Sustained Release of Antifungal and Antibacterial Agents from Novel Hybrid Degradable Nanofibers for the Treatment of Polymicrobial Osteomyelitis.

This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron microscopy, tensile testing, water contact angle analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The in vitro release of the antimicrobial agents was assessed using an elution method and a high-performance liquid chromatography assay. The in vivo elution pattern of nanofibrous mats was assessed using a rat femoral model. The experimental results demonstrated that the antimicrobial agent-loaded nanofibers released high levels of fluconazole, vancomycin, and ceftazidime for 30 and 56 days in vitro and in vivo, respectively. Histological assays revealed no notable tissue inflammation. Therefore, hybrid biodegradable PLGA nanofibers with a sustainable release of antifungal and antibacterial agents may be employed for the treatment of polymicrobial osteomyelitis.

Anti-Adhesive Resorbable Indomethacin/Bupivacaine-Eluting Nanofibers for Tendon Rupture Repair: In Vitro and In Vivo Studies.

The treatment and surgical repair of torn Achilles tendons seldom return the wounded tendon to its original elasticity and stiffness. This study explored the in vitro and in vivo simultaneous release of indomethacin and bupivacaine from electrospun polylactide-polyglycolide composite membranes for their capacity to repair torn Achilles tendons. These membranes were fabricated by mixing polylactide-polyglycolide/indomethacin, polylactide-polyglycolide/collagen, and polylactide-polyglycolide/bupivacaine with 1,1,1,3,3,3-hexafluoro-2-propanol into sandwich-structured composites. Subsequently, the in vitro pharmaceutic release rates over 30 days were determined, and the in vivo release behavior and effectiveness of the loaded drugs were assessed using an animal surgical model. High concentrations of indomethacin and bupivacaine were released for over four weeks. The released pharmaceutics resulted in complete recovery of rat tendons, and the nanofibrous composite membranes exhibited exceptional mechanical strength. Additionally, the anti-adhesion capacity of the developed membrane was confirmed. Using the electrospinning technique developed in this study, we plan on manufacturing degradable composite membranes for tendon healing, which can deliver sustained pharmaceutical release and provide a collagenous habitat.

Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum.

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide-polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.

Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle.

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

Sustained relief of pain from osteosynthesis surgery of rib fracture by using biodegradable lidocaine-eluting nanofibrous membranes.

Various effective methods are available for perioperative pain control in osteosynthesis surgery, but they are seldom applied intraoperatively. The aim of this study was to evaluate a biodegradable poly([d,l]-lactide-co-glycolide) (PLGA)/lidocaine nanofibrous membrane for perioperative pain control in rib fracture surgery. Scanning electron microscopy showed high porosity of the membrane, and an ex vivo high-performance liquid chromatography study revealed an excellent release profile for both burst and controlled release of lidocaine within 30days. Additionally, the PLGA/lidocaine nanofibrous membrane was applied in an experimental rabbit rib osteotomy model. Implantation of the membrane around the osteotomized rib during osteosynthesis surgery resulted in a significant increase in weight gain, food and water consumption, and daily activity compared to the study group without the membrane. In addition, all osteotomized ribs were united. Thus, application of the PLGA/lidocaine nanofibrous membrane may be effective for sustained relief of pain in oeteosynthesis surgery.

Preclinical experiments on the release behavior of biodegradable nanofibrous multipharmaceutical membranes in a model of four-wall intrabony defect.

Guided tissue regeneration (GTR) therapy has been widely used to regenerate lost periodontium from periodontal disease. However, in terms of regenerative periodontal therapy, a multidrug-loaded biodegradable carrier can be even more promising in dealing with periodontal disease. In the current study, we fabricated biodegradable nanofibrous collagen membranes that were loaded with amoxicillin, metronidazole, and lidocaine by an electrospinning technique. The in vitro release behavior and the cytotoxicity of the membranes were investigated. A four-wall intrabony defect was created in rabbits for in vivo release analysis. The bioactivity of the released antibiotics was also examined. The experimental results showed that the drug-loaded collagen membranes could provide sustainable release of effective amoxicillin, metronidazole, and lidocaine for 28, 56, and 8 days, respectively, in vivo. Furthermore, the bioactivity of the released antibiotics remained high, with average bioactivities of 50.5% for amoxicillin against Staphylococcus aureus and 58.6% for metronidazole against Escherichia coli. The biodegradable nanofibrous multipharmaceutical membranes developed in this study may provide a promising solution for regenerative periodontal therapy.

Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury.

Nonsurgical treatment and surgical repairment of injured Achilles tendons seldom restore the wounded tendon to its original elasticity and stiffness. Therefore, we hypothesized that the surgically repaired Achilles tendon can achieve satisfactory regeneration by applying multi-drug encapsulated hydrogels. In this study, a novel bupivacaine-eluting carbon dioxide-encapsulated Pluronic F127 hydrogel (BC-hydrogel) was developed for the treatment of Achilles tendon injuries. The rheological properties of BC-hydrogel were measured. A high-performance liquid chromatography assay was used to assess the release characteristics of bupivacaine in both in vitro and in vivo settings. Furthermore, the effectiveness of BC-hydrogel in treating torn tendons was examined in a rat model, and histological analyses were conducted. Evidently, the degradable hydrogels continuously eluted bupivacaine for more than 14 days. The animal study results revealed that the BC-hydrogel improved the post-surgery mobility of the animals compared with pristine hydrogels. Histological assay results demonstrated a significant reaction to high vascular endothelial growth factor in the surrounding tissues and expression of collagen I within the repaired tendon. This demonstrates the potential of this novel BC-hydrogel as an effective treatment method for Achilles tendon injuries.

In vitro and in vivo analysis of a biodegradable poly(lactide-co-glycolide) copolymer capsule and collagen composite system for antibiotics and bone cells delivery.

The authors investigated poly(lactide-co-glycolide) (PLGA) capsule and collagen composite system for antibiotics and bone cells delivery to treat infected bone defects. Poly(lactide-co-glycolide) was mixed with vancomycin and hot compressing molded to form an antibiotic capsule. Rabbit mesenchymal stem cells (MSCs) were entrapped in collagen gel phase and dispersed throughout the void volume of capsule. In vitro study, the composite systems were cultured in complete or osteogenic medium for 21 days. The profiles of vancomycin released from the systems were evaluated using the high-performance liquid chromatography method. Relative activity of vancomycin against Staphylococcus aureus was determined by an antibiotic disk diffusion method. The expression of osteogenic gene was determined by reverse-transcription polymerase chain reaction. The alkaline phosphatase activity and calcium level of the MSCs were assessed. Analytical results demonstrated that the concentrations of vancomycin eluted from the composite system were above the minimal inhibitory concentration for 21 days. Sample inhibition zone was 10 to 24 mm, and the relative activity was 17.6% to 100%. mRNA of Cbfa1 and osteocalcin were detected, and increased alkaline phosphatase activity and calcium levels were noted. In in vivo investigation, the PKH 26-labeled MSCs and composite systems were implanted in the distal femoral cavities of four rabbits. The local concentration of vancomycin was above the minimal inhibitory concentration for 56 days. Sample inhibition zone was 9 mm to 24 mm, and the relative activity was 11.8% to 100%. Implanted PKH 26-labeled MSCs were identified in the newly formed bony trabeculae in specimens at 2 and 4 months after implantation. The results offer a potential approach to meet clinical requirements in the treatment of infected bone defects.

The use of fluorescence-labeled mesenchymal stem cells in poly(lactide-co-glycolide)/hydroxyapatite/collagen hybrid graft as a bone substitute for posterolateral spinal fusion.

BACKGROUND: Posterolateral spinal fusion is used to treat patients with degenerative spinal disorders. In this study, we investigated the effectiveness of a mesenchymal stem cell (MSC)/hydroxyapatite/type I collagen hybrid graft for posterolateral spinal fusion in a rabbit model. METHODS: In vitro study, the hybrid graft was cultured in complete or osteogenic medium for 7 days and 14 days and examined by scanning electron microscopy. The alkaline phosphatase activity of the MSCs was assessed and the expression of osteogenic gene was determined by reverse transcription polymerase chain reaction. In vivo investigation, spinal fusion was examined using radiography, manual palpation, computed tomography, torsional loading tests, and histologic analysis. Furthermore, using a PKH fluorescence labeling system, we examined whether the newly formed bone was derived from the transplanted MSCs. RESULTS: Our data suggested that the MSCs differentiated into osteoblasts and produced extracellular matrix in the hybrid graft. Increased alkaline phosphatase activity was noted and mRNA of Cbfa-1 and osteopontin were detected. Radiographs and computed tomography images showed a continuous bone bridge and a satisfactory fusion mass incorporated into the transverse processes. The results of manual palpation and biomechanical data did not significantly differ between the two groups. Histologic examination of both groups revealed the presence of cartilage and endochondral ossification in the gaps between the grafted fragments. In situ tracing of the PKH 67-labeled MSCs indicated that the transplanted MSCs were partly responsible for the new bone formation. CONCLUSION: The hybrid graft could be effectively used to achieve posterolateral spinal fusion.

In vitro and in vivo investigation of drug-eluting implants for the treatment of periodontal disease.

This paper developed solvent-free drug-eluting implants for metronidazole delivery for the treatment of periodontal disease and investigated the characteristics of the drug's release from the implants, both in vitro and in vivo, using an HPLC assay. The metronidazole exhibited a two-stage release behavior in vitro with an initial burst release followed by a diffusion-controlled release and then a secondary burst release. The accumulated drug release reached 100% on the 18th day, and the drug-eluting implant was totally dissolved on the same day. Additionally, the drug-eluting disks were implanted within the sub-gingival space of both lower incisors of six rabbits. The curve of in vivo drug release was smoother and showed a predominantly diffusion-controlled release. The implants were totally dissolved at 2 weeks after implantation. The concentration of metronidazole remained above the MIC(90) during the entire investigation.

Role of Polymeric Local Drug Delivery in Multimodal Treatment of Malignant Glioma: A Review.

Malignant gliomas (MGs) are the most common and devastating primary brain tumor. At present, surgical interventions, radiotherapy, and chemotherapy are only marginally effective in prolonging the life expectancy of patients with MGs. Inherent heterogeneity, aggressive invasion and infiltration, intact physical barriers, and the numerous mechanisms underlying chemotherapy and radiotherapy resistance contribute to the poor prognosis for patients with MGs. Various studies have investigated methods to overcome these obstacles in MG treatment. In this review, we address difficulties in MG treatment and focus on promising polymeric local drug delivery systems. In contrast to most local delivery systems, which are directly implanted into the residual cavity after intratumoral injection or the surgical removal of a tumor, some rapidly developing and promising nanotechnological methods-including surface-decorated nanoparticles, magnetic nanoparticles, and focused ultrasound assist transport-are administered through (systemic) intravascular injection. We also discuss further synergistic and multimodal strategies for heightening therapeutic efficacy. Finally, we outline the challenges and therapeutic potential of these polymeric drug delivery systems.

Assessment of Antimicrobial Agents, Analgesics, and Epidermal Growth Factors-Embedded Anti-Adhesive Poly(Lactic-Co-Glycolic Acid) Nanofibrous Membranes: In vitro and in vivo Studies.

BACKGROUND: Postoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds. MATERIALS AND METHODS: Electrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes. RESULTS: The measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects. CONCLUSION: The outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.

Biodegradable Antimicrobial Agent/Analgesic/Bone Morphogenetic Protein-Loaded Nanofibrous Fixators for Bone Fracture Repair.

PURPOSE: Postoperative infection and pain management are of great concern to orthopedic surgeons. Although there are several protocols available to deal with these aspects, they are fraught with complications, such as cartilage damage, cardiovascular and neurological intoxication, and systemic adverse responses. Therefore, it is necessary to develop safe and effective perioperative protocols. In the current study, antimicrobial agents/analgesics/growth factor-embedded biodegradable hybrid fixators (polycaprolactone fixator + poly[lactide-co-glycolide] sheath-core structured nanofibers) for bone fracture repair were designed. METHODS: The biodegradable hybrid fixators were fabricated using solution-extrusion three-dimensional printing and electrospinning. In vitro, the characteristics of the hybrid fixators were examined. Additionally, the release of the incorporated vancomycin, ceftazidime, lidocaine, and bone morphogenetic protein-2 (BMP-2) was evaluated. The in vivo efficacy including drug-eluting properties, fracture repair, and pain management of the biomolecule-loaded nanofibrous fixators was investigated in rabbit rib-fracture models. RESULTS: The nanofibrous fixators released vancomycin, ceftazidime, and lidocaine in a sustained manner under both in vitro and in vivo conditions and protected BMP-2 from burst release. The implantation of these hybrid fixators around the fractured rib significantly improved animal activities and bone union, indicating that the inclusion of analgesic in the fixator effectively reduced postsurgical pain and thereby helped in recovery. CONCLUSION: The novel biomolecule-loaded nanofibrous hybrid fixators resulted in excellent therapeutic outcomes. These fixators may be effective in the repair of rib fractures in clinical settings and may help mitigate surgical complications, such as infection, nonunion, and intolerable postoperative pain.

Doxycycline-Embedded Nanofibrous Membranes Help Promote Healing of Tendon Rupture.

BACKGROUND: Despite recent advancements in surgical techniques, the repair of tendon rupture remains a challenge for surgeons. The purpose of this study was to develop novel doxycycline-loaded biodegradable nanofibrous membranes and evaluate their efficacy for the repair of Achilles tendon rupture in a rat model. MATERIALS AND METHODS: The drug-loaded nanofibers were prepared using the electrospinning process and drug release from the prepared membranes was investigated both in vitro and in vivo. Furthermore, the safety and efficacy of the drug-loaded nanofibrous membranes were evaluated in rats that underwent tendon surgeries. An animal behavior cage was employed to monitor the post-surgery activity of the animals. RESULTS: The experimental results demonstrated that poly(D,L-lactide-co-glycolide) (PLGA) nanofibers released effective concentrations of doxycycline for more than 40 days post-surgery, and the systemic plasma drug concentration was low. Rats receiving implantation of doxycycline-loaded nanofibers also showed greater activities and stronger tendons post-operation. CONCLUSION: Nanofibers loaded with doxycycline may have great potential in the repair of Achilles tendon rupture.

A Three-Dimensional Printed Polycaprolactone Scaffold Combined with Co-Axially Electrospun Vancomycin/Ceftazidime/Bone Morphological Protein-2 Sheath-Core Nanofibers for the Repair of Segmental Bone Defects During the Masquelet Procedure.

INTRODUCTION: Masquelet proposed a new solution for the healing of segmental bone defects, thus minimizing the disadvantages associated with traditional bone grafting. However, a major factor leading to the failure of this technique pertains to be the residual infection. Accordingly, we developed an antibiotic- and osteo-inductive agent-loaded composite scaffold to solve this problem. METHODS: A mesh-like polycaprolactone scaffold was prepared using a lab-exploited solution-type three-dimensional printer, and hybrid sheath-core structured poly(lactic-co-glycolic-acid) nanofibers were fabricated using co-axial electrospinning technology. Vancomycin, ceftazidime, and bone morphological protein (BMP)-2 were employed. The in vitro and in vivo (rabbit fracture model) release patterns of applied agents from the composite scaffold were investigated. RESULTS: The results revealed that the drug-eluting composite scaffold enabled the sustainable release of the medications for at least 30 days in vitro. Animal tests demonstrated that a high concentration of medications was maintained. Abundant growth factors were induced within the bioactive membrane stimulated by the applied scaffold. Finally, satisfactory bone healing potential was observed on radiological examination and biomechanical evaluation. DISCUSSION: The developed composite scaffold may facilitate bone healing by inducing bioactive membrane formation and yielding high concentrations of antibiotics and BMP-2 during the Masquelet procedure.

Preparation and in vitro/in vivo evaluation of doxorubicin-loaded poly[lactic-co-glycol acid] microspheres using electrospray method for sustained drug delivery and potential intratumoral injection.

For cancer treatment, intratumoral drug injection has many limitations and not commonly adopted. The poly[lactic-co-glycolic acid] (PLGA) has emerged as a promising vehicle to enhance the in vitro/in vivo characteristic of various drugs. We prepared doxorubicin-PLGA microspheres (DOX-PLGA MSs) using the electrospray method. An in vitro elution method was employed to evaluate the release of DOX from the MSs. We performed an in vivo study on rats, in which we directly injected DOX-PLGA MSs into the liver. We measured liver and plasma DOX concentrations to assess local retention and systemic exposure. The mean diameter of the MSs was 6.74 ±â€¯1.01 µm. The in vitro DOX release from the MSs exhibited a 12.3 % burst release on day 1, and 85.8 % of the drug had been released after 30 days. The in vivo tests revealed a higher local drug concentration at the target lobe of the liver than at the adjacent median lobe. In the first week, the DOX concentration in the peripheral blood of the MS group was lower than that of the direct DOX injection group. Based on the measured intrahepatic concentration and plasma pharmacokinetic profiles, DOX-PLGA MSs could be suitable vectors of chemotoxic agents for intratumoral injection.

Manufacture of dual-side surface-relief diffusers with various cross angles using ultrasonic embossing technique.

This paper reports a simple and effective ultrasonic embossing method which enables the rapid fabrication of dual-side surface-relief plastic diffusers with various cross angles. Metallic master molds bearing microstructures are fabricated using a tungsten carbide turning machine. A 1500-Watt ultrasonic vibrator with an output frequency of 20 kHz was used to replicate the microstructure onto 1 mm thick PMMA and PET films in the experiments. During ultrasonic embossing, the ultrasonic energy is converted into heat through intermolecular friction at the master mold/plastic plate interface due to asperities to melt the thermoplastic at the interface and thereby to replicate the microstructure. Under the proper processing conditions, high-performance dual-sided plastic diffusers of various cross-angles can be successfully fabricated. The proposed method shows great potential for fast fabrication of micro-optical components due to its simplicity and versatility.

Biodegradable andrographolide-eluting nanofibrous membranes for the treatment of cervical cancer.

BACKGROUND: In this study, we developed biodegradable andrographolide (AG)-eluting nanofibrous mats and evaluated their efficacy in treating cervical cancer. MATERIALS AND METHODS: Membranes of two different poly[(d,l)-lactide-co-glycolide] (PLGA)-to-AG ratios (6:1 and 3:1) were prepared via electrospinning technology. The liberation behavior of AG was evaluated. A cervical cancer model with C57BL/6J mice was created and employed for an in vivo efficacy assessment of the drug-eluting nanofibers. Twelve mice with cervical cancer were stochastically divided into three different groups (four animals per group): group A received no treatment as the control, group B was treated with pure PLGA mats, and group C was treated with AG-loaded nanofibrous membranes. The changes in tumor sizes were recorded. RESULTS: All membranes eluted high concentrations of AG at the target area for three weeks, while the systemic drug concentration in the blood remained low. Histological analysis showed no obvious tissue inflammation. Compared with the mice in groups A and B, the tumor size of the mice in group C decreased with time until day 25, when the daily drug concentration reduced to 3 µg/mL. CONCLUSION: Biodegradable nanofibers with a sustainable release of AG exhibit adequate efficacy and durability for the treatment of mice with cervical cancer.

Anesthetics and human epidermal growth factor incorporated into anti-adhesive nanofibers provide sustained pain relief and promote healing of surgical wounds.

Background: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique. Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films. Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2 weeks in vivo. In addition, rats implanted with the lidocaine/hEGF nanofibrous membranes exhibited greater activities than the control demonstrating the pain relief efficacy of the films. Conclusion: The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of lidocaine and hEGF offer post-operative pain relief and wound healing.

Extended pain relief achieved by analgesic-eluting biodegradable nanofibers in the Nuss procedure: in vitro and in vivo studies.

BACKGROUND: The most common complaint after the Nuss procedure is severe postoperative chest pain. The aim of this study was to evaluate the effectiveness of analgesic-eluting biodegradable nanofibers in pain relief after the Nuss procedure. MATERIALS AND METHODS: Poly(d,l)-lactide-co-glycolide, lidocaine, and ketorolac were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. This solution was electrospun into a nanofibrous membrane. The elution method and high-performance chromatography were used to characterize the in vitro drug release. Stainless steel bars with and without coating of the analgesic-eluting nanofibrous membrane were implanted underneath the sternums of New Zealand white rabbits. The in vivo characteristics were further investigated. RESULTS: The in vitro study showed that the biodegradable nanofibers released high doses of lidocaine and ketorolac within 10 days. The in vivo study demonstrated high local and systemic concentrations of lidocaine and ketorolac. The serum creatinine level was unaffected. Animals that received implants of the analgesic-eluting nanofiber-coated stainless steel bar exhibited significantly greater food and water ingestion and physical activity than the control group did, indicating effective pain relief. CONCLUSION: The proposed analgesic-eluting biodegradable nanofibers contribute to the achievement of extended pain relief after the Nuss procedure, without obvious adverse effects, in an animal model.