Development of Chitosan and Polylactic Acid Based Methotrexate Intravitreal Micro-Implants to Treat Primary Intraocular Lymphoma: An In Vitro Study

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Soumyarwit Manna ◽  
James J. Augsburger ◽  
Zelia M. Correa ◽  
Julio A. Landero ◽  
Rupak K. Banerjee
Keyword(s):  
Drug Release ◽  
Polylactic Acid ◽  
Model Fit ◽  
External Beam Radiation ◽  
Intraocular Lymphoma ◽  
Therapeutic Window ◽  
Burst Release ◽  
Primary Intraocular Lymphoma ◽  
Beam Radiation ◽  
Micro Implants

Primary intraocular lymphoma (PIOL) is an uncommon but clinically and pathologically distinct form of non-Hodgkin's lymphoma. It provides a therapeutic challenge because of its diverse clinical presentations and variable clinical course. Currently available treatments for PIOL include intravenous multiple drug chemotherapy, external beam radiation therapy, and intravitreal methotrexate (MTX) injection. Each intravitreal injection of MTX is associated with potentially toxic peaks and subtherapeutic troughs of intraocular MTX concentration. Repetitive injections are required to maintain therapeutic levels of MTX in the eye. A sustained release drug delivery system is desired for optimized therapeutic release (0.2–2.0 μg/day) of MTX for over a period of 1 month to achieve effective treatment of PIOL. This study reports development of a unique intravitreal micro-implant, which administers therapeutic release of MTX over a period of 1 month. Chitosan (CS) and polylactic acid (PLA) based micro-implants are fabricated for different MTX loadings (10%, 25%, and 40% w/w). First, CS and MTX mixtures are prepared for different drug loadings, and lyophilized in Tygon® tubing to obtain CS-MTX fibers. The fibers are then cut into desired micro-implant lengths and dip coated in PLA for a hydrophobic surface coating. The micro-implant is characterized using optical microscopy, scanning electron microscopy (SEM), time of flight-secondary ion mass spectroscopy (ToF-SIMS), and differential scanning calorimetry (DSC) techniques. The release rate studies are carried out using a UV-visible spectrophotometer. The total release durations for 10%, 25%, and 40% w/w uncoated CS-MTX micro-implants are only 19, 29, and 32 h, respectively. However, the therapeutic release durations for 10%, 25%, and 40% w/w PLA coated CS-MTX micro-implants significantly improved to 58, 74, and 66 days, respectively. Thus, the PLA coated CS-MTX micro-implants are able to administer therapeutic release of MTX for more than 50 days. The release kinetics of MTX from the coated micro-implants is explained by (a) the Korsmeyer–Peppas and zero order model fit (R2 ∼ 0.9) of the first 60% of the drug release, which indicates the swelling of polymer and initial burst release of the drug; and (b) the first order and Higuchi model fit (R2 ∼ 0.9) from the tenth day to the end of drug release, implying MTX release in the therapeutic window depends on its concentration and follows diffusion kinetics. The PLA coated CS-MTX micro-implants are able to administer therapeutic release of MTX for a period of more than 1 month. The proposed methodology could be used for improved treatment of PIOL.

Influence of Hydrophobic Surface Modification of Chitosan Based Methotrexate (MTX) Micro Implants to Treat Intraocular Lymphoma

2013 ◽  
Author(s):  
Soumyarwit Manna ◽  
James J. Augsburger ◽  
Zelia M. Correa ◽  
Julio A. Landero ◽  
Rupak K. Banerjee
Keyword(s):  
Surface Modification ◽  
Sustained Release ◽  
Hydrophobic Surface ◽  
Intraocular Lymphoma ◽  
Therapeutic Dosage ◽  
Primary Intraocular Lymphoma ◽  
Rare Form ◽  
Chemotherapeutic Effect ◽  
Oncology Practice ◽  
Micro Implants

Primary intraocular lymphoma (PIOL) is a rare form of lymphoma which is encountered in ocular oncology practice. Most preferred treatment has been intravitreal MTX injections which do not have a long lasting chemotherapeutic effect due to rapid elimination of the drug. In this study, chitosan (CS) and polylactic acid (PLA) based intraocular implants are fabricated for different MTX loadings (10%, 25% and 40% w/w). The implants administer a therapeutic dosage of 0.2–2.0 μg/day of MTX over a period of a month. PLA coated CS-MTX implants can be used for sustained release of MTX, thereby improving the treatment of PIOL.

Doxorubicin release from optimized electrospun polylactic acid nanofibers

2016 ◽  
Vol 47 (1) ◽  
pp. 71-88 ◽  
Author(s):  
Amir Doustgani
Keyword(s):  
Differential Scanning Calorimetry ◽  
Drug Release ◽  
Polylactic Acid ◽  
Fiber Diameter ◽  
Experimental Result ◽  
Coefficient Of Determination ◽  
Release Mechanism ◽  
Burst Release ◽  
Fiber Morphology ◽  
Scanning Calorimetry

Electrospinning has been known as an efficient method for fabrication of polymer nanofibers. In this study, an electrospun nanofibrous mats based on polylactic acid with a defined release using doxorubicin was developed. The effects of process parameters, such as concentration, distance, applied voltage, temperature and flow rate on the mean diameter of electrospun doxorubicin-loaded polylactic acid nanofibers were investigated. The fiber morphology and mean fiber diameter of prepared nanofibers were investigated by scanning electron microscopy. Differential scanning calorimetry was employed to identify the presence of doxorubicin within nanofibers. Response surface methodology based on a five-level, five-variable central composite design was used to model the average diameter of electrospun polylactic acid/doxorubicin nanofibers. Mean fiber diameter was correlated to these variables by using a polynomial function at a 95% confidence level. The coefficient of determination of the model was found to be 0.93. The predicted fiber diameter was in good agreement with the experimental result. Differential scanning calorimetry results showed that the doxorubicin was loaded into the nanofibers successfully. In vitro drug release in phosphate-buffered solution and acetate buffer for the optimized and non-optimized samples demonstrated that diffusion is the dominant drug release mechanism for drug-loaded fibers. The initial burst release was observed for non-optimized nanofibers compared to optimized nanofibers. Optimized drug-loaded polylactic acid nanofibers could be good candidates for biomedical applications.

1141: A Randomized Controlled Trial Comparing External Beam Radiation and Cryoablation in Localized Prostate Cancer

2007 ◽  
Vol 177 (4S) ◽  
pp. 376-377 ◽  
Author(s):  
Bryan J. Donnelly ◽  
John C. Saliken ◽  
Penny Brasher ◽  
Scott Ernst ◽  
Harold Lau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Localized Prostate Cancer ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation ◽  
Randomized Controlled

Spinal laser interstitial thermal therapy: single-center experience and outcomes in the first 120 cases

2020 ◽  
pp. 1-10
Author(s):  
Dhiego C. A. Bastos ◽  
Rafael A. Vega ◽  
Jeffrey I. Traylor ◽  
Amol J. Ghia ◽  
Jing Li ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Local Control ◽  
Thoracic Spine ◽  
Adjuvant Radiotherapy ◽  
Neurological Complications ◽  
Thermal Therapy ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Laser Interstitial Thermal Therapy ◽  
Hazard Ratios

OBJECTIVEThe objective of this study was to present the results of a consecutive series of 120 cases treated with spinal laser interstitial thermal therapy (sLITT) to manage epidural spinal cord compression (ESCC) from metastatic tumors.METHODSThe electronic records of patients treated from 2013 to 2019 were analyzed retrospectively. Data collected included demographic, pathology, clinical, operative, and imaging findings; degree of epidural compression before and after sLITT; length of hospital stay; complications; and duration before subsequent oncological treatment. Independent-sample t-tests were used to compare means between pre- and post-sLITT treatments. Survival was estimated by the Kaplan-Meier method. Multivariate logistic regression was used to analyze predictive factors for local recurrence and neurological complications.RESULTSThere were 110 patients who underwent 120 sLITT procedures. Spinal levels treated included 5 cervical, 8 lumbar, and 107 thoracic. The pre-sLITT Frankel grades were E (91.7%), D (6.7%), and C (1.7%). The preoperative ESCC grade was 1c or higher in 92% of cases. Metastases were most common from renal cell carcinoma (39%), followed by non–small cell lung carcinoma (10.8%) and other tumors (35%). The most common location of ESCC was in the vertebral body (88.3%), followed by paraspinal/foraminal (7.5%) and posterior elements (4.2%). Adjuvant radiotherapy (spinal stereotactic radiosurgery or conventional external beam radiation therapy) was performed in 87 cases (72.5%), whereas 33 procedures (27.5%) were performed as salvage after radiotherapy options were exhausted. sLITT was performed without need for spinal stabilization in 87 cases (72.5%). Post-sLITT Frankel grades were E (85%), D (10%), C (4.2%), and B (0.8%); treatment was associated with a median decrease of 2 ESCC grades. The local control rate at 1 year was 81.7%. Local control failure occurred in 25 cases (20.8%). The median progression-free survival was not reached, and overall survival was 14 months. Tumor location in the paraspinal region and salvage treatment were independent predictors of local recurrence, with hazard ratios of 6.3 and 3.3, respectively (p = 0.01). Complications were observed in 22 cases (18.3%). sLITT procedures performed in the lumbar and cervical spine had hazard ratios for neurological complications of 15.4 and 17.1 (p < 0.01), respectively, relative to the thoracic spine.CONCLUSIONSsLITT is safe and provides effective local control for high-grade ESCC from vertebral metastases in the thoracic spine, particularly when combined with adjuvant radiotherapy. The authors propose considering sLITT as an alternative to open surgery in selected patients with spinal metastases.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 37-41 ◽  
Author(s):  
William F. Regine ◽  
Roy A. Patchell ◽  
James M. Strottmann ◽  
Ali Meigooni ◽  
Michael Sanders ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Content Type ◽  
Group B ◽  
Fine Print

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.

Diode in Vivo Dosimetry for Patients Receiving External Beam Radiation Therapy

10.37206/88 ◽  
2005 ◽  
Author(s):  
Ellen Yorke ◽  
Rodica Alecu ◽  
Li Ding ◽  
Doracy Fontenla ◽  
Andre Kalend ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
External Beam Radiation Therapy ◽  
External Beam Radiation ◽  
In Vivo Dosimetry ◽  
External Beam ◽  
Beam Radiation
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