Local Drug Delivery Research Articles

Biocompatible ionic liquid self-assembled transdermal delivery system (P-M IL/AKE) for significantly improved skin photoaging and reduced wrinkles

Most peptide drugs have good biological activity and safety, but their stability and permeability are poor, limiting their applications in the field of local drug delivery. Snake venom peptide (AKE) is a tripeptide with good anti-wrinkle effects, but its weak esterophilicity, poor penetration, and low bioavailability limit its full anti-wrinkle potential. To address this issue, a bioactive ionic liquid (P-M IL) was prepared and an efficient self-assembled peptide drug delivery system was constructed through AKE loading, which increased the cumulative absorption of AKE in the skin by more than five-fold, resulting in good biocompatibility. Further, P-M IL/AKE can significantly increase collagen protein secretion by human fibroblasts, improved skin photoaging and reduce the areas and volume of wrinkle in the eye tail lines. In addition, for the first time, quantum chemical calculations, homology modeling, molecular docking and binding free energy calculations were used to analyze the structural stability of the system, construct the 3D model, explore the interaction mode and reveal the theoretical basis of anti-wrinkle effect. Therefore, this supramolecular self-assembled transdermal drug delivery system has potential advantages, providing a novel approach for the highly efficient and non-invasive delivery of peptide drugs.

Injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel for local treatment of osteomyelitis: Fabrication, characterization, and in vitro performance evaluation.

The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas-Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against Staphylococcus aureus for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.

X-ray Opaque Polymer Drug-Eluting Beads Loaded with Iodized Oil: Preparation and In Vitro and In Vivo Evaluations.

Drug-eluting microspheres are commonly used as a local drug delivery system for interventional therapy. However, current drug-eluting microspheres have poor X-ray visibility, which can hinder tracking and postembolization evaluation. In the current study, X-ray-visible poly(acrylic acid) drug-eluting beads loaded with iodized oil (IO-PAA-DEBs) ranging from 100-300 μm were prepared and evaluated both in vitro and in vivo. Iodized oil served as the radiopaque agent, and X-ray and computed tomography scanning confirmed that the microspheres exhibited excellent X-ray-visible properties. The drug-loading capacities of bleomycin hydrochloride, doxorubicin hydrochloride, and oxaliplatin were also investigated. IO-PAA-DEBs exhibited sustained drug release properties, accompanied by a cumulative drug release rate that reached approximately 60% after 120 h. In vitro and in vivo experiments revealed that IO-PAA-DEBs had good biocompatibility. Collectively, these results demonstrated that IO-PAA-DEBs could facilitate transarterial embolization and sustained drug delivery.

Targeted Delivery of Nanoparticles to Blood Vessels for the Treatment of Atherosclerosis.

Atherosclerosis is a common form of cardiovascular disease, which is one of the most prevalent causes of death worldwide, particularly among older individuals. Surgery is the mainstay of treatment for severe stenotic lesions, though the rate of restenosis remains relatively high. Current medication therapy for atherosclerosis has limited efficacy in reversing the formation of atherosclerotic plaques. The search for new drug treatment options is imminent. Some potent medications have shown surprising therapeutic benefits in inhibiting inflammation and endothelial proliferation in plaques. Unfortunately, their use is restricted due to notable dose-dependent systemic side effects or degradation. Nevertheless, with advances in nanotechnology, an increasing number of nano-related medical applications are emerging, such as nano-drug delivery, nano-imaging, nanorobots, and so forth, which allow for restrictions on the use of novel atherosclerotic drugs to be lifted. This paper reviews new perspectives on the targeted delivery of nanoparticles to blood vessels for the treatment of atherosclerosis in both systemic and local drug delivery. In systemic drug delivery, nanoparticles inhibit drug degradation and reduce systemic toxicity through passive and active pathways. To further enhance the precise release of drugs, the localized delivery of nanoparticles can also be accomplished through blood vessel wall injection or using endovascular interventional devices coated with nanoparticles. Overall, nanotechnology holds boundless potential for the diagnosis and treatment of atherosclerotic diseases in the future.

5-Fluoro uracil mediated transformation of surface-active ionic liquid based micellar nanoaggregates into pH-responsive vesicular nanoaggregates as promising drug delivery vehicle

Surface-active ionic liquids (SAILs) are poised as significant contenders in sustained and targeted drug delivery due to their membrane-like structures and their ability to transport drug molecules regardless of their polarity. In order to design a simple system that an encapsulate the anticancer drug and release it in a sustained manner, herein we designed vesicular nano-aggregates through synergistically interacting chemotherapeutic drug 5-Fluoro Uracil (5-FU) with the biocompatible SAILs, Choline Oleate ([Ch][Ol]) and Tetramethyl guanidine Oleate ([TMG][Ol]). The intention for designing the system is to offers less complexity and improved drug loading efficiency and targeted and sustained release. The molecular interactions have been proven by computational approach and the size of the nanoaggregates was determined using techniques such as Dynamic Light Scattering (DLS), Förster Resonance Energy Transfer (FRET) and Small-Angle Neutron Scattering (SANS). SANS fitting data and TEM images confirmed the transition of prolate ellipsoid micelles at [5-FU] = 0 mM to uni-lamellar ([5-FU] = 1 mM) and multi-lamellar vesicles ([5-FU] = 2 mM). These vesicular nano-aggregates are studied for their stability against temperature, pH-response and ionic strength of solution, revealing stability up to 60 °C, robust at physiological pH 7.4 and remain stable to exposure to Na+ and Ca2+ ions at concentrations up to 180 mM and 50 mM, respectively. The vesicular nano-aggregates ([Ch][Ol]/5-FU and [TMG][Ol]/5-FU) when exposed to physiological pH (i.e., 7.4) released 64.8 % and 61.2 % drug release whereas when the same systems were exposed to cancerous pH (5.2 and 6.7) released 95.9 % and 84.5% (pH 5.2 and 6.7) and 94.8 % and 81.2 % (pH 5.2 and 6.7) for the [Ch][Ol]/5-FU and [TMG][Ol]/5-FU systems, respectively. Results for the studied system encompasses them as a promising candidate for drug release at specific sites. The anticipated research might pave the way for the development of a biocompatible and stimuli-responsive drug carrier that would allow for the localized delivery of an anticancer drug.

Fabrication and Characterization of Electrospun Ocimum sanctum and Curcumin-Loaded Nanofiber Membrane for the Management of Periodontal Disease: An In Vitro Study.

Background Periodontal disease is a chronic inflammatory condition that gradually deteriorates the supportive tissues of teeth, eventually leading to tooth loss. Mechanical debridement stands as the gold standard method for treating periodontitis. However, antimicrobial therapy is recommended for optimal results when used alongside mechanical debridement. Numerous studies have investigated local drug delivery as an adjunct to mechanical debridement of affected tooth surfaces. Ocimum sanctum exhibits anti-inflammatory, antioxidant, and antimicrobial properties. Similarly, curcumin, as documented in the literature, demonstrates a broad spectrum of anti-inflammatory and antimicrobial effects. Electrospinning has demonstrated itself to be a highly effective method for fabricating drug-loaded fibers. Electrospun nanofibers containing Ocimum sanctum and curcumin are expected to exhibit greater efficacy due to their increased surface area, facilitating the dispersion of larger quantities of drugs, and their ability to control drug release when employed as a local drug delivery system. This study aims to fabricate and characterize the properties of nanofiber membranes loaded with Ocimum sanctum and curcumin using the electrospinning technique. Methods About 50 mg each of Ocimum sanctum and curcumin were blended with 15% polyvinyl alcohol and 2% chitosan polymer in a 4:1 ratio and left to stir overnight. A 10 mL syringe was filled with this solution, and an 18 G blunt-end needle charged at 15.9 kV was used for extrusion. Continuous fibers were collected onto a collector plate positioned 12 cm from the center of the needle tip, at a flow rate of 0.005 mL/min. The morphology of the fabricated membrane was assessed through scanning electron microscopy (SEM), the strength of the material was assessed through tensile strength analysis using INSTRON, an Electropuls E3000 Universal Testing Machine(INSTRON, Norwood, MA), and the drug release pattern was analyzed using Jasco V-730 UV-visible spectrophotometer(Jasco, Easton, MD). Results The morphology of this nanofiber showed a random distribution of fibers with no bead formation. The average diameter of the membrane was 383±102 nm, and the tensile strength of this material was 1.87 MPa. The drug release pattern showed an initial burst release of Ocimum sanctum, followed by a controlled release in subsequent hours. However, curcumin showed very little drug release because of its solubility. Conclusion In summary, the Ocimum sanctum and curcumin-loaded nanofibers exhibited robust tensile strength, a controlled drug release profile, and uniform drug distribution within the nanofiber membrane. Consequently, it can be concluded that curcumin nanofibers and electrospun Ocimum sanctum serve as valuable agents for local drug delivery in the treatment of periodontitis.

Modifications of Nanobubble Therapy for Cancer Treatment.

Cancer development is related to genetic mutations in primary cells, where 5-10% of all cancers are derived from acquired genetic defects, most of which are a consequence of the environment and lifestyle. As it turns out, over half of cancer deaths are due to the generation of drug resistance. The local delivery of chemotherapeutic drugs may reduce their toxicity by increasing their therapeutic dose at targeted sites and by decreasing the plasma levels of circulating drugs. Nanobubbles have attracted much attention as an effective drug distribution system due to their non-invasiveness and targetability. This review aims to present the characteristics of nanobubble systems and their efficacy within the biomedical field with special emphasis on cancer treatment. In vivo and in vitro studies on cancer confirm nanobubbles' ability and good blood capillary perfusion; however, there is a need to define their safety and side effects in clinical trials.

Herbal Local Drug Delivery: A Narrative Review

Abstract Periodontitis is a complex and chronic inflammation of the periodontium and can be diagnosed clinically by gingival inflammation, attachment loss, and loosening of teeth. Both nonsurgical and surgical periodontal therapies are used to treat periodontal diseases. However, in some cases, solely mechanical therapy is ineffective, especially in inaccessible areas. Hence, in such cases, systemic and local drug therapy is well-advised adjuvant to scaling and root planning. Local drug therapy provides specificity at the site of infection. Various antimicrobial agents are used for local applications into periodontal pockets such as chlorhexidine and tetracycline; however, these drugs have certain adverse reactions. To overcome these unfavorable side effects, herbal extracts came into the limelight. Therefore, this review gives an insight into the properties and benefits of natural extracts used as local drug delivery for periodontal treatment.

Mucosa-penetrating liposomes for esophageal local drug delivery

Local drug delivery to the esophagus is hampered by rapid transit time and poor permeability of the mucosa. If some strategies aimed to improve the residence time have been proposed, non-invasive approaches to increase the drug penetration in the mucosa have not been described so far. Herein, we designed mucosa-penetrating liposomes to favor the penetration and retention of curcumin (CURC) in the esophagus. A novel mucosa penetrating peptide (MPP), SLENKGP, was selected by Phage Display and conjugated to pegylated liposomes at different PEG and MPP’s surface densities. Pegylation assured a long residence time of liposomes (at least 30 min) in the esophagus in vivo, but it did not favor the penetration of CURC in the mucosa. MPP-decorated liposomes instead delivered a significant higher amount of CURC in the mucosa compared to naked pegylated liposomes. Confocal microscopy studies showed that naked pegylated liposomes remain confined in the superficial layers of the mucosa whereas MPP-decorated liposomes penetrate the whole epithelium. In vitro, MPP reduced the interaction of PEG with mucin, meanwhile favoring the paracellular penetration of liposomes across epithelial cell multilayers. In conclusion, pegylated liposomes represent a valid approach to target the esophagus and the surface functionalization with MPP enhances their penetration in the mucosa.

The adjunctive effect of subgingival application of probiotics versus spirulina to nonsurgical treatment of stage II grade B periodontitis: a randomized controlled clinical trial

Abstract Aim The use of natural remedies as local drug delivery has grown recently since they are generally safe and have shown promising outcomes in the management of periodontitis. The purpose of this study was to evaluate the effectiveness of spirulina gel and probiotics as supplements for scaling and root planing (SRP). Patients and methods Thirty individuals with periodontitis (stage II, grade B) were divided into three groups at random: group I (GI) received a subgingival application of probiotic (Lactobacillus reuteri) suspension after SRP. Group II (GII) had SRP, then spirulina gel was applied. Group III (GIII) was used as a control that received SRP and placebo gel using a blunt syringe at baseline, 1, 2, and 4 weeks. Gingival index (GI), probing pocket depth, clinical attachment level (CAL), and gingival crevicular fluid nitric oxide level were assessed at baseline, 3, and 6 months. Results Compared to the baseline value, the three treatments led to a statistically significant decrease in GI, probing pocket depth, and clinical attachment level gain after 3 and 6 months (P < 0.05). Comparing the groups to each other’s, there were significant differences between them, whereas both GI and GII showed statistically significant differences when compared to GIII (the control group). All treatment modalities resulted in a statistically significant reduction in the gingival crevicular fluid level of NO, but group II showed the best effect on the inhibition of the nitric oxide level. Conclusion Local application of probiotics and spirulina is safe and effective as adjunctive treatment to SRP in the treatment of stage II, grade B periodontitis.

Magnetically triggered ingestible capsule for localized microneedle drug delivery

Magnetically triggered ingestible capsule for localized microneedle drug delivery

TiO2 nanotubes with customized diameters for local drug delivery systems

AbstractIn this study, we evaluated the drug release behavior of diameter customized TiO2 nanotube layers fabricated by anodization with various applied voltage sequences: conventional constant applied potentials of 20 V (45 nm) and 60 V (80 nm), a 20/60 V stepped potential (50 nm [two‐diameter]), and a 20–60 V swept potential (49 nm [full‐tapered]) (values in parentheses indicate the inner tube diameter at the top part of nanotube layers). The structures of the 50 nm (two‐diameter) and 49 nm (full‐tapered) samples had smaller inner diameters at the top part of nanotube layers than that of the 80 nm sample, while the outer diameters at the bottom part of nanotube layers were almost the same size as the 80 nm sample. The 80 nm sample, which had the largest nanotube diameter and length, exhibited the greatest burst release, followed by the 50 nm (two‐diameter), 49 nm (full‐tapered), and 45 nm samples. The initial burst released drug amounts and release rates from the 50 nm (two‐diameter) and 49 nm (full‐tapered) samples were significantly suppressed by the smaller tube top. On the other hand, the largest proportion of the slow released drug amount to the total released drug amount was observed for the 50 nm (two‐diameter) sample. Thus, 50 nm (two‐diameter) achieved suppressed initial burst release and large storage capacity. Therefore, this study has, for the first time, applied TiO2 nanotube layers with modulated diameters (two‐diameter and full‐tapered) to the realization of a localized drug delivery system (LDDS) with customized drug release properties.

Microglial MyD88-dependent pathways are regulated in a sex-specific manner in the context of HMGB1-induced anxiety.

Chronic stress is a significant risk factor for the development and recurrence of anxiety disorders. Chronic stress impacts the immune system, causing microglial functional alterations in the medial prefrontal cortex (mPFC), a brain region involved in the pathogenesis of anxiety. High mobility group box 1 protein (HMGB1) is an established modulator of neuronal firing and a potent pro-inflammatory stimulus released from neuronal and non-neuronal cells following stress. HMGB1, in the context of stress, acts as a danger-associated molecular pattern (DAMP), instigating robust proinflammatory responses throughout the brain, so much so that localized drug delivery of HMGB1 alters behavior in the absence of any other forms of stress, i.e., social isolation, or behavioral stress models. Few studies have investigated the molecular mechanisms that underlie HMGB1-associated behavioral effects in a cell-specific manner. The aim of this study is to investigate cellular and molecular mechanisms underlying HMGB1-induced behavioral dysfunction with regard to cell-type specificity and potential sex differences. Here, we report that both male and female mice exhibited anxiety-like behavior following increased HMGB1 in the mPFC as well as changes in microglial morphology. Interestingly, our results demonstrate that HMGB1-induced anxiety may be mediated by distinct microglial MyD88-dependent mechanisms in females compared to males. This study supports the hypothesis that MyD88 signaling in microglia may be a crucial mediator of the stress response in adult female mice.

Review on Colon Targeted Drug Delivery System

This review focuses on the importance of local drug delivery in the treatment of Gastro intestinal diseases ulcerative colitis, Crohn’s disease, amebiasis, colon cancer. For many types of drugs, oral administration is the most common route of administration due to patient compliance and flexibility. Targeted drug delivery system is a system that sends drugs to diseased areas by changing the amount of information. The large intestine is where local drug delivery and systemic diseases can occur. Treatment will be better if the drug directly targets the intestine. The large intestine is where the local child allows local treatment of intestinal diseases and the distribution of drugs. Gastrointestinal therapeutic drugs are effective when they can be directly targeted to the intestine, because drug release and absorption should not occur in the stomach and small intestine and the bioactive agents should not be broken down and released into the intestine. Drugs targeting the intestinal area not only affect the treatment of local diseases, but also deliver drugs such as proteins and peptides to the body due to their effects on the body. At the same time, due to weakness of the digestive system, these drugs are broken down and their availability is quiet low.

Curcumin analogue AC17-loaded dissolvable microneedles activate FOXO3 and enhance localized drug delivery for oral squamous cell carcinoma treatment

Curcumin, a polyphenol extracted from turmeric, is a potential alternative for the treatment of oral squamous cell carcinoma (OSCC) due to its remarkable anticancer activity and low systemic toxicity. To further enhance the anticancer activity and bioavailability of curcumin, we synthesized a curcumin analogue, AC17, by modifying the benzene ring and methylene group of curcumin. A soluble hyaluronic acid microneedle patch (AC17@HAMN) was developed to ensure accurate and safe delivery of AC17 to tumor tissues. The inhibitory effect of AC17 on OSCC cells was stronger than that of curcumin and some common analogues. Transcriptome sequencing showed that the target genes of AC17 were mainly concentrated in apoptosis, cell cycle and cell senescence pathways. Among them, AC17 induces cell cycle arrest and inhibits cell proliferation mainly by activating FOXO3 signaling. With good penetration and dissolution properties, microneedles can deliver AC17 directly to the tumor site and show good anti-tumor effect. Moreover, AC17@HAMN showed good biosafety. In summary, AC17@HAMN offers high efficiency, minimal invasiveness, and few adverse reactions. This microneedle patch holds great promise for potential clinical applications, especially for the treatment of OSCC.

Efficacy of Locally Delivered Herbal Chip Containing (8% Mimusops elengi) as an Adjunct to Scaling and Root Planing in Chronic Periodontitis: A Randomised Split-mouth Clinical Study

Introduction: Conventional mechanical debridement does not remove all pathogenic bacteria from the subgingival environment. To overcome these limitations, local drug delivery systems enhance the curative effect by combining with drugs, which promote bone and tissue regeneration. Thus, this study aims to evaluate the efficacy of locally delivered herbal chips containing (8% Mimusops elengi) as an adjunct to scaling and root planing (SRP) and compared to SRP alone for the treatment of chronic periodontitis. Materials and Methods: A randomised split-mouth clinical study was conducted among chronic periodontitis patients undergoing periodontal therapy. Thirty subjects with 60 sites were divided into test and control groups. The control sites were treated with SRP alone, whereas the test sites were treated with SRP followed by placement of an 8% M. elengi herbal chip within the pockets. Patients were recalled on the 21st and 45th day, and clinical parameters were measured. Results: An inter-group comparison of all the clinical parameters between the control and test sides was statistically analysed. At all periods of the study, the mean difference was observed to be highly significant (P < 0.001). Conclusion: The 8% M. elengi chip is effective as an adjunct to non-surgical periodontal therapy in chronic periodontitis probing depth. Further clinical studies are needed to evaluate the long-term efficacy of M. elengi.

Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

SURG-02. INTRAOPERATIVE APPLICATION OF A POLYMER-BASED HYDROGEL AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL TERATOID/RHABDOID TUMOURS

Abstract BACKGROUND 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. To the best of our knowledge, they have not been investigated for the treatment of paediatric cerebellar tumours, including medulloblastoma group 3 (MB3) and atypical teratoid/rhabdoid tumours (ATRT), both of which are associated with poor prognoses. METHODS We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)-poly(ethyleneglycol) (PECE) hydrogel, which has been investigated broadly throughout the literature 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 ATRT 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 ATRT intracranial xenograft 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 ATRT, 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. CONCLUSIONS 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 ATRT, 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.

In Vivo Release of Zafirlukast from Electrospun Polyisobutylene-Based Fiber Mats to Reduce Capsular Contracture of Silicone Breast Prostheses.

Silicone rubber tissue expanders and breast implants are associated with chronic inflammation, leading to the formation of fibrous capsules. If the inflammation is left untreated, the fibrous capsules can become hard and brittle and lead to formation of capsular contracture. When capsular contracture occurs, implant failure and reoperation is unavoidable. Fibrous capsule formation to medical grade silicone rubber breast implants and polyisobutylene-based electrospun fiber mats attached to silicone rubber with and without an anti-inflammatory therapeutic were compared. A linear polyisobutylene (PIB)-based thermoplastic elastomer is currently applied as a polymer coating for drug release on coronary stents to reduce restenosis. Recent work has created a drug releasing electrospun fiber mat from PIB-based materials. Important to this study, poly(alloocimene-b-isobutylene-b-alloocimene) (AIBA) was electrospun with zafirlukast (ZAF). ZAF is an anti-inflammatory drug that is able to reduce capsule formation and complications to silicone breast implants. Fiber mats are advantageous for local drug delivery because of their high porosity and surface area for drug release. The chief hypothesis was that local release of ZAF from AIBA would lower inflammatory signaling and resulting capsular formation after 90 days in vivo. Electrospun AIBA mats locally released ZAF, lowering inflammation and fibrous capsule development compared to medical grade silicone rubber. Locally and orally released ZAF led to similar results, but the former had much lower concentration that highlights local delivery's therapeutic potential. Released ZAF from AIBA fiber mats mitigated inflammation and serves as an alternative to existing clinical approaches.

Scaffold-Mediated Drug Delivery for Enhanced Wound Healing: A Review.

Wound healing is a complex physiological process involving coordinated cellular and molecular events aimed at restoring tissue integrity. Acute wounds typically progress through the sequential phases of hemostasis, inflammation, proliferation, and remodeling, while chronic wounds, such as venous leg ulcers and diabetic foot ulcers, often exhibit prolonged inflammation and impaired healing. Traditional wound dressings, while widely used, have limitations such poor moisture retention and biocompatibility. To address these challenges and improve patient outcomes, scaffold-mediated delivery systems have emerged as innovative approaches. They offer advantages in creating a conducive environment for wound healing by facilitating controlled and localized drug delivery. The manuscript explores scaffold-mediated delivery systems for wound healing applications, detailing the use of natural and synthetic polymers in scaffold fabrication. Additionally, various fabrication techniques are discussed for their potential in creating scaffolds with controlled drug release kinetics. Through a synthesis of experimental findings and current literature, this manuscript elucidates the promising potential of scaffold-mediated drug delivery in improving therapeutic outcomes and advancing wound care practices.