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Acta Biomaterialia Mar 2023The drive to develop cartilage implants for the treatment of major defects in the musculoskeletal system has resulted in a major research thrust towards developing... (Review)
Review
The drive to develop cartilage implants for the treatment of major defects in the musculoskeletal system has resulted in a major research thrust towards developing biomaterial devices for cartilage repair. Investigational devices for the restoration of articular cartilage are considered as significant risk materials by regulatory bodies and therefore proof of efficacy and safety prior to clinical testing represents a critical phase of the multidisciplinary effort to bridge the gap between bench and bedside. To date, review articles have thoroughly covered different scientific facets of cartilage engineering paradigm, but surprisingly, little attention has been given to the preclinical considerations revolving around the validation of a biomaterial implant. Considering hydrogel-based cartilage products as an example, the present review endeavors to provide a summary of the critical prerequisites that such devices should meet for cartilage repair, for successful implantation and subsequent preclinical validation prior to clinical trials. Considerations pertaining to the choice of appropriate animal model, characterization techniques for the quantitative and qualitative outcome measures, as well as concerns with respect to GLP practices are also extensively discussed. This article is not meant to provide a systematic review, but rather to introduce a device validation-based roadmap to the academic investigator, in anticipation of future healthcare commercialization. STATEMENT OF SIGNIFICANCE: There are significant challenges around translation of in vitro cartilage repair strategies to approved therapies. New biomaterial-based devices must undergo exhaustive investigations to ensure their safety and efficacy prior to clinical trials. These considerations are required to be applied from early developmental stages. Although there are numerous research works on cartilage devices and their in vivo evaluations, little attention has been given into the preclinical pathway and the corresponding approval processes. With a focus on hydrogel devices to concretely illustrate the preclinical path, this review paper intends to highlight the various considerations regarding the preclinical validation of hydrogel devices for cartilage repair, from regulatory considerations, to implantation strategies, device performance aspects and characterizations.
Topics: Animals; Hydrogels; Cartilage, Articular; Biocompatible Materials; Tissue Engineering
PubMed: 36638938
DOI: 10.1016/j.actbio.2023.01.015 -
Bioscience Reports Feb 2023Nanotechnology is an interdisciplinary domain of science, technology and engineering that deals with nano-sized materials/particles. Usually, the size of nanoparticles...
Nanotechnology is an interdisciplinary domain of science, technology and engineering that deals with nano-sized materials/particles. Usually, the size of nanoparticles lies between 1 and 100 nm. Due to their small size and large surface area-to-volume ratio, nanoparticles exhibit high reactivity, greater stability and adsorption capacity. These important physicochemical properties attract scientific community to utilize them in biomedical field. Various types of nanoparticles (inorganic and organic) have broad applications in medical field ranging from imaging to gene therapy. These are also effective drug carriers. In recent times, nanoparticles are utilized to circumvent different treatment limitations. For example, the ability of nanoparticles to cross the blood-brain barrier and having a certain degree of specificity towards amyloid deposits makes themselves important candidates for the treatment of Alzheimer's disease. Furthermore, nanotechnology has been used extensively to overcome several pertinent issues like drug-resistance phenomenon, side effects of conventional drugs and targeted drug delivery issue in leprosy, tuberculosis and cancer. Thus, in this review, the application of different nanoparticles for the treatment of these four important diseases (Alzheimer's disease, tuberculosis, leprosy and cancer) as well as for the effective delivery of drugs used in these diseases has been presented systematically. Although nanoformulations have many advantages over traditional therapeutics for treating these diseases, nanotoxicity is a major concern that has been discussed subsequently. Lastly, we have presented the promising future prospective of nanoparticles as alternative therapeutics. In that section, we have discussed about the futuristic approach(es) that could provide promising candidate(s) for the treatment of these four diseases.
Topics: Humans; Amyloid beta-Peptides; Alzheimer Disease; Nanoparticles; Drug Carriers; Tuberculosis; Neoplasms; Leprosy
PubMed: 36630532
DOI: 10.1042/BSR20220324 -
Neurologia I Neurochirurgia Polska 2023Polyneuropathy (PNP) is a known complication of levodopa-carbidopa intestinal gel (LCIG) therapy of advanced Parkinson's Disease (PD). The overall prevalence of PNP in...
Polyneuropathy (PNP) is a known complication of levodopa-carbidopa intestinal gel (LCIG) therapy of advanced Parkinson's Disease (PD). The overall prevalence of PNP in PD is estimated to be 42.1% (as shown in a review by Romagnolo et al. 2018), and the most common type is chronic axonal polyneuropathy. There is a group of acute/subacute onset demyelinating polyneuropathies, which is far less common, although it seems to be an important factor leading to the rapid discontinuation of LCIG treatment. In this systematic review, we present data on demyelinating polyneuropathy with acute/subacute onset; we identified nine papers including prospective assessments and case reports, with detailed information on 15 patients. In all patients, despite treatment with corticosteroids, intravenous immunoglobulins (IVIG) or plasma exchange (PE), the LCIG therapy was terminated. We also present a case of subacute demyelinating polyneuropathy with effective treatment and continuation of LCIG therapy.
Topics: Humans; Carbidopa; Levodopa; Parkinson Disease; Antiparkinson Agents; Prospective Studies; Polyneuropathies; Drug Combinations; Gels
PubMed: 36628506
DOI: 10.5603/PJNNS.a2023.0001 -
Nanotheranostics 2023Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy....
Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) were developed in response to the need for materials with high thermal, chemical, and mechanical properties. The synthesis, ease of surface functionalization, tunable pore size, large surface area, and biocompatibility of MSNs make them useful in a variety of biomedical applications such as drug delivery, theranostics, and stem cell research. In addition, MSNs have a high capability of delivering actives ranging from small molecules such as drugs and amino acids to larger peptides, vaccines, and antibodies in general. Moreover, MSN-based transdermal delivery has sparked a lot of interest because of the increase in drug stability, permeation, and ease of functionalization. The functionalization of MSNs plays an important role in the efficient delivery of therapeutic agents in a highly controlled manner. This review introduced dermal and transdermal drug delivery systems, explained the anatomy of the skin, and summarized different barriers that affect the transdermal delivery of many therapeutic agents. In addition, the fundamentals of MSNs together with their physicochemical properties, synthesis approaches, raw materials used in their fabrication, and factors affecting their physicochemical properties will be covered. Moreover, the applications of MSNs in dermal and transdermal delivery, the biocompatibility of MSNs in terms of toxicity and safety, and biodistribution will be explained with the help of a detailed literature review. The review is covering the current and future perspectives of MSNs in the pharmaceutical field with therapeutic applications.
Topics: Drug Carriers; Drug Delivery Systems; Nanoparticles; Porosity; Silicon Dioxide; Tissue Distribution
PubMed: 36593800
DOI: 10.7150/ntno.77395 -
PloS One 2022The prevalence of Mycobacterium avium complex (MAC) is increasing globally. Macrolide-based multidrug regimens have been recommended as the first-line treatment for...
INTRODUCTION
The prevalence of Mycobacterium avium complex (MAC) is increasing globally. Macrolide-based multidrug regimens have been recommended as the first-line treatment for patients with MAC pulmonary disease. However, developing macrolide resistance was associated with poor treatment outcomes and increased mortality. In 2018, the U.S. Food and Drug Administration approved liposomal amikacin for inhalation (LAI) to treat refractory MAC pulmonary disease. The current systematic review aimed to evaluate LAI's outcomes and adverse events in MAC pulmonary disease.
METHODS
The systematic search was performed in PubMed/Medline, EMBASE, and the Cochrane Controlled Register of Trials (CENTRAL) up to March 8, 2022. The search terms included Mycobacterium avium complex, MAC, amikacin, and liposomal amikacin.
RESULTS
After reviewing 1284 records, four papers met the inclusion criteria, including three clinical trials and one prospective cohort study. These studies showed that adding LAI to guideline-based therapies can increase sputum culture conversion rate and achieve early sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for three months after treatment) negative sputum culture. In addition, extended LAI use was a potential benefit in patients considered refractory to initial treatment. The most prevalent treatment-emergent adverse events (TEAE) reported in the LAI group were the respiratory TEAE.
CONCLUSIONS
LAI could increase the sputum culture conversion rate and achieve early sustainable, durable negative sputum culture. However, additional large-scale research is required to confirm the results.
Topics: Humans; Amikacin; Mycobacterium avium Complex; Anti-Bacterial Agents; Liposomes; Mycobacterium avium-intracellulare Infection; Prospective Studies; Macrolides; Drug Resistance, Bacterial; Lung Diseases
PubMed: 36574432
DOI: 10.1371/journal.pone.0279714 -
Multiple Sclerosis and Related Disorders Jan 2023Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and... (Review)
Review
BACKGROUND
Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and Year 2. Most patients achieve sustained efficacy with CladT, but a small proportion may experience new disease activity (DA). Following completion of the indicated dose, physicians may have questions relating to the long-term management of these patients. Since the EU approval of CladT over 5 years ago, real-world evidence (RWE) is increasing and may provide some insights and guidance for clinical practice. We describe a systematic literature review (SLR) of RWE and provide expert opinions relating to six questions regarding the long-term use of CladT.
METHODS
Pertinent clinical questions were developed by a steering committee (SC) of 14 international multiple sclerosis (MS) experts regarding breakthrough DA in Year 1, new DA after 2 years or more of treatment, long-term management of stable patients, and whether additional courses of CladT may be required or safe. An SLR was performed in EMBASE and PubMed using the population, intervention, comparators, outcomes, study design (PICOS) framework to identify relevant studies within the last 15 years. Searches of key congress proceedings for the last 2-3 years were also performed. Following review of the results and RWE, the SC drafted and agreed on expert opinion statements for each question.
RESULTS
A total of 35 publications reporting RWE for CladT were included in this review. In the real world, breakthrough DA in Year 1 is of low incidence (1.1-21.9%) but can occur, particularly in patients switching from anti-lymphocyte trafficking agents. In most patients, this DA did not lead to treatment discontinuation. Reported rates of DA after the full therapeutic effect of CladT has been achieved (end of Year 2, 3 or 4) range from 12.0 to 18.7% in the few studies identified. No RWE was identified to support management decisions for stable patients in Year 5 or later. Views among the group were also diverse on this question and voting on expert opinion statements was required. Only two studies reported the administration of additional courses of CladT, but detailed safety outcomes were not provided.
CONCLUSIONS
RWE for the long-term use of CladT in the treatment of RMS is increasing, however, gaps in knowledge remain. Where possible, the RWE identified through the SLR informed expert statements, but, where RWE is still lacking, these were based solely on experiences and opinion, providing some guidance on topics and questions that occur in daily clinical practice. More real-world studies with longer-term follow-up periods are needed and highly anticipated.
Topics: Humans; Cladribine; Multiple Sclerosis; Expert Testimony; Lymphocytes; Tablets; Recurrence; Immunosuppressive Agents
PubMed: 36565573
DOI: 10.1016/j.msard.2022.104459 -
Cells Dec 2022This systematic review is focused on the main characteristics of the hydrogels used for embedding the mesenchymal stromal cells (MSCs) in in vitro/ex vivo studies, in... (Review)
Review
This systematic review is focused on the main characteristics of the hydrogels used for embedding the mesenchymal stromal cells (MSCs) in in vitro/ex vivo studies, in vivo OA models and clinical trials for favoring cartilage regeneration in osteoarthritis (OA). PubMED and Embase databases were used to select the papers that were submitted to a public reference manager Rayyan Systematic Review Screening Software. A total of 42 studies were considered eligible: 25 articles concerned in vitro studies, 2 in vitro and ex vivo ones, 5 in vitro and in vivo ones, 8 in vivo ones and 2 clinical trials. Some in vitro studies evidenced a rheological characterization of the hydrogels and description of the crosslinking methods. Only 37.5% of the studies considered at the same time chondrogenic, fibrotic and hypertrophic markers. Ex vivo studies focused on hydrogel adhesion properties and the modification of MSC-laden hydrogels subjected to compression tests. In vivo studies evidenced the effect of cell-laden hydrogels in OA animal models or defined the chondrogenic potentiality of the cells in subcutaneous implantation models. Clinical studies confirmed the positive impact of these treatments on patients with OA. To speed the translation to the clinical use of cell-laden hydrogels, further studies on hydrogel characteristics, injection modalities, chemo-attractant properties and adhesion strength are needed.
Topics: Animals; Hydrogels; Cartilage; Mesenchymal Stem Cells; Osteoarthritis; Models, Animal
PubMed: 36552733
DOI: 10.3390/cells11243969 -
Turkish Journal of Pharmaceutical... Dec 2022Biopharmaceutical classification system (BCS) is an advanced tool used for classifying medicines based on dissolution, water solubility, and intestinal permeability,...
Biopharmaceutical classification system (BCS) is an advanced tool used for classifying medicines based on dissolution, water solubility, and intestinal permeability, which affect the absorption of active pharmaceutical ingredients (API) from immediate-release solid oral forms. It is useful to the formulation researchers to develop novel dosage forms based on modernistic rather than experimental approaches. The current review focuses on the fundamentals, objectives, guidance of BCS, characteristics of BCS drugs, their importance and applications of BCS. This review explains the challenges in drug development in terms of solubility and in vivo disposition. In the current review, new strategies for improving BCS II drug solubility as well as biopharmaceutical drug disposition properties which are utilized throughout the early stages of drug development and commercialization are mainly discussed.
PubMed: 36544401
DOI: 10.4274/tjps.galenos.2021.73554 -
Translational Psychiatry Dec 2022Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise... (Meta-Analysis)
Meta-Analysis
Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise and network meta-analysis that compared PP (25-150 mg equivalent) with paliperidone extended-release (PAL-ER, 3-12 mg/d) regarding their efficacy and safety in adults with acute symptoms of schizophrenia. The outcomes were the total score of the Positive and Negative Syndrome Scale (PANSS-T) at week 6 (the primary outcome for efficacy) and all-cause discontinuation(the primary outcome for acceptability), discontinuation due to inefficacy, discontinuation due to adverse events, discontinuation due to the withdrawal of consent, and the incidence of individual adverse events. Five studies on PP and seven studies on PAL-ER, which involved 4970 individuals in total, were included in this study. For the primary outcomes, we only included data from the treatment arms that used 100 or 150 mg equivalent as an initial dose of PP and data from the treatment arms that used 6, 9, or 12 mg as an initial dose of PAL-ER. The pairwise meta-analyses showed that both PP and PAL-ER outperformed placebo regarding PANSS-T at week 6 and all-cause discontinuation. However, there were no statistically significant differences in these outcomes between the effect sizes of PP and that of PAL-ER. Both PP and PAL-ER increased blood prolactin levels in both females and males compared with placebo. PAL-ER significantly increased blood prolactin in both females and males compared with PP. There were no statistically significant differences in other outcomes between the effect sizes of PP and that of PAL-ER. Similar results in all outcomes were observed in the network meta-analyses. In conclusion, PP might be a useful treatment option for adults with acute symptoms of schizophrenia. A noninferiority study that directly compares PP with PAL-ER for acute schizophrenia, conducted according to the recommended regimen, is required to provide solid evidence.
Topics: Male; Female; Adult; Humans; Paliperidone Palmitate; Schizophrenia; Network Meta-Analysis; Antipsychotic Agents; Prolactin; Isoxazoles; Pyrimidines; Delayed-Action Preparations; Treatment Outcome
PubMed: 36535950
DOI: 10.1038/s41398-022-02286-1 -
Journal of Orthopaedic Surgery and... Dec 2022Periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) is a serious complication for patients. Some joint surgeons have tried to use vancomycin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) is a serious complication for patients. Some joint surgeons have tried to use vancomycin powder (VP) in total knee and total hip arthroplasty to prevent postoperative PJI, but its effect is still not clear. At present, there is no meta-analysis that specifically analyses the effect of different doses of vancomycin powder on the incidence of PJI.
METHODS
We carried out a search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and identified the studies we needed. Review Manager (RevMan) 5.3 software was employed for statistical analysis.
RESULTS
The analysis of primary TKA (PTKA) showed that using 1 g (RR 0.38, 95% CI 0.22-0.67 [P = 0.0008]) and 2 g (RR 0.48, 95% CI 0.31-0.74 [P = 0.0008]) of vancomycin powder in primary TKA (PTKA) could all significantly prevent PJI. The analysis of primary THA (PTHA) showed that using 1 g (RR 0.37, 95% CI 0.17-0.80 [P = 0.01]) of vancomycin powder effectively decreased the incidence of PJI, while using 2 g (RR 1.02, 95% CI 0.53-1.97 [P = 0.94]) of vancomycin powder had no significant effect on preventing PJI. Because the data were abnormal, we believed the conclusion that using 2 g of vancomycin powder in primary THA had no effect on preventing PJI was doubtful. Using vancomycin powder in revision TKA (RTKA) significantly reduced the PJI rate (RR 0.33, 95% CI 0.14-0.77 [P = 0.01]), similar to revision THA (RTHA) (RR 0.37, 95% CI 0.14-0.96 [P = 0.04]).
CONCLUSIONS
In primary TKA, both 1 g and 2 g of vancomycin powder can effectively prevent PJI. In primary THA, using 1 g of vancomycin powder is a better choice, while the effect of using 2 g of vancomycin powder is not clear, and a more prospective randomized controlled trial should be done to verify it. In revision TKA and revision THA, vancomycin powder is a good choice to prevent PJI.
Topics: Humans; Arthroplasty, Replacement, Hip; Vancomycin; Prosthesis-Related Infections; Arthroplasty, Replacement, Knee; Powders; Prospective Studies; Arthritis, Infectious; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 36527075
DOI: 10.1186/s13018-022-03445-2