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Medecine Sciences : M/S Jan 2017Implants for controlled drug delivery can be very helpful to improve the therapeutic efficacy of a medical treatment, and at the same time reduce the risk of toxic side... (Review)
Review
Implants for controlled drug delivery can be very helpful to improve the therapeutic efficacy of a medical treatment, and at the same time reduce the risk of toxic side effects. In this article, four different strategies are exemplarily presented: hybrid bone substitutes combining hydroxyapatite and chitosan hydrogels; vascular stents coated with a bio-inspired polymer; cochlear implants for local dexamethasone delivery; and in-situ forming implants for periodontitis treatment. But this is only a restricted selection, and numerous other approaches and applications based on implants releasing a drug (or a combination of drugs) exist. Compared to conventional implants or pharmaceutical dosage forms, they might offer decisive advantages.
Topics: Animals; Cochlear Implants; Dental Implants; Drug Delivery Systems; Drug Implants; Drug-Eluting Stents; Graft Occlusion, Vascular; Humans; Periodontium; Polymers
PubMed: 28120753
DOI: 10.1051/medsci/20173301006 -
Emerging Topics in Life Sciences Dec 2020Implants have long been used in the field of drug delivery as controlled release vehicles and are now being investigated as single-shot vaccine technologies. Implants... (Review)
Review
Implants have long been used in the field of drug delivery as controlled release vehicles and are now being investigated as single-shot vaccine technologies. Implants have shown great promise, minimizing the need for multiple immunizations while stimulating potent immune responses with reduced doses of vaccine. Synchronous release of vaccine components from implants over an appropriate period of time is important in order to avoid issues including immune tolerance, sequestration or deletion. Traditionally, implants require surgical implantation and removal, which can be a barrier to their widespread use. Degradable and in situ implants are now being developed that can be administered using minimally invasive subcutaneous or intramuscular injection techniques. Injectable hydrogels remain the most commonly studied approach for sustained vaccine delivery due to their ease of administration and tunable degradation properties. Despite exciting advancements in the field of vaccine implants, few technologies have progressed to clinical trials. To increase the likelihood of clinical translation of vaccine implants, strategic testing of disease-relevant antigens in appropriate species is essential. In this review, the significance of vaccine implants and the different types of implants being developed to deliver vaccines are discussed.
Topics: Antigens; Drug Delivery Systems; Drug Implants; Hydrogels; Immunization; Vaccines
PubMed: 33231265
DOI: 10.1042/ETLS20200164 -
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 -
Current Drug Targets 2021Oral route of administration is widely accepted and desired because of its versatility, convenience, and, most importantly, patient compliance. Multiparticulate systems... (Review)
Review
Oral route of administration is widely accepted and desired because of its versatility, convenience, and, most importantly, patient compliance. Multiparticulate systems like granules and pellets are more advantageous when compared to single-unit dosage forms, as they are capable of distributing the drug more evenly in the gastrointestinal tract. The current paper focuses on pellets, the merits and demerits associated, various pelletization techniques, and their characterization. It also focuses on how pellets can be employed for drug delivery is controlled and sustained release formulations. It gives a complete emphasis on the drug and excipients that can be used in pellet formation, the marketed formulations, and the research pertaining to pellets.
Topics: Administration, Oral; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Drug Implants; Excipients; Humans; Solubility
PubMed: 33475056
DOI: 10.2174/1389450122999210120204248 -
Expert Opinion on Drug Delivery May 2021: Drug eluting implants offer patient convenience and improved compliance through less frequent dosing, eliminating repeated, painful injections and providing localized,... (Review)
Review
: Drug eluting implants offer patient convenience and improved compliance through less frequent dosing, eliminating repeated, painful injections and providing localized, site specific delivery with applications in contraception, ophthalmology, and oncology.: This review provides an overview of available implant products, design approaches, biodegradable and non-biodegradable polymeric materials, and fabrication techniques with a focus on commercial applications and industrial drug product development. Developing trends in the field, including expanded availability of suitable excipients, development of novel materials, scaled down manufacturing process, and a wider understanding of the implant development process are discussed and point to opportunities for differentiated drug eluting implant products.: In the future, long-acting implants will be important clinical tools for prophylaxis and treatment of global health challenges, especially for infectious diseases, to reduce the cost and difficulty of treating chronic indications, and to prolong local delivery in difficult to administer parts of the body. These products will help improve patient safety, adherence, and comfort.
Topics: Drug Delivery Systems; Drug Development; Drug Implants; Excipients; Humans; Pharmaceutical Preparations
PubMed: 33275066
DOI: 10.1080/17425247.2021.1856072 -
Current Drug Targets 2015Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such... (Review)
Review
Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant- body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS.
Topics: Animals; Diagnostic Imaging; Drug Delivery Systems; Drug Implants; Humans; Magnetic Resonance Imaging; Optical Imaging; Tomography, X-Ray Computed; Ultrasonography
PubMed: 25418857
DOI: 10.2174/1389450115666141122211920 -
Reproductive Biology and Endocrinology... Mar 2021Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress...
BACKGROUND
Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use.
METHODS
Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30μg/d, medium-0.17μg/d, low-0.09μg/d, placebo-0.00μg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA.
RESULTS
Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation.
CONCLUSION
Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.
Topics: Animals; Contraceptive Agents, Female; Desogestrel; Dose-Response Relationship, Drug; Drug Implants; Estrus; Female; Humans; Models, Animal; Progestins; Rats; Rats, Sprague-Dawley; Rodentia
PubMed: 33752672
DOI: 10.1186/s12958-021-00729-w -
Promising Approach in the Treatment of Glaucoma Using Nanotechnology and Nanomedicine-Based Systems.Molecules (Basel, Switzerland) Oct 2019Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting... (Review)
Review
Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye's peculiar and exclusive anatomy and physiology continue to pose a significant obstacle to researchers and pharmacologists in the provision of efficient drug delivery. Though several traditional invasive and noninvasive eye therapies exist, including implants, eye drops, and injections, there are still significant complications that arise which may either be their low bioavailability or the grave ocular adverse effects experienced thereafter. On the other hand, new nanoscience technology and nanotechnology serve as a novel approach in ocular disease treatment. In order to interact specifically with ocular tissues and overcome ocular challenges, numerous active molecules have been modified to react with nanocarriers. In the general population of glaucoma patients, disease growth and advancement cannot be contained by decreasing intraocular pressure (IOP), hence a spiking in future research for novel drug delivery systems and target therapeutics. This review focuses on nanotechnology and its therapeutic and diagnostic prospects in ophthalmology, specifically glaucoma. Nanotechnology and nanomedicine history, the human eye anatomy, research frontiers in nanomedicine and nanotechnology, its imaging modal quality, diagnostic and surgical approach, and its possible application in glaucoma will all be further explored below. Particular focus will be on the efficiency and safety of this new therapy and its advances.
Topics: Animals; Biological Availability; Drug Delivery Systems; Drug Implants; Drug Liberation; Glaucoma; Humans; Intraocular Pressure; Mice; Nanomedicine; Rabbits; Tomography, Optical Coherence; Trabecular Meshwork
PubMed: 31652593
DOI: 10.3390/molecules24203805 -
Daru : Journal of Faculty of Pharmacy,... Dec 2020Liqui-Pellet is potentially an emerging next-generation oral pill, which has shown promising results with unique advantages as well as displaying potential for...
AIM
Liqui-Pellet is potentially an emerging next-generation oral pill, which has shown promising results with unique advantages as well as displaying potential for commercial feasibility. Since Liqui-Pellet technology is still in its infancy, it is important to explore the parameters that can affect its performance, particularly the drug release rate. Therefore, the aim of this study is to investigate thoroughly the effect of Avicel PH101 (carrier) and Aerosil 300 (coating material) ratio (R-value) in Liqui-Pellet.
METHODS
Key parameter for Liqui-Pellet formulation in this study was the ratio of carrier and coating material. Tests were carried out to assess the physicochemical properties of different formulations. This involved looking into particle size, robustness, flowability, solid-state and drug release profile. The morphology of Liqui-Pellet was investigated by SEM.
RESULTS
It is found that R-value does not have a major effect on the success of Liqui-Pellet production. However, R-value does seem to have an effect on Liqui-Pellet size at a certain water content level and a slight effect on the drug release rate. A decrease in Avicel PH101 concentration and an increase in Aerosil 300 concentration in Liqui-Pellet formulations can reduce Liqui-Pellet size and slightly increase drug release rate by 9% after 2 h. The data shows Liqui-Pellet is resistant to friability, able to achieve exceptional flow property and have smooth surfaces, which is critical for applying coatings technology. Such properties are ideal in terms of commercial manufacturing. The XRPD and DSC both show the reduction in formulation crystallinity, which is expected in Liqui-Pellet formulation as a result of solubility of the drug in the co-solvent used in the preparation of Liqui-Pellets.
CONCLUSION
Overall it seems that R-value can affect Liqui-Pellet drug release rate and size but not on the production success rate.
Topics: Calorimetry, Differential Scanning; Cellulose; Drug Compounding; Drug Implants; Microscopy, Electron, Scanning; Naproxen; Particle Size; Powder Diffraction; Silicon Dioxide; Solubility; X-Ray Diffraction
PubMed: 32757155
DOI: 10.1007/s40199-020-00362-9 -
Advanced Materials (Deerfield Beach,... Jun 2024In recent years, tremendous effort is devoted to developing platforms, such as implantable drug delivery systems (IDDSs), with temporally and spatially controlled drug... (Review)
Review
In recent years, tremendous effort is devoted to developing platforms, such as implantable drug delivery systems (IDDSs), with temporally and spatially controlled drug release capabilities and improved adherence. IDDSs have multiple advantages: i) the timing and location of drug delivery can be controlled by patients using specific stimuli (light, sound, electricity, magnetism, etc.). Some intelligent "closed-loop" IDDS can even realize self-management without human participation. ii) IDDSs enable continuous and stable delivery of drugs over a long period (months to years) and iii) to administer drugs directly to the lesion, thereby helping reduce dosage and side effects. iv) IDDSs enable personalized drug delivery according to patient needs. The high demand for such systems has prompted scientists to make efforts to develop intelligent IDDS. In this review, several common stimulus-responsive mechanisms including endogenous (e.g., pH, reactive oxygen species, proteins, etc.) and exogenous stimuli (e.g., light, sound, electricity, magnetism, etc.), are given in detail. Besides, several types of IDDS reported in recent years are reviewed, including various stimulus-responsive systems based on the above mechanisms, radio frequency-controlled IDDS, "closed-loop" IDDS, self-powered IDDS, etc. Finally, the advantages and disadvantages of various IDDS, bottleneck problems, and possible solutions are analyzed to provide directions for subsequent research.
Topics: Humans; Drug Delivery Systems; Animals; Drug Implants; Drug Liberation
PubMed: 38376369
DOI: 10.1002/adma.202312530