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International Journal of Pharmaceutics May 2024In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis...
In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis treatment. The polymer is dissolved in a water-miscible solvent. The drug is dissolved or dispersed in this solution. Upon contact with aqueous body fluids, the solvent diffuses into the surrounding tissue and water penetrates into the formulation. Consequently, PLGA precipitates, trapping the drug. Often, N-methyl-2-pyrrolidine (NMP) is used as a water-miscible solvent. However, parenteral administration of NMP raises toxicity concerns. The aim of this study was to identify less toxic alternative solvent systems for in-situ forming PLGA implants. Various blends of polyethylene glycol 400 (PEG 400), triethyl citrate (TEC) and ethanol were used to prepare liquid formulations containing PLGA, ibuprofen (as an anti-inflammatory drug) and/or chlorhexidine dihydrochloride (as an antiseptic agent). Implant formation and drug release kinetics were monitored upon exposure to phosphate buffer pH 6.8 at 37 °C. Furthermore, the syringeability of the liquids, antimicrobial activity of the implants, and dynamic changes in the latter's wet mass and pH of the release medium were studied. Importantly, 85:10:5 and 60:30:10 PEG 400:TEC:ethanol blends provided good syringeability and allowed for rapid implant formation. The latter controlled ibuprofen and chlorhexidine release over several weeks and assured efficient antimicrobial activity. Interestingly, fundamental differences were observed concerning the underlying release mechanisms of the two drugs: Ibuprofen was dissolved in the solvent mixtures and partially leached out together with the solvents during implant formation, resulting in relatively pronounced burst effects. In contrast, chlorhexidine dihydrochloride was dispersed in the liquids in the form of tiny particles, which were effectively trapped by precipitating PLGA during implant formation, leading to initial lag-phases for drug release.
Topics: Polylactic Acid-Polyglycolic Acid Copolymer; Solvents; Ibuprofen; Drug Liberation; Polyethylene Glycols; Drug Implants; Polyglycolic Acid; Chlorhexidine; Lactic Acid; Citrates; Ethanol
PubMed: 38621617
DOI: 10.1016/j.ijpharm.2024.124121 -
Journal of Controlled Release :... Jan 2024Unmet medical needs in treating critical-size bone defects have led to the development of numerous innovative bone tissue engineering implants. Although additive... (Review)
Review
Unmet medical needs in treating critical-size bone defects have led to the development of numerous innovative bone tissue engineering implants. Although additive manufacturing allows flexible patient-specific treatments by modifying topological properties with various materials, the development of ideal bone implants that aid new tissue regeneration and reduce post-implantation bone disorders has been limited. Natural biomolecules are gaining the attention of the health industry due to their excellent safety profiles, providing equivalent or superior performances when compared to more expensive growth factors and synthetic drugs. Supplementing additive manufacturing with natural biomolecules enables the design of novel multifunctional bone implants that provide controlled biochemical delivery for bone tissue engineering applications. Controlled release of naturally derived biomolecules from a three-dimensional (3D) printed implant may improve implant-host tissue integration, new bone formation, bone healing, and blood vessel growth. The present review introduces us to the current progress and limitations of 3D printed bone implants with drug delivery capabilities, followed by an in-depth discussion on cutting-edge technologies for incorporating natural medicinal compounds embedded within the 3D printed scaffolds or on implant surfaces, highlighting their applications in several pre- and post-implantation bone-related disorders.
Topics: Humans; Bone Substitutes; Tissue Scaffolds; Printing, Three-Dimensional; Tissue Engineering; Bone and Bones; Bone Regeneration
PubMed: 37734674
DOI: 10.1016/j.jconrel.2023.09.025 -
Expert Opinion on Drug Delivery May 2024Retinal drug delivery has witnessed significant advancements in recent years, mainly driven by the prevalence of retinal diseases and the need for more efficient and... (Review)
Review
INTRODUCTION
Retinal drug delivery has witnessed significant advancements in recent years, mainly driven by the prevalence of retinal diseases and the need for more efficient and patient-friendly treatment strategies.
AREAS COVERED
Advancements in nanotechnology have introduced novel drug delivery platforms to improve bioavailability and provide controlled/targeted delivery to specific retinal layers. This review highlights various treatment options for retinal diseases. Additionally, diverse strategies aimed at enhancing delivery of small molecules and antibodies to the posterior segment such as implants, polymeric nanoparticles, liposomes, niosomes, microneedles, iontophoresis and mixed micelles were emphasized. A comprehensive overview of the special technologies currently under clinical trials or already in the clinic was provided.
EXPERT OPINION
Ideally, drug delivery system for treating retinal diseases should be less invasive in nature and exhibit sustained release up to several months. Though topical administration in the form of eye drops offers better patient compliance, its clinical utility is limited by nature of the drug. There is a wide range of delivery platforms available, however, it is not easy to modify any single platform to accommodate all types of drugs. Coordinated efforts between ophthalmologists and drug delivery scientists are necessary while developing therapeutic compounds, right from their inception.
Topics: Humans; Drug Delivery Systems; Retinal Diseases; Animals; Nanotechnology; Biological Availability; Ophthalmic Solutions; Administration, Ophthalmic; Pharmaceutical Preparations; Delayed-Action Preparations; Nanoparticles
PubMed: 38787783
DOI: 10.1080/17425247.2024.2358886 -
The Journal of Surgical Research Nov 2023Determine procedural outcomes and identify changing trends of utilization among patients undergoing histrelin implantation at a large pediatric tertiary care center over...
INTRODUCTION
Determine procedural outcomes and identify changing trends of utilization among patients undergoing histrelin implantation at a large pediatric tertiary care center over 15 y.
METHODS
Retrospective review of all patients undergoing histrelin implantation between January 2008 and April 2022.
RESULTS
A total of 746 patients underwent 1794 unique procedures (1364 placements/replacements, 430 removals). Procedures were performed in the clinic (1071, 60%), sedation unit (630, 35%), and operating room (93, 5%). A total of 14 (0.8%) complications were identified, including two patients that required early implant removal and one patient requiring antibiotics. Implants were placed for central precocious puberty (CPP, 579) or gender dysphoria (GD, 167). Cohort included 25.9% males and 74.1% females with mean age of implantation of 9.48 y (SD: 2.34, range: 1.05-17.34). The GD group is comprised of 52.4% males and 47.6% females, compared to 18.3% males and 81.7% females in the CPP. Significant difference was identified for mean age at placement by indication (CPP 8.65 y versus GD 12.34, P < 0.001). New patient referrals and implant procedures increased significantly over 14 y. Yearly frequency of patients receiving implants for CPP and GD increased significantly (P < 0.001), with proportion of GD patients increasing from 7% to 32%.
CONCLUSIONS
Histrelin procedures have increased in frequency overall with the greater increase noted in the GD cohort. The development of a streamlined process and a dedicated team have enabled histrelin procedures to be safely performed in the clinic setting for most, with a very low complication rate.
Topics: Male; Female; Humans; Child; Tertiary Care Centers; Drug Implants; Gonadotropin-Releasing Hormone; Puberty, Precocious; Retrospective Studies
PubMed: 37352739
DOI: 10.1016/j.jss.2023.05.019 -
Clinical Breast Cancer Oct 2023Postmastectomy radiotherapy (PMRT) on immediate breast reconstruction historically involved a marked increase in complication rate (up to 50%). Prepectoral breast...
BACKGROUND
Postmastectomy radiotherapy (PMRT) on immediate breast reconstruction historically involved a marked increase in complication rate (up to 50%). Prepectoral breast reconstruction (PPBR) has shown promising early postoperative results. This study aims to evaluate PPBR long-term results in PMRT setting.
MATERIALS AND METHODS
This is a retrospective monocentric analysis of 485 PPBR (439 patients) undergoing Acellular-Dermal-Matrix assisted direct-to-implant reconstruction (46 bilateral procedures) between January 2015 and December 2020 (mean FU:35.6 months). Group 1 comprised 401 PPBR not submitted to PMRT, and 84 reconstructions receiving PMRT in Group 2. Patients' characteristics, postoperative complication and revisional surgery rate were examined. PMRT characteristics and subcutaneous tissue thickness, measured in Group 2 by CT scan, were also evaluated.
RESULTS
Long-term complication rate was 11.2% in Group 1 vs. 21.4% in Group 2 (P-value = .019). Capsular contracture represented the only complication associated to a statistically significant difference between the 2 groups (P-value < .001). In Group 2, only 4.8% implant loss and 8.3% severe capsular contracture rate was found. In patients who underwent PMRT, 38.9% of complications settled with no consequences, and only 4.8% of patients needed revisional surgery in the long-term FU. According to multivariate analysis, drug intake and PMRT were significantly associated with postoperative complications. In Group 2, a thinner subcutaneous tissue was linked to a higher complication risk.
CONCLUSION
In our series, patients treated with PPBR who underwent PMRT, presented a low complication rate and minimal need for revisional surgery in the long-term follow-up, suggesting that this technique is feasible and safe also in PMRT context.
Topics: Humans; Female; Breast Neoplasms; Breast Implantation; Mastectomy; Retrospective Studies; Tissue Expansion Devices; Radiotherapy, Adjuvant; Mammaplasty; Breast Implants; Postoperative Complications; Contracture
PubMed: 37479666
DOI: 10.1016/j.clbc.2023.06.011 -
Retina (Philadelphia, Pa.) Aug 2023To assess the efficacy of a 0.18 mg intravitreal fluocinolone acetonide (FA) implant (Yutiq, EyePoint Pharmaceuticals, Watertown, MA) as a treatment option for patients...
PURPOSE
To assess the efficacy of a 0.18 mg intravitreal fluocinolone acetonide (FA) implant (Yutiq, EyePoint Pharmaceuticals, Watertown, MA) as a treatment option for patients with radiation retinopathy-related cystoid macular edema.
METHODS
A retrospective review of seven patients treated for uveal melanoma who developed radiation retinopathy-related cystoid macular edema. They were initially treated with intravitreal anti-vascular endothelial growth factor and/or steroid injections and then transitioned to intravitreal FA implant. Primary outcomes include best-corrected visual acuity, central subfield thickness, and number of additional injections.
RESULTS
After FA implant insertion, best-corrected visual acuity and central subfield thickness remained stable in all patients. The variance in best-corrected visual acuity decreased from 75.5 ETDRS letters (range 0-199 letters) to 29.8 (range 1.2-134) after FA implant insertion. Mean central subfield thickness was 384 µ m (range 165-641) and 354 µ m (range 282-493) before and after FA implant insertion, resulting in a 30- µ m mean reduction. The number of intravitreal injections (average 4.9, range 2-10) decreased after intravitreal FA implant insertion with only two patients requiring one additional FA implant (average 0.29, range 0-1) over a mean of 12.1 months (range 0.9-18.5) follow-up.
CONCLUSION
Intravitreal FA implant is an effective treatment for cystoid macular edema radiation retinopathy. The slow release of steroid allows for sustained control of macular edema, which correlated with stable visual acuity and decreased injection burden for patients.
Topics: Humans; Glucocorticoids; Macular Edema; Diabetic Retinopathy; Drug Implants; Fluocinolone Acetonide; Retrospective Studies; Intravitreal Injections
PubMed: 37027785
DOI: 10.1097/IAE.0000000000003808 -
Journal of Applied Oral Science :... 2024to evaluate the morphological and functional characteristics of the peri-implant bone tissue that was formed during the healing process by the placement implants using...
OBJECTIVES
to evaluate the morphological and functional characteristics of the peri-implant bone tissue that was formed during the healing process by the placement implants using two different surface treatments: hydrophilic Acqua™ (ACQ) and rough NeoPoros™ (NEO), in spontaneously hypertensive (SHR) and normotensive rats (Wistar) whether or not treated with losartan.
METHODOLOGY
In total, 96 male rats (48 Wistar and 48 SHR) were divided into eight subgroups: absolute control rough (COA NEO), absolute control hydrophilic (COA ACQ), losartan control rough (COL NEO), losartan control hydrophilic (COL ACQ), SHR absolute rough (SHR NEO), SHR absolute hydrophilic (SHR ACQ), SHR losartan rough (SHRL NEO), and SHR losartan hydrophilic (SHRL ACQ). The rats medicated with losartan received daily doses of the medication. NeoPoros™ and Acqua™ implants were installed in the tibiae of the rats. After 14 and 42 days of the surgery, the fluorochromes calcein and alizarin were injected in the rats. The animals were euthanized 67 days after treatment. The collected samples were analyzed by immunohistochemistry, biomechanics, microcomputerized tomography, and laser confocal scanning microscopy analysis.
RESULTS
The osteocalcin (OC) and vascular endothelium growth factor (VEGF) proteins had moderate expression in the SHRL ACQ subgroup. The same subgroup also had the highest implant removal torque. Regarding microarchitectural characteristics, a greater number of trabeculae was noted in the control animals that were treated with losartan. In the bone mineralization activity, it was observed that the Acqua™ surface triggered higher values of MAR (mineral apposition rate) in the COA, COL, and SHRL groups (p<0.05).
CONCLUSION
the two implant surface types showed similar responses regarding the characteristics of the peri-implant bone tissue, even though the ACQ surface seems to improve the early stages of osseointegration.
Topics: Animals; Losartan; Rats, Inbred SHR; Rats, Wistar; Male; Surface Properties; Dental Implants; Time Factors; X-Ray Microtomography; Reproducibility of Results; Immunohistochemistry; Hydrophobic and Hydrophilic Interactions; Osseointegration; Treatment Outcome; Dental Implantation, Endosseous; Microscopy, Confocal; Tibia; Analysis of Variance; Biomechanical Phenomena; Reference Values; Osteocalcin
PubMed: 38922240
DOI: 10.1590/1678-7757-2023-0374 -
Journal of Clinical Medicine Apr 2024This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related... (Review)
Review
This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related osteonecrosis of the jaw (MRONJ). A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of four key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the five predetermined criteria were chosen to enter the final review. A total of 445 implants in 135 subjects were included in the eight studies analyzed in the final review. The failure rate of dental implants after antiresorptive medication in the included studies was 23%, with 83% of failures attributed to MRONJ. The average time from antiresorptive drug initiation to MRONJ development was approximately 34 months, ranging from 3 months to 16 years. The majority of MRONJ cases were classified as stage 2, and all sites showed either complete healing or substantial mucosal coverage after treatment. This review highlights the significant impact of antiresorptive drugs on osseo- integrated implants, with MRONJ identified as a leading cause of implant failure. The potential role of peri-implantitis as a trigger for MRONJ is emphasized. Regular monitoring and maintaining good periodontal health, especially within the first three years of antiresorptive drug therapy initiation, are crucial for implant success. Physicians and dentists should provide comprehensive information to patients prescribed with antiresorptive drugs, emphasizing the need for an awareness of the risks of MRONJ in the context of osseointegrated implants. A longer term of follow-up is recommended to identify and manage MRONJ around dental implants in an early manner.
PubMed: 38610856
DOI: 10.3390/jcm13072091 -
The European Journal of Contraception &... Jun 2024Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent. (Review)
Review
INTRODUCTION
Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent.
PURPOSE
To document and characterise cases of etonogestrel contraceptive implant migration in the scientific literature.
METHODS
A systematic review of Medline, Embase and Global Health databases was carried out between January 2000 and January 2023 to identify articles presenting implant migrations. Narrative reviews, conference abstracts and articles not written in English or French were excluded.
RESULTS
Forty-five articles, mostly published since 2016, were identified (eight case series and 37 case reports), for a total of 148 independent cases of migration: in pulmonary blood vessels ( = 74), in non-pulmonary blood vessels ( = 16) and extravascular ( = 58). Many patients are asymptomatic and migration is often an incidental finding. A non-palpable implant and symptoms related to implant location (intra- or extra-vascular) may be indicative of migration. Inadequate insertion and normal or underweight appear to increase the risk of migration. Scientific societies and authors offer practical strategies to deal with implant migration.
CONCLUSION
Professionals who insert and remove contraceptive implants must be adequately trained. They need to be on the lookout for implant migration, and promptly refer patients to appropriate care if migration is suspected.
Topics: Humans; Desogestrel; Foreign-Body Migration; Female; Drug Implants; Contraceptive Agents, Female; Device Removal; Contraceptive Agents, Hormonal
PubMed: 38712717
DOI: 10.1080/13625187.2024.2342919 -
Military Medical Research May 2024Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental... (Review)
Review
Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.
Topics: Peri-Implantitis; Humans; Dental Implants; Biocompatible Materials; Biofilms; Surface Properties; Anti-Bacterial Agents
PubMed: 38741175
DOI: 10.1186/s40779-024-00532-9