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Contraception Sep 2022To evaluate the relationship between time since contraceptive implant placement and retrieval outcomes in patients with implant migration into the pulmonary artery. (Review)
Review
OBJECTIVES
To evaluate the relationship between time since contraceptive implant placement and retrieval outcomes in patients with implant migration into the pulmonary artery.
STUDY DESIGN
We reviewed all cases of pulmonary artery implant migration referred to the Marie Lannelongue hospital from 2015 through 2020. Using our hospital database, we collected patients' clinical data and removal information to assess the success of therapeutic management according to the delay between implant insertion and removal.
RESULTS
We identified 8 cases. Physicians located 2 in the upper and 6 in the lower lobe. Five patients had associated pulmonary symptoms, most commonly, chest pain and dyspnea. Physicians attempted an endovascular procedure in all cases with successful removal in 3 patients. In the 5 failures, angiography displayed arterial thrombosis distal to the implant. These patients had successful removal with an open mini-thoracotomy (< 5 cm). None of the 8 patients had serious post-operative complications. For the 3 patients with successful endovascular retrieval, 2 had early diagnosis (≤ 3 months).
CONCLUSION
Endovascular approach with angiography should be performed as a first line treatment modality. Endothelialization and fibrosis within the vessel represent the principal limitations of endovascular strategy, but a retrieval could be attempted anyway with caution. In case of failure, an open approach is required.
IMPLICATIONS STATEMENT
When a migration into the pulmonary artery is diagnosed, health care professionals should refer patients as soon as possible to a tertiary center with a vascular surgery and/or interventional radiology and thoracic surgery departments.
Topics: Databases, Factual; Desogestrel; Drug Implants; Humans; Pulmonary Artery
PubMed: 35351447
DOI: 10.1016/j.contraception.2022.03.017 -
European Journal of Pharmaceutics and... Jun 2023Ozurdex is an FDA-approved sustained-release, biodegradable implant formulated to deliver the corticosteroid dexamethasone to the posterior segment of the eye for up to...
Ozurdex is an FDA-approved sustained-release, biodegradable implant formulated to deliver the corticosteroid dexamethasone to the posterior segment of the eye for up to 6 months. Hot-melt extrusion is used to prepare the 0.46 mm × 6 mm, rod-shaped implant by embedding the drug in a matrix of poly(lactic-co-glycolic acid) (PLGA) in a 60:40 drug:polymer ratio by weight. In our previous work, the Ozurdex implant was carefully studied and reverse engineered to produce a compositionally and structurally equivalent implant for further analysis. In this work, the reverse-engineered implant was thoroughly characterized throughout the in vitro dissolution process to elucidate the mechanisms of controlled drug release. The implant exhibited a triphasic release profile in 37 °C normal saline with a small burst release (1-2 %), a one-week lag phase with limited release (less than 10 %), and a final phase where the remainder of the dose was released over 3-4 weeks. The limited intermolecular interaction between dexamethasone and PLGA rendered the breakdown of the polymer the dominating mechanism of controlled release. A close relationship between drug release and total implant mass loss was observed. Unique chemical and structural differences were seen between the core of the implant and the implant surface driven by diffusional limitations, autocatalytic hydrolysis, and osmotic effects.
Topics: Polylactic Acid-Polyglycolic Acid Copolymer; Polyglycolic Acid; Lactic Acid; Drug Liberation; Dexamethasone; Drug Implants
PubMed: 37037387
DOI: 10.1016/j.ejpb.2023.04.003 -
Advanced Drug Delivery Reviews Dec 2020Long acting injectable formulations have been developed to sustain the action of drugs in the body over desired periods of time. These delivery platforms have been... (Review)
Review
Long acting injectable formulations have been developed to sustain the action of drugs in the body over desired periods of time. These delivery platforms have been utilized for both systemic and local drug delivery applications. This review gives an overview of long acting injectable systems that are currently in clinical use. These products are categorized in three different groups: biodegradable polymeric systems, including microparticles and implants; micro and nanocrystal suspensions and oil-based formulations. Furthermore, the applications of these drug delivery platforms for the management of various chronic diseases are summarized. Finally, this review addresses industrial challenges regarding the development of long acting injectable formulations.
Topics: Absorbable Implants; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Delivery Systems; Drug Implants; Drug Liberation; Emulsions; Humans; Microspheres; Nanoparticles; Polylactic Acid-Polyglycolic Acid Copolymer; Suspensions
PubMed: 33202261
DOI: 10.1016/j.addr.2020.11.008 -
International Journal of Pharmaceutics Mar 2021An extrusion-based 3D printer has been used for the manufacturing of sustained drug release poly(ε-caprolactone) (PCL) implants. Such implants can address issues of...
An extrusion-based 3D printer has been used for the manufacturing of sustained drug release poly(ε-caprolactone) (PCL) implants. Such implants can address issues of reduced patient compliance due to the necessary frequent administration of conventional drug delivery systems, such as tablets, capsules and solutions. The selected model drug for this study was lidocaine. Polycaprolactone core-shell implants, as well as polymeric implants with no barrier shell were printed with different drug loading, without the addition of solvents or further excipients. Scanning Electron Microscopy (SEM) analysis revealed the structural integrity of the printed formulations, while Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) were used to detect potential chemical interactions or modifications. Raman spectroscopy was also used to study material distribution in the prints. The drug release rate of the differently printed formulations was evaluated using a USP4 flow-through cell apparatus. All printed implants demonstrated sustained lidocaine release and the effectiveness of the PCL barrier in this regard. The Korsmeyer-Peppas model was suggested as the best fit to drug release profiles for all the produced implants. This work demonstrates that hot-melt extrusion-based 3D printing is a robust and promising technology for the production of personalisable drug-eluting implants.
Topics: Drug Implants; Drug Liberation; Excipients; Humans; Printing, Three-Dimensional; Tablets; Technology, Pharmaceutical; Ubiquitin-Specific Proteases
PubMed: 33540014
DOI: 10.1016/j.ijpharm.2021.120330 -
International Journal of Nanomedicine 2022Compared to intravenous administration, intratumoral drug administration enables the direct delivery of drugs to tumors and mitigates the systemic absorption of drugs...
INTRODUCTION
Compared to intravenous administration, intratumoral drug administration enables the direct delivery of drugs to tumors and mitigates the systemic absorption of drugs and associated drug-induced side effects. However, intratumoral drug administration presents several challenges. The high interstitial fluid pressure (IFP) of the tumor prevents the retention of drugs within the tumor; thus, significant amounts of the drugs are absorbed systemically through the bloodstream or delivered to non-target sites. To solve this problem, in this study, a drug-enclosed needle-type starch implant was developed that can overcome IFP and remain in the tumor.
METHODS
Injectable needle-type starch implants (NS implants) were prepared by starch gelatinization and drying. The structure, cytotoxicity, and anticancer effects of the NS implants were evaluated. Biodistribution of NS implants was evaluated in pork (in vitro), dissected liver (ex vivo), and 4T1 tumors in mice (in vivo) using a fluorescence imaging device.
RESULTS
The prepared NS implants exhibited a hydrogel structure after water absorption. NS implants showed effective cytotoxicity and anticancer effects by photothermal therapy (PTT). The NS implant itself has sufficient strength and can be easily injected into a desired area. In vivo, the NS implant continuously delivered drugs to the tumor more effectively and uniformly than conventional hydrogels and solutions.
CONCLUSION
This study demonstrated the advantages of needle-type implants. An injectable NS implant can be a new formulation that can effectively deliver drugs and exhibit anticancer effects.
Topics: Animals; Drug Implants; Hydrogels; Mice; Neoplasms; Starch; Tissue Distribution; Water
PubMed: 36147547
DOI: 10.2147/IJN.S370194 -
Contraception Aug 2020To assess etonogestrel contraceptive implant location and outcomes among women referred for "difficult" removal to a specialist clinic in South Africa. (Review)
Review
OBJECTIVES
To assess etonogestrel contraceptive implant location and outcomes among women referred for "difficult" removal to a specialist clinic in South Africa.
STUDY DESIGN
We performed a retrospective review of cases referred to our clinic for removal of nonpalpable, deep, migrated, or damaged implants, or failed removals from March to August 2017.
RESULTS
Most (n = 68, 92%) of the 74 referrals were nonpalpable in our clinic. We used ultrasound for localization and successfully removed 72 implants (97%) in the outpatient clinic.
CONCLUSION
With proper protocols and equipment, localization and removal of nonpalpable implants can be safely and effectively achieved in an outpatient African setting.
IMPLICATIONS
Access to providers specially trained in ultrasound localization should be available in all settings where implants are offered. Providing timely access to safe and effective implant removals in routine and difficult cases is essential to ensuring that implant programs are in alignment with rights-based, client-centered family planning principles.
Topics: Contraceptive Agents, Female; Desogestrel; Device Removal; Drug Implants; Female; Humans; Referral and Consultation; Retrospective Studies; South Africa
PubMed: 32339484
DOI: 10.1016/j.contraception.2020.04.013 -
Experimental Eye Research Nov 2020Elevated intraocular levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF) have been implicated the development of diabetic retinopathy. Over...
Elevated intraocular levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF) have been implicated the development of diabetic retinopathy. Over a decade of clinical evidence shows intravitreal injection of anti-VEGF agents is associated with decreased disease progression and preservation of vision. However, the treatment burden associated with monthly injections limits the effectiveness of existing anti-VEGF therapies. Current research has focused on sustained treatment paradigms such as longer acting drugs, drug delivery implants, and gene therapy. In this study, we tested a novel approach by dialyzing proteins from the vitreous using bioceramic implant composed of hydroxyapatite. Preliminary in vitro and in vivo studies demonstrate a high affinity and capacity for VEGF absorption. After three months implantation in New Zealand White Cross rabbits, the hydroxyapatite demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology. These studies demonstrate that prolonged VEGF suppression intraocularly may be accomplished with a bioceramic implant.
Topics: Angiogenesis Inhibitors; Animals; Biomarkers; Disease Models, Animal; Drug Implants; Durapatite; Glucocorticoids; Intravitreal Injections; Macular Edema; Rabbits; Vascular Endothelial Growth Factor A
PubMed: 32898514
DOI: 10.1016/j.exer.2020.108227 -
Contraception Nov 2021To determine the safety of etonogestrel contraceptive implant use among reproductive-age women who are solid organ transplant recipients.
OBJECTIVES
To determine the safety of etonogestrel contraceptive implant use among reproductive-age women who are solid organ transplant recipients.
STUDY DESIGN
We conducted a retrospective cohort study with matching of reproductive-age women (14-45 years) who were solid organ transplant recipients and received care at a tertiary medical center in Denver, Colorado between 2011 and 2019. We identified cases who used an etonogestrel contraceptive implant post-transplant and then matched controls (no hormonal contraceptive use) in a 1:1 ratio according to age, transplant type, and institution. We compared pregnancy patterns, post-transplant infections, immunosuppressant therapy adjustments, and graft complications between cases and controls. We also evaluated implant-related side effect profiles and continuation rates among cases only.
RESULTS
We identified 24 cases and 24 matched controls. When compared to age and transplant organ-matched controls, contraceptive implant users were not at increased risk for adverse transplant-related outcomes. Graft rejection was the most common transplant-related complication in both groups (n = 11, 45.8% cases; n = 10, 41.7% controls). Additionally, outcomes concerning pregnancies, infections and immunosuppressant therapy changes showed no statistically significant difference between either group.
CONCLUSIONS
This study provides the first data that the etonogestrel contraceptive implant is likely a safe contraceptive option for reproductive-age women who are solid organ transplant recipients. Given the solid organ transplant recommendations to avoid pregnancy during the first 1 to 2 years post-transplant, healthcare providers should continue to counsel solid organ transplant recipients at risk of pregnancy on the etonogestrel contraceptive implant as an effective and safe method of pregnancy prevention.
IMPLICATIONS
Reproductive age women who are solid organ transplant recipients face additional health risks with unintended pregnancies. The etonogestrel contraceptive implant remains a safe and effective method of contraception for this specific population, with no increase in graft-related complications among contraceptive implant users.
Topics: Adolescent; Adult; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Middle Aged; Organ Transplantation; Pregnancy; Retrospective Studies; Young Adult
PubMed: 34147509
DOI: 10.1016/j.contraception.2021.06.007 -
Drug Development and Industrial Pharmacy Oct 2021To provide a systematic map of the nature and extent of preclinical research concerning drug-releasing polymeric implants. (Review)
Review
PURPOSE
To provide a systematic map of the nature and extent of preclinical research concerning drug-releasing polymeric implants.
SIGNIFICANCE
By summarizing available data, this mapping review can guide the development of new drug-delivery devices.
METHODS
studies assessing drug-delivery implants were reviewed. A study protocol was registered at Open Science Framework. The association of polymers with prominent drugs, manufacturing processes, geometries, treatments, and anatomical locations was assessed using the VOSviewer software. The release periods were also evaluated.
RESULTS
A total of 423 articles, published between 1975 and 2020, were included and grouped into a framework with nine main categories. More than half of studies were published between 2010 and 2020. Among 201 individual polymers or combinations, the most investigated were PLGA, PCL, PLA, Silicone (SIL), EVA, and PU. Similarly, from 232 individual drugs or combinations, the most prominent were dexamethasone (DEX; anti-inflammatory), paclitaxel (PTX; anticancer), fluoruracil (anticancer), ciprofloxacin (CFX) hydrochloride (antibiotic), and gentamicin (GS; antibiotic). A total of 51 manufacturing processes were encountered, of which the most reported were solvent evaporation, compression molding (CM), extrusion (EX), electrospinning (ELS), and melt molding (MM). Among 38 implant geometries, cylinder (CIL) was the most prominent, followed by disk, square film, circular film (FCIR), and undefined film. Release times varied greatly, although the majority of articles ranged between 5 and 300 d.
CONCLUSIONS
Drug-delivery implants were highly heterogeneous due to its applicability for multiple health conditions. Most implants were made of PLGA and most drugs assessed presented anti-inflammatory, antibiotic, or anticancer effects. Solvent evaporation and CIL were the most prominent manufacturing process and geometry, respectively.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Ciprofloxacin; Cross-Sectional Studies; Drug Implants; Multimorbidity; Polymers; Research; Solvents
PubMed: 35171071
DOI: 10.1080/03639045.2022.2043354 -
Acta Biomaterialia Jul 2019Increased use of implantable biomedical devices demonstrates their potential in treating a wide variety of ailments and disorders in bone trauma and orthopaedic,... (Review)
Review
Increased use of implantable biomedical devices demonstrates their potential in treating a wide variety of ailments and disorders in bone trauma and orthopaedic, reconstructive, and craniofacial applications. However, the number of cases involving implant failure or malfunction due to bacterial infection have also increased in recent years. Implanted devices can facilitate the growth of bacteria as these micro-organisms have the potential to adhere to the implant and grow and develop to form biofilms. In an effort to better understand and mitigate these occurrences, biomaterials containing antimicrobial agents that can be released or presented within the local microenvironment have become an important area of research. In this review, we discuss critical factors that regulate antimicrobial therapy to sites of bone infection, such as key biomolecular considerations and platforms for delivery, as well as current in vivo models and current advances in the field. STATEMENT OF SIGNIFICANCE: This review outlines the important factors that are taken into consideration for the development of biomaterials for local delivery of therapeutics to the site of bone infections. An overview of important criteria for development of this model (such as type of bone defect, antimicrobial therapeutic, and delivery vehicle) are provided, along with current research that utilizes these considerations. Additionally, this review highlights recent clinical trials that have utilized antimicrobial therapeutics for treatment of osteomyelitis.
Topics: Animals; Anti-Infective Agents; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Biocompatible Materials; Biofilms; Bone Diseases, Infectious; Drug Implants; Humans
PubMed: 30654212
DOI: 10.1016/j.actbio.2019.01.015