Local Drug Delivery System Research Articles

Development of a local drug delivery system for promoting the regeneration of infective bone defects: composite films with controlled properties

Development of a local drug delivery system for promoting the regeneration of infective bone defects: composite films with controlled properties

Polymeric nanofiber leveraged co-delivery of anti-stromal PAK1 inhibitor and paclitaxel enhances therapeutic effects in stroma-rich 3D spheroid models

The role of tumor stroma in solid tumors has been widely recognized in cancer progression, metastasis and chemoresistance. Cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and promoting cancer cell stemness and resistance via reciprocal crosstalk. Residual tumor tissue after surgical removal as well as unresectable tumors face therapeutic challenges to achieve curable outcome. In this study, we propose to develop a dual delivery approach by combining p21-activated kinase 1 (PAK1) inhibitor (FRAX597) to inhibit tumor stroma and chemotherapeutic agent paclitaxel (PTX) to kill cancer cells using electrospun nanofibers. First, the role of the PAK1 pathway was established in CAF differentiation, migration and contraction using relevant in vitro models. Second, polycaprolactone polymer-based nanofibers were fabricated using a uniaxial electrospinning technique to incorporate FRAX597 and/or PTX, which showed a uniform texture and a prolonged release of both drugs for 16 days. To test nanofibers, stroma-rich 3D heterospheroid models were set up which showed high resistance to PTX nanofibers compared to stroma-free homospheroids. Interestingly, nanofibers containing PTX and FRAX597 showed strong anti-tumor effects on heterospheroids by reducing the growth and viability by > 90 % compared to either of single drug-loaded nanofibers. These effects were reflected by reduced intra-spheroidal expression levels of collagen 1 and α-smooth muscle actin (α-SMA). Overall, this study provides a new therapeutic strategy to inhibit the tumor stroma using PAK1 inhibitor and thereby enhance the efficacy of chemotherapy using nanofibers as a local delivery system for unresectable or residual tumor. Use of 3D models to evaluate nanofibers highlights these models as advanced in vitro tools to study the effect of controlled release local drug delivery systems before animal studies.

Exploring Synergies of Lotus Seed Extract-Hyaluronic Acid Gel for Enhanced Local Drug Delivery

OBJECTIVE The plant species Nelumbo nucifera (lotus) is widely used in traditional medicine and is known to contain flavonoids, alkaloids, and other polyphenols which contribute to its potent antioxidant, anti-inflammatory properties in addition to its being a remedy for cardiac diseases. Hyaluronic acid, present in skin and connective tissue, is well known for its tissue regeneration and wound healing properties. The present study aimed to determine the antioxidant and anti-inflammatory effect of the hyaluronic acid gel combined with lotus seed extract and how this combination could be used as an effective local drug delivery system for the treatment of periodontitis. METHODS A 2% solution of hyaluronic acid gel was combined with increasing concentrations of prepared lotus seed extract. A DPPH test was conducted to determine the antioxidant activity of the resultant mixture at increasing concentrations. Additionally, anti-inflammatory activity was assessed using a UV spectrometer, and the spreadability of the gel was measured using the sliding glass slide method. The values obtained were plotted on graphs.. RESULTS The DPPH scavenging assay revealed that lotus seed extract with 2% hyaluronic acid gel exhibited increased antioxidant activity in a dose-dependent manner with IC50 at 76 μL. The lotus seed extract with 2% hyaluronic acid gel also showed increased anti-inflammatory properties in a dose-dependent manner with IC50 at 271 μL. Moreover, the spreadability of the lotus seed extract with 2% hyaluronic acid gel was found to be 42 mm. CONCLUSIONS Lotus seed extract shows potent antioxidant and anti- inflammatory activities which vary with the concentration of the extract, and can serve as an effective local drug delivery system.

Deep eutectic solvent based self-healable, stretchable and injectable eutectogels: A versatile platform for breast cancer treatment

Recent focus is on developing cancer treatments that overcome challenges of high-dose chemotherapy, providing improved safety, effectiveness, and site-specific targeting through responsive mechanisms. In our quest for an advanced drug delivery vehicle, herein we have developed a self-healable and injectable polymeric eutectogels that responds to intracellular biological stimuli i.e., pH and temperature. The eutectogels made through interacting imidazolium based deep eutectic solvents with polyvinyl alcohol serve as a local drug delivery system for cancer therapeutics, releasing the anti-cancer drug 5-fluorouracil (5-FU) to the targeted site through intracellular pH, i.e. pH 5.0. Rheology experiments showed strong mechanical strength (>7.3 % strain) for the studied eutectogels that have hierarchical and porous 3D network morphology formed by thick fibers. It exhibits crucial qualities- swelling, injectability, and self-healing- essential for an effective drug delivery vehicle. Additionally, eutectogels demonstrates outstanding biocompatibility, with hemolysis below 2 %, ensuring blood compatibility and sustained viability in HaCaT cells. Leveraging these properties, 5-FU-loaded eutectogels were studied for in vitro cytotoxicity (MCF-7 and HeLa) and drug release that revealed that the eutectogels can be used for targeted delivery under physiological conditions and can more efficiently kill cancerous cells.

Drug delivery with melt-spun liquid-core fibers

Conventional local drug delivery systems often encounter issues such as burst-release, limited drug reservoirs, rigidity, and low mechanical performance. We present an innovative approach to local drug delivery utilizing melt-spun drug-loaded liquid-core filaments (LiCoFs). LiCoFs were produced, incorporating fluorescein sodium salt as the model drug, dissolved in various liquid core materials, and enveloped by poly(ε-caprolactone) as the sheath material. We assessed thermal, mechanical, and structural properties of LiCoFs and have conducted extensive drug diffusion trials. Some trials involved pre-exchange of the liquid core with ibuprofen, bovine serum albumin–fluorescein isothiocyanate and methylene blue solutions using a pumping device. It was observed that diffusion mechanisms and diffusion rates depend on temperature, core size/sheath thickness, sheath permeability, carrier liquid type, drug molecule properties, and the drug's affinity to the sheath polymer. These drug-loaded LiCoFs pave the way towards a new generation of medical textiles facilitating controlled, local drug delivery.

Effect of microbubble as local drug delivery system in endodontic management - An In-Vitro study

Background and ObjectivesMicrobubbles (MBs) are gas or vapor-filled cavities inside liquids with sizes ranging from 2 to 3 µm. Recently, MBs have shown great promise in nanomedicine owing to their high encapsulation efficiency, targeted drug release, improved biocompatibility, and longer blood circulation. Furthermore, they are more suitable for focusing on particular body regions and are safer and non-invasive. MBs generators are used to create bubbles in fluid dynamics, chemistry, medicine, agriculture, and the environment. Drug delivery using MBs increases penetration without causing systemic toxicity.In this study, we examined whether the use of microbubbles as a local drug-delivery mechanism increases tubular penetration of endodontic medications and irrigant. Materials and MethodsAn Enterococcus faecalis culture was added to 38 dentin cylinders of single-rooted teeth. Samples were divided into the experimental and control groups that received a triple antibiotic paste with and without MB infusion (n = 19 in each group), respectively. After 14 days, the number of live bacteria in the samples was determined using confocal laser scanning microscopy. ResultsAfter 14 days of contact with the medication, the percentages of live and dead bacteria were assessed. Results show that Group 2 (Triple antibiotic infused micro bubble) showed significantly (P < 0.05) higher antibacterial efficacy than Group 1 (TAP). ConclusionIn this study, the antibacterial efficacy was significantly higher in the experimental group than in the control group. Therefore, within the limitations of the study it can be said that MB infusion is a viable technique to improve root canal disinfection. Hence, it can be considered as a novel technique for local drug delivery systems in endodontic management.

Intratumoral implantable drug delivery system for targeted localized chemotherapy in breast cancer

Breast cancer is a significant concern for many women, and local chemotherapy has emerged as a promising approach to address this issue. This study focuses on simulating the performance of chemotherapy using Doxorubicin, Cisplatin, Fluorouracil, and Methotrexate loaded in a dual release implantable system within a mathematical framework. The drugs are loaded in the implant as two forms: as free agents and encapsulated in nanoparticles. The results demonstrate that the elimination rate through blood microvessels and the diffusion mechanism play a crucial role in determining the bioavailability and effective penetration depth of the therapeutic agents. Drugs with high elimination rates, such as Doxorubicin, Cisplatin, and Fluorouracil, exhibit improved penetration depth by approximately 4, 3.75, and 2.25 times when encapsulated in small nanoparticles that release their content in the extracellular space. On the other hand, Methotrexate, with its weak removal rate, maintains a sufficient penetration depth and effective concentration level even as a free drug in the extracellular space. Therefore, encapsulating Methotrexate does not significantly impact on tumor penetration. This study emphasizes the potential of the dual implantable system as an effective approach for chemotherapy, particularly when considering the specific chemotherapy drug and the method of loading the therapeutic agent. The system proves to be particularly beneficial in tumors with low microvascular density. These findings provide valuable insights for future research in the development of local drug delivery systems for breast cancer treatment.

Biochemical implications of robotic surgery: a new frontier in the operating room.

Robotic surgery represents a milestone in surgical procedures, offering advantages such as less invasive methods, elimination of tremors, scaled motion, and 3D visualization. This in-depth analysis explores the complex biochemical effects of robotic methods. The use of pneumoperitoneum and steep Trendelenburg positioning can decrease pulmonary compliance and splanchnic perfusion while increasing hypercarbia. However, robotic surgery reduces surgical stress and inflammation by minimizing tissue trauma. This contributes to faster recovery but may limit immune function. Robotic procedures also limit ischemia-reperfusion injury and oxidative damage compared to open surgery. They also help preserve native antioxidant defenses and coagulation. In a clinical setting, robotic procedures reduce blood loss, pain, complications, and length of stay compared to traditional procedures. However, risks remain, including device failure, the need for conversion to open surgery and increased costs. On the oncology side, there is still debate about margins, recurrence, and long-term survival. The advent of advanced technologies, such as intraoperative biosensors, localized drug delivery systems, and the incorporation of artificial intelligence, may further improve the efficiency of robotic surgery. However, ethical dilemmas regarding patient consent, privacy, access, and regulation of this disruptive innovation need to be addressed. Overall, this review sheds light on the complex biochemical implications of robotic surgery and highlights areas that require additional mechanistic investigation. It presents a comprehensive approach to responsibly maximize the potential of robotic surgery to improve patient outcomes, integrating technical skill with careful consideration of physiological and ethical issues.

In Vitro Glioblastoma Model on a Plate for Localized Drug Release Study from a 3D-Printed Drug-Eluted Hydrogel Mesh.

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that has limited treatment options. Current standard therapies, including surgery followed by radiotherapy and chemotherapy, are not very effective due to the rapid progression and recurrence of the tumor. Therefore, there is an urgent need for more effective treatments, such as combination therapy and localized drug delivery systems that can reduce systemic side effects. Recently, a handheld printer was developed that can deliver drugs directly to the tumor site. In this study, the feasibility of using this technology for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) to treat glioblastoma is showcased. A flexible drug-loaded mesh (GlioMesh) loaded with poly (lactic-co-glycolic acid) (PLGA) microparticles is printed, which shows the sustained release of both drugs for up to a month. The effectiveness of the printed drug-eluting mesh in terms of tumor toxicity and invasion inhibition is evaluated using a 3D micro-physiological system on a plate and the formation of GBM tumoroids within the microenvironment. The proposed in vitro model can identify the effective combination doses of TMZ and DFP in a sustained drug delivery platform. Additionally, our approach shows promise in GB therapy by enabling localized delivery of multiple drugs, preventing off-target cytotoxic effects.

Mesoporous silica nanoparticles accommodating electrospun nanofibers as implantable local drug delivery system processed by cold atmospheric plasma and spin coating approaches

Nanofibers (NF) and nanoparticles are attractive for drug delivery to improve the drug bioavailability and administration. Easy manipulation of NF as macroscopic bulk material give rise to potential usages as implantable local drug delivery systems (LLDS) to overcome the failures of systemic drug delivery systems such as unmet personalized needs, side effects, suboptimal dosage. In this study, poly(ethylene glycol) polyethyleneimine (mPEG:PEI) copolymer blended poly ϵ-caprolactone NFs, NFblend accommodating mesoporous silica nanoparticles (MSN) as the implantable LLDS was achieved by employing spin coating and cold atmospheric plasma (CAP) as the post-process for accommodation on NFblend. The macroporous morphology, mechanical properties, wettability, and in vitro cytocompatibility of NFblend ensured their potential as an implantable LLDS and superior features compared to neat NF. The electron microscopy images affirmed of NFblend random fiber (average diameter 832 ± 321 nm) alignments and accessible macropores before and after MSN@Cur accommodation. The blending of polymers improved the elongation of NF and the tensile strength which is attributed as beneficial for implantable LLDS. CAP treatment could significantly improve the wettability of NF observed by the contact angle changes from ∼126° to ∼50° which is critical for the accommodation of curcumin-loaded MSN (MSN@Cur) and in vitro cytocompatibility of NF. The combined CAP and spin coating as the post-processes was employed for accommodating MSN@Cur on NFblend without interfering with the electrospinning process. The post-processing aided fine-tuning of curcumin dosing (∼3 µg to ∼15 µg) per dose unit and sustained zero-order drug release profile could be achieved. Introducing of MSN@Cur to cells via LLDS promoted the cell proliferation compared to MSN@Cur suspension treatments and assigned as the elimination of adverse effects by nanocarriers by the dosage form integration. All in all, NFblend-MSN@Cur was shown to have high potential to be employed as an implantable LLDS. To the best of our knowledge, this is the first study in which mPEG:PEI copolymer blend NF are united with CAP and spin coating for accommodating nano-drug carriers, which allows for NF both tissue engineering and drug delivery applications.

Hemicellulose-based nanoaggregate-incorporated biocompatible hydrogels with enhanced mechanical properties and sustained controlled curcumin release behaviors

Local drug delivery has generated considerable interest due to its controlled and sustained drug release at the target site on demand. Nanoaggregate-incorporated composite hydrogels are desirable as local drug delivery systems; however, it is difficult to achieve sustained and controlled hydrophobic drug release and superior mechanical properties in one system. Herein, a “smart” composite hydrogel was synthesized by incorporating hemicellulose-based nanoaggregates into a double network consisting of alginate/Ca2+ and polyacrylic acid-co-dimethylaminoethyl methacrylate [P(AA-co-DMAEMA)]. Hemicellulose-based nanoaggregates were assembled from xylan-rich hemicellulose laurate methacrylate (XH-LA-MA) polymers and entrapped into the hydrogel framework via chemical fixation. Another composite hydrogel with physically embedded hemicellulose laurate (XH-LA) nanoaggregates was prepared as a comparison. Accordingly, covalently cross-linked XH-LA-MA nanoaggregates in hydrogels resulted in a denser pore structure and reinforced mechanical properties. Nanoaggregate diffusion analysis revealed that covalent bonding between the nanoaggregates and the hydrogel framework contributed to prolonged diffusion behavior. Curcumin (Cur)-loaded XH-LA-MA composite hydrogels enabled sustained Cur release in simulated body fluid and showed stimulus responsiveness toward ethylenediaminetetraacetic acid (EDTA) and/or glutathione (GSH). All the composite hydrogels were biocompatible, as verified by Cell Counting Kit-8 (CCK-8) assay against NIH/3T3 cells. These composite hydrogels hold great potential as a promising dosage form for biomedical applications.

Pharmacokinetic Interpretation of Applying Local Drug Delivery System for the Treatment of Deep Surgical Site Infection in the Spine.

Surgical site infections (SSIs) after spinal surgery present significant challenges, including poor antibiotic penetration and biofilm formation on implants, leading to frequent treatment failures. Polymethylmethacrylate (PMMA) is widely used for localized drug delivery in bone infections, yet quantifying individual drug release kinetics is often impractical. This retrospective study analyzed 23 cases of deep SSIs (DSSIs) following spinal surgery treated with antibiotic-loaded PMMA. A mathematical model estimated personalized drug release kinetics from PMMA, considering disease types, pathogens, and various antibiotics. The study found that vancomycin (VAN), ceftriaxone (CRO), and ceftazidime (CAZ) reached peak concentrations of 15.43%, 15.42%, and 15.41%, respectively, within the first two days, which was followed by a lag phase (4.91-4.92%) on days 2-3. On days 5-7, concentrations stabilized, with CRO at 3.22% and CAZ/VAN between 3.63% and 3.65%, averaging 75.4 µg/cm2. Key factors influencing release kinetics include solubility, diffusivity, porosity, tortuosity, and bead diameter. Notably, a patient with a low glomerular filtration rate (ASA IV) was successfully treated with a shortened 9-day intravenous VAN regimen, avoiding systemic complications. This study affirms the effectiveness of local drug delivery systems (DDS) in treating DSSIs and underscores the value of mathematical modeling in determining drug release kinetics. Further research is essential to optimize release rates and durations and to mitigate risks of burst release and tissue toxicity.

Using embossing ice particulate method to prepare polyvinyl alcohol/pullulan hydrogels with surface open pores loaded with microspheres for breast cancer treatment

In the post-operative treatment of breast cancer, early prevention of locoregional recurrence is crucial to avoid metastasis of cells from leftover microtumor tissues. The limitations in conventional drug delivery systems show a growing clinical demand for disease-specific drug-releasing systems. This study explores a novel poly(vinyl alcohol)/pullulan (PVA/PUL) hydrogel system for local drug delivery in post-operative breast cancer treatment. Hydrogel was produced by combination of lyophilization and embossing ice particulate techniques to create microspheres loaded open pores on the hydrogel surface for localized release of doxorubicin-loaded polycaprolactone microspheres (DOX-PCL-MSs). PVA/PUL hydrogel was successfully crosslinked with glutaraldehyde and stabilized hydrogel structure has possessed slow degradation rate and increasing water retention through 12 days. Release of DOX after 7 and 16 days from DOX-PCL-MSs loaded hydrogels were slower with a 6.2 ± 8.9 % and 56.6 ± 4.5 % release compared to 60.9 ± 14.6 % and 76.8 ± 19.7 % release from free DOX loaded hydrogel since DOX release was controlled by PCL microspheres. When interacted with human breast cancer cell line (MCF-7), DOX-PCL-MSs were able to disrupt cell and spheroid morphology after 7 days at concentrations as low as 12 μg/mL loaded DOX. In vitro cytotoxicity study has showed that, DOX-PCL-MSs loaded hydrogel was able to decrease MCF-7 viability after 7 days of incubation with controlled release of DOX. While free DOX releasing hydrogel has lost cytotoxic activity even after 4 days of incubation. Furthermore, ability of PVA/PUL hydrogel to support L929 cell attachment was shown in the study, suggesting hydrogels potential for promoting tissue regeneration after anti-cancer treatment. The study reveals that PVA/PUL hybrid hydrogels loaded with DOX-PCL-MSs has impactful potential in post-surgical treatment of breast cancer.

A novel natural polysaccharide dissolving microneedle capable of adsorbing pus to load EGCG for the treatment of acne vulgaris

Acne vulgaris is a common inflammatory skin disease associated with Propionibacterium acnes (P. acnes), with serious physical and psychological effects on patients. Conventional topical use of antibiotics is not effective due to the skin barrier and oral administration can adversely affect the intestinal flora. Microneedle is a novel type of localized drug delivery system that noninvasively breaks through the stratum corneum barrier and effectively enhances the transdermal absorption of drugs. Here, Bletilla striata polysaccharide (BSP)/Hyaluronic acid (HA) loaded Epigallocatechin gallate (EGCG) was used as the microneedle body to easily penetrate the epidermis and enhance antibacterial ability. Polyvinyl alcohol (PVA) and Diatomaceous earth (DE) are used as the microneedle backing to absorb pus and bacterial debris, prevent re-infection of bacteria and promote skin healing. Compared to traditional antibiotics, the excellent skin permeability of EGCG@BSP/HA MNs studied here can improve the efficacy and solve side effects and drug resistance. In vivo studies in mice models induced by P. acnes showed that this microneedle could effectively reduce skin swelling, inhibit bacterial growth and reduce the levels of TNF-α, IL-8 and MMP-2. In summary, this study provides an ideal antimicrobial drug delivery system for the treatment of acne vulgaris.

LEVERAGING THE HEDGEHOG SIGNALLING PATHWAY TO IMPROVE TENDON-TO-BONE INTEGRATION

Despite extensive research aimed at improving surgical outcomes of enthesis injuries, re-tears remain a common problem, as the repairs often lead to fibrovascular scar as opposed to a zonal enthesis. Zonal enthesis formation involves anchoring collagen fibers, synthesizing proteoglycan-rich fibrocartilage, and mineralizing this fibrocartilage [1]. During development, the hedgehog signaling pathway promotes the formation and maturation of fibrocartilage within the zonal tendon-to-bone enthesis [1-4]. However, whether this pathway has a similar role in adult zonal tendon-to-bone repair is not known. Therefore, we developed a murine anterior cruciate ligament (ACL) reconstruction model [5] to better understand the zonal tendon-to-bone repair process and perturb key developmental regulators to determine the extent to which they can promote successful repair in the adult. In doing so, we activated the hedgehog signaling pathway both genetically using transgenic mice and pharmacologically via agonist injections. We demonstrated that both treatments improved the formation of zonal attachments and tunnel integration strength [6]. These improved outcomes were due in part to hedgehog signaling's positive role in proliferation of the bone marrow stromal cell (bMSC) progenitor pool and subsequent fibrocartilage production of bMSC progeny cells that form the attachments. These results suggest that, similar to growth and development, hedgehog signaling promotes the production and maturation of fibrocartilage during tendon-to-bone integration in adults. Lastly, we developed localized drug delivery systems to further improve the treatment of these debilitating injuries in future translational studies.Acknowledgements: This work was supported by NIH R01AR076381, R21AR078429, R00AR067283, F31AR079840, T32AR007132, and P30AR069619, in addition to the McCabe Fund Pilot Award at the University of Pennsylvania.

Design and synthesis of berberine loaded nano-hydroxyapatite/gelatin scaffold for bone cancer treatment

A tissue engineered BBR-loaded nano-HA/gelatin scaffold, as a local drug delivery system, was developed with the aim to be implanted after surgery for osteosarcoma treatment, mimicking the natural tissue ECM, and releasing BBR as an anticancer drug.

Chitosan- A Promising agent for site specific drug delivery in periodontics

Periodontal diseases are chronic infectious illnesses that have become a significant burden on oral health. Several new treatment targets have been found because of advances in the study of the epidemiology, aetiology, and pathophysiology of periodontitis, as well as the analysis of the polymicrobial interaction in the oral bacterial communities. Efforts to limit growth of bacteria and the formation of substances that eventually damage the tissues supporting the teeth have been the foundation of periodontal therapy. Systemic antibiotic administration for periodontitis has significant shortcomings, attracting attentiontowards the advancement of localized drug delivery systems capable ofmaintaining effective antibiotic concentrations at the intended site throughout the course of treatment with minimum side effects. A controlled release system that can be placed within the periodontal pocket so as to extend therapeutic concentrations at the desired site at a considerably lesser dosage is a pressing priority. Chitosan, a potential carbohydrate biopolymer, is receiving scientific interest in a diverse range of biomedical fields due to its exceptional chemical and pharmacokinetic attributes. Chitosan is a biocompatible and biodegradable naturally occurring polysaccharide with several uses in dentistry owing to its functional versatility and easy accessibility. The applications of chitosan are vast, exciting, and still unexplored. Thisreviewfocusesonthe potential uses of chitosan in periodontology.

Evaluation of Different Local Drug Delivery Systems in Treatment of Periodontitis: An Institutional Study

Periodontal disease can be treated in both non-surgical and surgical therapy. There could be a possible reason why non-surgical therapy causes failure due to bacteria virulent factors and also the depth of periodontal pocket is greater than the instrumentation available, drug concentration is low in GCF as well as in saliva. To overcome this problem a treatment protocol that would include short-term usage of systemic and or local antimicrobial agents is being tried as an adjunct to mechanical therapy in treatment of periodontal diseases. A total of 540 sites, from 72 patients in different quadrants of the mouth received these treatment modalities in assigned quadrants such as scaling and root planning using both hand and ultrasonic instruments under local anesthesia (if required), combination therapy and local drug delivery alone. Patients with periodontal diseased sites were divided into five groups, based on the local drug delivery system, as Group I: Elyzol (25% Metronidazole), Group II: Dentomycin (2% Minocycline hydrochloride), Group III: Metrogene (5% Metronidazole), Group IV: Periochip (2.5mg of Chlorhexidine gluconate) and Group V: Atridox (10% Doxycycline hyclate). In the present study, the bleeding index score showed better reduction, for all LDD systems. The results showed that SRP alone, and LDD alone had shown no significance in overall reduction of pocket depth where clinical parameters (Plaque Index, Gingival Bleeding Index and Gingival Index). Although the combined treatment of scaling and root planing plus the local drug therapy reported to have a significant benefit over SRP alone in the treatment of periodontal lesions. Keywords: Anti-Bacterial Agents, Metronidazole, Minocycline, Doxycycline, Chlorhexidine, Local Drug Delivery Systems, Humans, Periodontitis, Periodontal Pocket, Root Planing

Efficacy of Probiotics Versus Tetracycline Fibers as Adjuvants to Scaling and Root Planing on Interleukin 1β Levels in Type 2 Diabetic Patients With Periodontitis: A Clinical and Biochemical Study.

Background Periodontitis, a chronic inflammatory disease, is triggered by the plaque biofilm culminating in periodontal attachment loss, bone loss, and tooth loss. Diabetes, a globally prevalent disease, causes an increased inflammatory response to the microflora associated with periodontitis. It has been observed that the link between these two diseases is bidirectional. Tissue repair is impaired in diabetic patients with periodontitis. Local drug delivery systems selectively target the inflamed sites contrary to systemic antibiotics which lead to resistance and many other adverse effects.Probiotics aid in the growth of beneficial microorganisms and have immunomodulatory effects on the host. Tetracyclines have anti-collagenase properties and reduce the bacterial load, curbing the progression of periodontitis. Interleukin (IL) 1β, a strong marker of periodontal tissue destruction, plays a pivotal role in inflammation, immune regulation, and bone resorption in periodontitis. This study evaluated and compared the benefits of probiotics and tetracycline fibers when used as adjunctive tools after scaling and root planing (SRP) on IL1β levels in type 2 diabetic patients with periodontitis. Methodology A total of 36 patients participated in this study. Group I included 12 patients with periodontitis and uncontrolled diabetes (HbA1c levels >7). After SRP, six patients received tetracycline fibers (IA), and six patients received probiotics (1B) as locally delivered agents. Group II included 12 patients with periodontitis and diabetes under control (HbA1c levels 6-7%). After SRP, six patients received tetracycline fibers (IIA), and six patients received probiotics (IIB) as locally delivered drugs (test groups). Group III, the control group, included 12 patients with periodontitis only, wherein a placebo was used as a local drug delivery (LDD) after SRP. The clinical parameters, such as plaque index, gingival index, and probing pocket depth, were recorded preoperatively and at eight and 12 weeks after non-surgical periodontal therapy. IL1β levels were assessed by enzyme-linked immunosorbent assay at baseline and six weeks after SRP. Results On intra and intergroup comparison, all groups showed improvement in both the clinical and biochemical parameters but significant results were seen in Group IIA (p < 0.01) when compared to the other groups. Conclusions Group II (well-controlled diabetics) performed significantly better than the other groups, which was followed by Group III. The use of LDDs as adjunctive tools after SRP was not beneficial in Group I (uncontrolled diabetics).

Investigation of cellulose acetate electrospun films for controlled drug permeability

The current work examined the capability of electrospun film to act as a membrane for controlling drug permeability for its intended application in local drug delivery systems. Electrospun films of cellulose acetate were chosen as the model to utilize Taguchi design of experiment (DoE) that took into account the independent input variables (applied voltage, flow rate, collector distance and polymer concentration). Drug permeability and tensile strength were chosen as the response parameters. Applied voltage of 27 kV, flow rate of 1.25 mL/h, collector distance of 12.5 cm and polymer concentration of 19 % were found to be the ideal combination for higher tensile strength and lower drug permeability. The results of the analysis of variance (ANOVA) revealed that, among the input parameters examined, polymer concentration was the most influencing for both the response parameters. The analysis of fiber morphology, fiber orientation and porosity of electrospun was also performed. The results indicated the ability of electrospun fiber to achieve drug permeability as low as 31.7 % (in initial 24 h) and highest tensile strength of 3.81 MPa.