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Drug Delivery Nov 2018Along with the development of nanotechnological strategies for biomaterials associated with the prevention of infections, a myriad of clinically unproven techniques have... (Review)
Review
Along with the development of nanotechnological strategies for biomaterials associated with the prevention of infections, a myriad of clinically unproven techniques have been described to date. In this work, the aim was to perform a critical analysis of the literature available concerning antibacterial biomaterials for oral implantology and to provide a practical derivation for such a purpose. As anti-adhesive strategies may affect osseointegration, they should no longer be recommended for inclusion in this class of biomaterials, despite promising results in biomedical engineering for other, non-bone load bearing organs. Targeted, antibacterial drug delivery is most likely desirable in the case of intraosseous implants. Interfering factors such as the oral cavity environment, saliva, the bacterial microbiome, as well as, the characteristics of the alveolar mucosa and peri-implant space must be taken into account when calculating the local pharmacokinetics for antibacterial coatings. Effective release is crucial for tailoring antibacterial implant longevity providing minimal inhibitory concentration (MIC) for the desired amount of time, which for oral implants, should be at least the cumulative time for the osseointegration period and functional loading period within the tissues. These parameters may differ between the implant type and its anatomical site. Also, the functional drug concentration in the peri-implant space should be calculated as the amount of the drug released from the implant surface including the concentration of the drug inactivated by biological fluids of the peri-implant space or saliva flow throughout the effective release time.
Topics: Alveolar Bone Loss; Anti-Bacterial Agents; Biocompatible Materials; Drug Delivery Systems; Drug Implants; Humans; Maxillofacial Prosthesis Implantation; Microbial Sensitivity Tests; Mouth; Osseointegration
PubMed: 29968496
DOI: 10.1080/10717544.2018.1477855 -
International Journal of Nanomedicine 2017To address the limitations of traditional drug delivery, TiO nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to... (Review)
Review
To address the limitations of traditional drug delivery, TiO nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future.
Topics: Animals; Coated Materials, Biocompatible; Drug Delivery Systems; Drug Implants; Electrochemistry; Electrodes; Humans; Hydrogen-Ion Concentration; Magnetics; Micelles; Nanotubes; Neoplasms; Polymers; Titanium; Ultrasonics
PubMed: 28053530
DOI: 10.2147/IJN.S117498 -
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 -
Endocrine Development 2016The histrelin implant has emerged as a therapeutic option for the treatment of central precocious puberty that has been favorably received by patients and providers.... (Review)
Review
The histrelin implant has emerged as a therapeutic option for the treatment of central precocious puberty that has been favorably received by patients and providers. Inserted subcutaneously, the 50-mg implant provides continuous release of the potent gonadotropin-releasing hormone analog (GnRHa) histrelin. Profound suppression of the hypothalamic-pituitary-gonadal (HPG) axis occurs within 1 month of its placement resulting in pubertal arrest, attenuation of skeletal advancement and a progressive increase in predicted adult height. Although marketed for annual use, suppression lasting 2 years from a single implant has been demonstrated. Placing and removing the device is a minor outpatient procedure easily accomplished by a pediatric surgeon using local anesthesia. The major downside to the implant is a ∼25% rate of breakage upon removal. Information about the recovery of the HPG axis following histrelin explantation is limited but suggests an average time to menarche comparable with depot GnRHa formulations albeit with wide individual variation.
Topics: Child; Drug Implants; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious
PubMed: 26683629
DOI: 10.1159/000439330 -
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 -
Journal of Acquired Immune Deficiency... Jul 2021Long-acting pre-exposure prophylaxis (LA-PrEP) formulated as implants and injections are promising prevention method strategies offering simplicity, discretion, and long...
BACKGROUND
Long-acting pre-exposure prophylaxis (LA-PrEP) formulated as implants and injections are promising prevention method strategies offering simplicity, discretion, and long dose duration. Men are important end users of LA-PrEP, and early assessment of their preferences could enhance downstream male engagement in HIV prevention.
METHODS
A discrete-choice experiment survey was conducted with 406 men, aged 18-24, in Cape Town, South Africa, to assess preferences for 5 LA-PrEP attributes with 2-4 pictorially-depicted levels: delivery form, duration, insertion location, soreness, and delivery facility. Latent class analysis was used to explore heterogeneity of preferences and estimate preference shares.
RESULTS
The median age was 21 (interquartile range 19-22), and 47% were men who have sex with men. Duration was the most important product attribute. Latent class analysis identified 3 classes: "duration-dominant decision makers" (46%) were the largest class, defined by significant preference for a longer duration product. "Comprehensive decision makers" (36%) had preferences shaped equally by multiple attributes and preferred implants. "Injection-dominant decision makers" (18%) had strong preference for injections (vs. implant) and were significantly more likely to be men who have sex with men. When estimating shares for a 2-month injection in the buttocks with mild soreness (HPTN regimen) vs. a 6-month implant (to arm) with moderate soreness (current target), 95% of "injection-dominant decision makers" would choose injections, whereas 79% and 63% of "duration-dominant decision makers" and "comprehensive decision makers" would choose implant.
CONCLUSIONS
Young South African men indicated acceptability for LA-PrEP. Preferences were shaped mainly by duration, suggesting a sizeable market for implants, and underscoring the importance of product choice. Further research into men's acceptability of LA PrEP strategies to achieve engagement in these HIV prevention tools constitutes a priority.
Topics: Adolescent; Anti-HIV Agents; Data Collection; Delayed-Action Preparations; Drug Implants; HIV Infections; HIV-1; Humans; Male; Patient Preference; South Africa; Young Adult
PubMed: 33633031
DOI: 10.1097/QAI.0000000000002670 -
Drug Delivery Dec 2022The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based...
The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly(d,l-lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the and release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.
Topics: Animals; Animals, Outbred Strains; Antibiotics, Antineoplastic; Bone Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Implants; Drug Liberation; Female; Male; Mice; Mice, Inbred BALB C; Osteosarcoma; Polyethylene Glycols; Polylactic Acid-Polyglycolic Acid Copolymer; Random Allocation; Rats, Sprague-Dawley; Technology, Pharmaceutical; Xenograft Model Antitumor Assays; Rats
PubMed: 35147071
DOI: 10.1080/10717544.2022.2032878 -
Acta Biomaterialia Apr 2019Macroscale biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with anti-cancer immunotherapies.... (Review)
Review
Macroscale biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with anti-cancer immunotherapies. Immunotherapies on their own typically have poor delivery properties, and often require repeated high-dose injections that result in serious off-tumor effects and/or limited efficacy. Rationally designed biomaterials allow for discrete localization and controlled release of immunotherapeutic agents, and have been shown in a large number of applications to improve outcomes in the treatment of cancers via immunotherapy. Among various strategies, macroscale biomaterial delivery systems can take the form of robust tablet-like scaffolds that are surgically implanted into a tumor resection site, releasing programmed immune cells or immunoregulatory agents. Alternatively they can be developed as soft gel-like materials that are injected into solid tumors or sites of resection to stimulate a potent anti-tumor immune response. Biomaterials synthesized from diverse components such as polymers and peptides can be combined with any immunotherapy in the modern toolbox, from checkpoint inhibitors and stimulatory adjuvants, to cancer antigens and adoptive T cells, resulting in unique synergies and improved therapeutic efficacy. The field is growing rapidly in size as publications continue to appear in the literature, and biomaterial-based immunotherapies are entering clinical trials and human patients. It is unarguably an exciting time for cancer immunotherapy and biomaterial researchers, and further work seeks to understand the most critical design considerations in the development of the next-generation of immunotherapeutic biomaterials. This review will discuss recent advances in the delivery of immunotherapies from localized biomaterials, focusing on macroscale implantable and injectable systems. STATEMENT OF SIGNIFICANCE: Anti-cancer immunotherapies have shown exciting clinical results in the past few decades, yet they suffer from a few distinct limitations, such as poor delivery kinetics, narrow patient response profiles, and systemic side effects. Biomaterial systems are now being developed that can overcome many of these problems, allowing for localized adjuvant delivery, focused dose concentrations, and extended therapy presentation. The field of biocompatible carrier materials is uniquely suited to be combined with immunotherapy, promising to yield significant improvements in treatment outcomes and clinical care. In this review, the first pioneering efforts and most recent advances in biomaterials for immunotherapeutic applications are explored, with a specific focus on implantable and injectable biomaterials such as porous scaffolds, cryogels, and hydrogels.
Topics: Biocompatible Materials; Drug Implants; Humans; Hydrogels; Immunologic Factors; Immunotherapy; Neoplasms
PubMed: 30771535
DOI: 10.1016/j.actbio.2019.02.016 -
European Journal of Pharmaceutics and... Aug 2022The aim of this study was to better understand the importance of the diameter of poly(lactic-co-glycolic acid) (PLGA)-based implants on system performance, in particular...
The aim of this study was to better understand the importance of the diameter of poly(lactic-co-glycolic acid) (PLGA)-based implants on system performance, in particular the control of drug release. Different types of ibuprofen-loaded implants were prepared by hot melt extrusion using a Leistritz Nano 16 twin-screw extruder. Drug release was measured in well agitated phosphate buffer pH7.4 bulk fluid and in agarose gels in Eppendorf tubes or transwell plates. Dynamic changes in the implants' dry & wet mass, volume, polymer molecular weight as well as inner & outer morphology were monitored using gravimetric analysis, optical macroscopy, gel permeation chromatography and scanning electron microscopy. The physical states of the drug and polymer were determined by DSC. Also pH changes in the release medium were investigated. Irrespective of the type of experimental set-up, the resulting absolute and relative drug release rates decreased with increasing implant diameter (0.7-2.8 mm). Bi-phasic drug release was observed in all cases from the monolithic solutions (ibuprofen was dissolved in the polymer): A zero order release phase was followed by a final, rapid drug release phase (accounting for 80-90% of the total drug dose). The decrease in the relative drug release rate with increasing system diameter can be explained by the increase in the diffusion pathway lengths to be overcome. Interestingly, also the onset of the final rapid drug release phase was delayed with increasing implant diameter. This can probably be attributed to the higher mechanical stability of thicker devices, offering more resistance to substantial entire system swelling.
Topics: Drug Implants; Drug Liberation; Ibuprofen; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers
PubMed: 35659920
DOI: 10.1016/j.ejpb.2022.05.020 -
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