prevent systemic toxicity. The application of a suitable drug delivery platform may resolve this problem. Among other materials, silks offer many advantageous properties, including biodegradability, biocompatibility, and the possibility of obtaining a variety of morphological structures. These characteristics allow the exploration of silk for biomedical applications and as a platform for drug delivery. We have reviewed silk structures that can be used for local and systemic drug delivery for use in cancer therapy. After a short description of the most studied silks, we discuss the advantages of using silk for drug delivery. The tables summarize the descriptions of silk structures for the local and systemic transport of anticancer drugs. The most popular techniques for silk particle preparation are presented. Further prospects for using silk as a drug carrier are considered. The application of various silk biomaterials can improve cancer treatment by the controllable delivery of chemotherapeutics, immunotherapeutics, photosensitizers, hormones, nucleotherapeutics, targeted therapeutics (e.g., kinase inhibitors), and inorganic nanoparticles, among others.

A state-of-the-art review of the fabrication and characteristics of titanium and its alloys for biomedical applications.

Commercially pure titanium and titanium alloys have been among the most commonly used materials for biomedical applications since the 1950s. Due to the excellent mechanical tribological properties, corrosion resistance, biocompatibility, and antibacterial properties of titanium, it is getting much attention as a biomaterial for implants. Furthermore, titanium promotes osseointegration without any additional adhesives by physically bonding with the living bone at the implant site. These properties are crucial for producing high-strength metallic alloys for biomedical applications. Titanium alloys are manufactured into the three types of α, β, and α + β. The scientific and clinical understanding of titanium and its potential applications, especially in the biomedical field, are still in the early stages. This review aims to establish a credible platform for the current and future roles of titanium in biomedicine. We first explore the developmental history of titanium. Then, we review the recent advancement of the utility of titanium in diverse biomedical areas, its functional properties, mechanisms of biocompatibility, host tissue responses, and various relevant antimicrobial strategies. Future research will be directed toward advanced manufacturing technologies, such as powder-based additive manufacturing, electron beam melting and laser melting deposition, as well as analyzing the effects of alloying elements on the biocompatibility, corrosion resistance, and mechanical properties of titanium. Moreover, the role of titania nanotubes in regenerative medicine and nanomedicine applications, such as localized drug delivery system, immunomodulatory agents, antibacterial agents, and hemocompatibility, is investigated, and the paper concludes with the future outlook of titanium alloys as biomaterials.Graphic abstract

Biopolymer Hydrogel Scaffolds Containing Doxorubicin as A Localized Drug Delivery System for Inhibiting Lung Cancer Cell Proliferation.

A hydrogel scaffold is a localized drug delivery system that can maintain the therapeutic level of drug concentration at the tumor site. In this study, the biopolymer hydrogel scaffold encapsulating doxorubicin was fabricated from gelatin, sodium carboxymethyl cellulose, and gelatin/sodium carboxymethyl cellulose mixture using a lyophilization technique. The effects of a crosslinker on scaffold morphology and pore size were determined using scanning electron microscopy. The encapsulation efficiency and the release profile of doxorubicin from the hydrogel scaffolds were determined using UV-Vis spectrophotometry. The anti-proliferative effect of the scaffolds against the lung cancer cell line was investigated using an MTT assay. The results showed that scaffolds made from different types of natural polymer had different pore configurations and pore sizes. All scaffolds had high encapsulation efficiency and drug-controlled release profiles. The viability and proliferation of A549 cells, treated with gelatin, gelatin/SCMC, and SCMC scaffolds containing doxorubicin significantly decreased compared with control. These hydrogel scaffolds might provide a promising approach for developing a superior localized drug delivery system to kill lung cancer cells.

Controlled temperature-mediated curcumin release from magneto-thermal nanocarriers to kill bone tumors

Systemic chemotherapy has lost its position to treat cancer over the past years mainly due to drug resistance, side effects, and limited survival ratio. Among a plethora of local drug delivery systems to solve this issue, the combinatorial strategy of chemo-hyperthermia has recently received attention. Herein we developed a magneto-thermal nanocarrier consisted of superparamagnetic iron oxide nanoparticles (SPIONs) coated by a blend formulation of a three-block copolymer Pluronic F127 and F68 on the oleic acid (OA) in which Curcumin as a natural and chemical anti-cancer agent was loaded. The subsequent nanocarrier SPION@OA-F127/F68-Cur was designed with a controlled gelation temperature of the shell, which could consequently control the release of curcumin. The release was systematically studied as a function of temperature and pH, via response surface methodology (RSM). The bone tumor killing efficacy of the released curcumin from the carrier in combination with the hyperthermia was studied on MG-63 osteosarcoma cells through Alamar blue assay, live-dead staining and apoptosis caspase 3/7 activation kit. It was found that the shrinkage of the F127/F68 layer stimulated by elevated temperature in an alternative magnetic field caused the curcumin release. Although the maximum release concentration and cell death took place at 45 °C, treatment at 41 °C was chosen as the optimum condition due to considerable cell apoptosis and lower side effects of mild hyperthermia. The cell metabolic activity results confirmed the synergistic effects of curcumin and hyperthermia in killing MG-63 osteosarcoma cells.

Advances in Drug Delivery and Theranostics

Advances in Drug Delivery and Theranostics

Should local drug delivery systems be used in dentistry?

In dentistry, the use of biomaterial-based drug delivery systems (DDS) aiming the release of the active compounds directly to the site of action is slowly getting more awareness among the scientific and medical community. Emerging technologies including nanotechnological platforms are offering novel approaches, but the majority are still in the proof-of-concept stage. This study critically reviews the potential use of DDS in anesthesiology, oral diseases, cariology, restorative dentistry, periodontics, endodontics, implantology, fixed and removable prosthodontics, and orthodontics with a special focus on infections. It also stresses the gaps and challenges faced. Despite numerous clinical and pharmacological advantages, some disadvantages of DDS pose an obstacle to their widespread use. The biomaterial's biofunctionality may be affected when the drug is incorporated and may cause an additional risk of toxicity. Also, the release of sub-therapeutic levels of drugs such as antibiotics may lead to microbial resistance. Multiple available techniques for the manufacture of DDS may affect drug release profiles and their bioavailability. If the benefits outweigh the costs, DDS may be potentially used to prevent or treat oral pathologies as an alternative to conventional strategies. A case-by-case approach must be followed.

Local Drug Delivery Systems for Vital Pulp Therapy: A New Hope.

Vital pulp therapy (VPT) is deliberated as an ultraconservative/minimally invasive approach for the conservation of vital pulpal tissues, preservation of dental structure, and maintenance of tooth function in the oral cavity. In VPT, following the exposure of the dental pulp, the environment is prepared for the possible healing and probable refunctionalisation of pulpal connective tissue. However, to succeed in VPT, specific biomaterials are used to cover and/or dress the exposed pulp, lower the inflammation, heal the dental pulp, provoke the remaining odontoblastic cells, and induce the formation of a hard tissue, i.e., the dentinal bridge. It can be assumed that if the employed biomaterial is transferred to the target site using a specially designed micro-/nanosized local drug delivery system (LDDS), the biomaterial would be placed in closer proximity to the connective tissue, may be released in a controlled and sustained pattern, could properly conserve the remaining dental pulp and might appropriately enhance hard-tissue formation. Furthermore, the loaded LDDS could help VPT modalities to be more ultraconservative and may minimise the manipulation of the tooth structure as well as pulpal tissue, which could, in turn, result in better VPT outcomes.

Intra-medullary antibiotics perfusion (iMAP) for the control of fracture-related infection early after osteosynthesis.

In our hospital, cases of bone and soft tissue infections have been treated with continuous local antibiotics perfusion that allows for continuous circulation of antibiotics throughout the infected lesion. We termed this treatment "intramedullary antibiotics perfusion (iMAP)" for bone infection such as fracture-related infection (FRI) and "intrasoft tissue antibiotics perfusion" for soft tissue infection. Many cases are treated with both modalities. To introduce iMAP, this study focused on the patients with FRI treated with iMAP and reviewed their treatment outcomes. We included 10 patients with FRI treated with iMAP between 2004 and 2017. The iMAP needles were inserted near the infected lesion, and an aminoglycoside antimicrobial was continuously administered. Patient characteristics, pathogenic bacteria, administered antibiotics, duration of administration, concentrations of antibiotics in blood and leachate fluid, fracture union rate, implant retention rate, and complications were studied. The mean age of patients was 59.9years, and the mean follow-up period was 2.5years. Affected bones were the tibia (n = 8), humerus (n = 1), and fibula (n = 1). Deep infections developed on average 29.9days after osteosynthesis. Pathogenic bacteria were methicillin-susceptible Staphylococcus aureus (n = 6), methicillin-resistant S. aureus (n = 2), and unknown (n = 2). Average iMAP duration was 17.1days. In all patients, infection was eradicated while preserving the implants, and fracture union was achieved without complications. iMAP is a novel local drug delivery system allowing high concentrations of antibiotics to be administered without complications and is useful in the treatment of FRI.