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Medicina (Kaunas, Lithuania) Nov 2023Knee osteoarthritis (OA) is a widespread joint disease, set to increase due to aging and rising obesity. Beyond cartilage degeneration, OA involves the entire joint,... (Review)
Review
Knee osteoarthritis (OA) is a widespread joint disease, set to increase due to aging and rising obesity. Beyond cartilage degeneration, OA involves the entire joint, including the synovial fluid, bones, and surrounding muscles. Existing treatments, such as NSAIDs and corticosteroid injections, mainly alleviate symptoms but can have complications. Joint replacement surgeries are definitive but carry surgical risks and are not suitable for all. Stromal vascular fraction (SVF) therapy is a regenerative approach using cells from a patient's adipose tissue. SVF addresses as degenerative and inflammatory aspects, with potential for cartilage formation and tissue regeneration. Unlike traditional treatments, SVF may reverse OA changes. Being autologous, it reduces immunogenic risks. A systematic search was undertaken across PubMed, Medline, and Scopus for relevant studies published from 2017 to 2023. Keywords included "SVF", "Knee Osteoarthritis", and "Regenerative Medicine". This systematic search yielded a total of 172 articles. After the removal of duplicates and an initial title and abstract screening, 94 full-text articles were assessed for eligibility. Of these, 22 studies met the inclusion criteria and were subsequently included in this review. This review of SVF therapy for knee OA suggests its potential therapeutic benefits. Most studies confirmed its safety and efficacy, and showed improved clinical outcomes and minimal adverse events. However, differences in study designs and sizes require a careful interpretation of the results. While evidence supports SVF's positive effects, understanding methodological limitations is key. Incorporating SVF is promising, but the approach should prioritize patient safety and rigorous research.
Topics: Humans; Osteoarthritis, Knee; Stromal Vascular Fraction; Injections; Adipose Tissue
PubMed: 38138193
DOI: 10.3390/medicina59122090 -
Pharmaceutical Medicine Nov 2023Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usually the plasma. This... (Review)
Review
Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usually the plasma. This is as close to the tissue of interest that we can get, although biopsies may be obtained to give "tissue levels" of drugs. Ultimately, the goal of PK is to understand how long the drug is actually engaged with the target in the tissue of interest after a dose has been administered. Most drugs at some point in their development will have been administered intravenously (IV), which acts as the standard for 100% bioavailability. By comparing various routes of administration to IV, the percentage of drug delivered to the plasma, on a dose-normalized basis, can be calculated and is referred to as the "absolute bioavailability". As pharmacology has advanced and more drugs have become available, many older products have been reformulated to be given by routes other than those originally intended (often oral). As the drawbacks of oral (or IV) administration have become better appreciated, non-oral, non-IV formulations and methods of administration have become more popular. Nasal administration is one route that has historically been overlooked as an alternative to oral administration-particularly for products needing rapid and non-invasive access to the target tissue-mostly via the blood stream. But attention is now focused on nasal administration for direct access to the brain, as that has the potential to bypass the blood-brain-barrier (BBB), which not even IV administration can always achieve. Assessing PK for these drugs targeting the brain may require serial sampling of the cerebrospinal fluid (CSF), making PK assessments of CNS drugs more invasive and complex, but still possible in future product development. However, we are now seeing more drugs reformulated for nasal delivery to gain faster systemic levels than oral administration (especially in patients with known or suspected gastrointestinal dysmotility), while avoiding the use of needles. For example, in recent years several different formulations and delivery methods for an old drug, dihydroergotamine (DHE), have been developed and these show very different characteristics, suggesting that delivery to different parts of the nose may have very different PK profiles. This review summarizes the systemic PK of different nasal DHE options that have been, or are being, developed and suggests that delivery of drugs to the upper nasal space (UNS) may represent an optimal target. Further research is required to ascertain if this route could also be utilized for direct administration to the CNS (as an attractive alternative to intrathecal delivery) via the olfactory or trigeminal nerves-but already preclinical data (and some human data) suggest this is entirely possible.
Topics: Humans; Pharmaceutical Preparations; Administration, Intranasal; Brain; Blood-Brain Barrier; Central Nervous System Agents
PubMed: 37537422
DOI: 10.1007/s40290-023-00495-7 -
Medicine Sep 2023A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage. (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage.
METHODS
Electronic databases (Pubmed, Embase, Web of Science and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different administration route of nimodipine (intravenous and enteral) versus placebo for treatment subarachnoid hemorrhage. Outcomes included case fatality at 3 months, poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), incidence of delayed cerebral ischemia (DCI), delayed ischemic neurological deficit. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
Nine randomized controlled trials met criteria for inclusion and finally included in this NMA. There was no statistically significant between intravenous and enteral in terms of case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P > .05). Both intravenous and enteral could reduce case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P < .05). The SUCRA shows that enteral ranked first, intravenous ranked second and placebo ranked the last for case fatality, the occurrence of DCI and poor outcomes. The SUCRA shows that intravenous ranked first, enteral ranked second and placebo ranked the last for delayed ischemic neurologic deficit.
CONCLUSIONS
It is possible that both enteral and intravenous nimodipine have comparable effectiveness in preventing poor outcomes, DCI, and delayed ischemic neurological deficits. However, further investigation may be necessary to determine the exact role of intravenous nimodipine in current clinical practice.
Topics: Humans; Nimodipine; Subarachnoid Hemorrhage; Network Meta-Analysis; Bayes Theorem; Administration, Intravenous; Brain Ischemia; Cerebral Infarction
PubMed: 37773855
DOI: 10.1097/MD.0000000000034789 -
Advanced Drug Delivery Reviews Jul 2023Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and... (Review)
Review
Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and physiological barriers while minimising tissue toxicity has restricted developments in this field. Aqueous vehicles have traditionally been used, which typically require several additives and preservatives to achieve physiologically compatible and sterile eyedrops, elevating their toxicity potential. Non-aqueous vehicles have been suggested as efficient alternatives for topical drug delivery as they can address many of the limitations associated with conventional aqueous eyedrops. However, despite their obvious advantages, non-aqueous eyedrops remain poorly researched and few non-aqueous formulations are currently available in the market. This review challenges the conventional hypothesis that aqueous solubility is a prerequisite to ocular drug absorption and establishes a rationale for using non-aqueous vehicles for ocular drug delivery. Recent advances in the field have been detailed and future research prospects have been explored, pointing towards a paradigm shift in eyedrop formulation in the near future.
Topics: Humans; Administration, Topical; Eye; Drug Delivery Systems; Ophthalmic Solutions
PubMed: 37178927
DOI: 10.1016/j.addr.2023.114867 -
Drug Delivery Dec 2023Diseases affecting the esophagus are common. However, targeted drug delivery to the esophagus is challenging due to the anatomy and physiology of this organ. Current... (Review)
Review
Diseases affecting the esophagus are common. However, targeted drug delivery to the esophagus is challenging due to the anatomy and physiology of this organ. Current pharmacological treatment for esophageal diseases predominantly relies on the off-label use of drugs in various dosage forms, including those for systemic drug delivery (e.g. oral tablets, sublingual tablets, and injections) and topical drug delivery (e.g. metered dose inhaler, viscous solution or suspension, and endoscopic injection into the esophagus). In general, systemic therapy has shown the most efficacy but requires the use of high drug doses to achieve effective concentrations in the esophagus, which increases the risk of adverse effects and toxicity. Topical drug delivery has enormous potential in improving the way we treat patients with acute and chronic esophageal diseases, especially those requiring drugs that have low therapeutic index and/or significant adverse effects to non-targeted organs and tissues. This review will address the physiological, pathophysiological, and pharmaceutical considerations influencing topical drug delivery in the esophagus. The main conventional (e.g. liquid formulations, orodispersible tablets, lozenges, pastilles, troches, chewing gum) and innovative (e.g. stent-based, film-based, nanoparticulate-based) drug delivery approaches will be comprehensively discussed, along with the developments to improve their effectiveness for topical esophageal drug delivery. The translational challenges and future clinical advances of this research will also be discussed.
Topics: Humans; Drug Delivery Systems; Tablets; Esophageal Diseases; Administration, Inhalation
PubMed: 37344759
DOI: 10.1080/10717544.2023.2219423 -
International Journal of Nanomedicine 2024Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those... (Review)
Review
Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those characterized by poor solubility in both aqueous and organic environments. Addressing solubility issues associated with poorly water-soluble drugs has largely resolved the need to enhance drug absorption and bioavailability. As mucosal formulations and topical administration progress in the future, nanosuspension drug delivery, straightforward formulation techniques, and versatile applications will continue to be subjects of interest. Nanosuspensions have undergone extensive scrutiny in preparation for topical applications, encompassing ocular, pulmonary, and dermal usage. Among the numerous methods aimed at improving cutaneous application, nanocrystals represent a relatively recent yet profoundly intriguing approach. Despite the increasing availability of various nanosuspension products, primarily designed for oral administration, only a limited number of studies have explored skin permeability and drug accumulation in the context of nanosuspensions. Nevertheless, the scant published research unequivocally underscores the potential of this approach for enhancing cutaneous bioavailability, particularly for active ingredients with low to medium solubility. Nanocrystals exhibit increased skin adhesiveness in addition to heightened saturation solubility and dissolution rate, thereby augmenting cutaneous distribution. The article provides a comprehensive overview of nanosuspensions for topical application. The methodology employed is robust, with a well-defined experimental design; however, the limited sample size raises concerns about the generalizability of the findings. While the results demonstrate promising outcomes in terms of enhanced drug delivery, the discussion falls short of addressing certain limitations. Additionally, the references largely focus on recent studies, but a more diverse inclusion of historical perspectives could offer a more holistic view of the subject.
Topics: Humans; Suspensions; Drug Delivery Systems; Biological Availability; Nanoparticles; Administration, Oral; Solubility; Particle Size
PubMed: 38293608
DOI: 10.2147/IJN.S447429 -
Journal of Nanobiotechnology Jul 2023It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best... (Review)
Review
It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.
Topics: Humans; Pulmonary Fibrosis; Gold; Administration, Inhalation; COVID-19; Metal Nanoparticles; Drug Delivery Systems; Lung; Pharmaceutical Preparations; Nanoparticles
PubMed: 37422665
DOI: 10.1186/s12951-023-01971-7 -
Journal of Controlled Release :... Nov 2023The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of... (Review)
Review
The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of nanomedicine formulations. In contrast, while the oral route is the most favorable administration method for pharmaceuticals, little is known about the formation and composition of the corona formed by biomolecules on particles within the gastrointestinal tract. This work reviews the current literature understanding of (1) the formation of drug particles after oral administration, (2) the formation of a biomolecular corona within the gastrointestinal tract ("the gastrointestinal corona"), and (3) the possible implications of the formation of a gastrointestinal corona on the interactions of drug particles with their biological environment. In doing so, this work aims to establish the significance of the formation of a gastrointestinal corona in oral drug delivery to ultimately arrive at new avenues to control the behavior of orally administered pharmaceuticals.
Topics: Tissue Distribution; Nanoparticles; Gastrointestinal Tract; Administration, Oral; Pharmaceutical Preparations
PubMed: 37776905
DOI: 10.1016/j.jconrel.2023.09.049 -
Asia-Pacific Journal of Ophthalmology...This review discusses emerging approaches to ocular drug delivery for retinal diseases. Intravitreal injections have proven to be an effective, safe, and commonly used... (Review)
Review
This review discusses emerging approaches to ocular drug delivery for retinal diseases. Intravitreal injections have proven to be an effective, safe, and commonly used drug delivery method. However, the optimal management of chronic retinal diseases requires frequent intravitreal injections over extended periods of time. Although this can be achieved in a clinical trial environment, it is difficult to replicate in routine clinical practice. In addition, frequent treatment increases the risk of complications, incurs more costs, and increases the treatment burden for patients and caregivers. Given the aging global population and diabetes pandemic, there is an urgent need for drug delivery methods that support more durable retinal therapy while maintaining the efficacy and safety of currently available intravitreal therapies. Several innovative drug delivery methods are currently being investigated. These include sustained-release implants and depots using prodrugs, microparticles, and hydrogels, surgically implanted reservoirs, gene therapy via submacular injections or suprachoroidal injections, as well as topical and systemic therapies.
Topics: Humans; Pharmaceutical Preparations; Retinal Diseases; Drug Delivery Systems; Retina; Intravitreal Injections
PubMed: 37523432
DOI: 10.1097/APO.0000000000000623 -
The Israel Medical Association Journal... May 2024
Topics: Humans; Precision Medicine; Administration, Intranasal; Adrenal Cortex Hormones
PubMed: 38736351
DOI: No ID Found