Aim The use of musculoskeletal ultrasound (MSK‐US) following protocols for haemophilic arthropathy and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD‐US) score can help standardize monitoring in haemophilia. This study evaluated the joint status (elbows, knees and ankles) of patients with haemophilia B (HB) in Spain using MSK‐US and the HEAD‐US score. Methods Haemophilia B patients ≥14 years old were included in this observational, multicentre, cross‐sectional study, regardless of their clinical condition, HB severity and treatment received. Two blinded observers were involved in image acquisition and scoring in each centre. Results Eighty‐two patients from 12 centres were enrolled: 27% mild HB, 23% moderate, 50% severe HB. Mean age was 38.9 ± 16.4 years, 60% were treated on demand (OD) and 40% were on prophylaxis. HEAD‐US was zero in all joints in 28.6% OD patients and 36.4% on prophylaxis. Mean scores significantly worsened with HB severity, except for the left knee. Patients on primary and secondary prophylaxis had significantly better joint health vs OD patients in all joints, except the right ankle. Among OD patients, those with severe disease presented significantly worse scores in all HEAD‐US items related to permanent damage. Conclusion Joint status of HB patients in Spain is influenced by severity and treatment modality, related to the development of arthropathy, which appears prevalent in OD patients with severe HB. Routine assessment with an imaging tool such as ultrasound and HEAD‐US system may help to improve joint health by personalizing and adjusting treatment in this population.
Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.
Fungal keratitis causes corneal blindness worldwide. The treatment includes antibiotics, with Natamycin being the most commonly used; however, fungal keratitis is difficult to treat, so alternative therapies are needed. In situ gelling formulations are a promising alternative; this type of formulation has the advantages of eye drops combined with the advantages of ointments. This study was designed to develop and characterize three formulations containing 0.5% CSP: CSP-O1, CSP-O2, and CSP-O3. CSP is an antifungal drug that acts against a diverse variety of fungi, and Poloxamer 407 (P407) is a polymer of synthetic origin that is able to produce biocompatible, biodegradable, highly permeable gels and is known to be thermoreversible. Short-term stability showed that formulations are best stored at 4 °C, and rheological analysis showed that the only formulation able to gel in situ was CSP-O3. In vitro release studies indicated that CSP-O1 releases CSP most rapidly, while in vitro permeation studies showed that CSP-O3 permeated the most. The ocular tolerance study showed that none of the formulations caused eye irritation. However, CSP-O1 decreased the cornea’s transparency. Histological results indicate that the formulations are suitable for use, with the exception of CSP-O3, which induced slight structural changes in the scleral structure. All formulations were shown to have antifungal activity. In view of the results obtained, these formulations could be promising candidates for use in the treatment of fungal keratitis.
Caspofungin is a drug that is used for fungal infections that are difficult to treat, including invasive aspergillosis and candidemia, as well as other forms of invasive candidiasis. The aim of this study was to incorporate Azone in a caspofungin gel (CPF-AZ-gel) and compare it with a promoter-free caspofungin gel (CPF-gel). An in vitro release study using a polytetrafluoroethylene membrane and ex vivo permeation into human skin was adopted. The tolerability properties were confirmed by histological analysis, and an evaluation of the biomechanical properties of the skin was undertaken. Antimicrobial efficacy was determined against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. CPF-AZ-gel and CPF-gel, which had a homogeneous appearance, pseudoplastic behavior, and high spreadability, were obtained. The biopharmaceutical studies confirmed that caspofungin was released following a one-phase exponential association model and the CPF-AZ gel showed a higher release. The CPF-AZ gel showed higher retention of caspofungin in the skin while limiting the diffusion of the drug to the receptor fluid. Both formulations were well-tolerated in the histological sections, as well as after their topical application in the skin. These formulations inhibited the growth of C. glabrata, C. parapsilosis, and C. tropicalis, while C. albicans showed resistance. In summary, dermal treatment with caspofungin could be used as a promising therapy for cutaneous candidiasis in patients that are refractory or intolerant to conventional antifungal agents.
The use of hydrogels in the treatment of wound healing is becoming an increasinglyroutine. [...]
Background: In recent years, a growing concern about resistance to anti-infective agents has emerged1. One of the most common microbial agents is Candida albicans. Under certain conditions, C. albicans can cause infections of skin and mucosal tissues. Nystatin (Nys) is a broad-spectrum antifungal, which is indicated for the treatment of mucosal infections caused by Candida ssp such as patients under radiological treatment. Nys is a photosensitive drug and very poorly soluble in aqueous media. Therefore, microencapsulation can be the solution for its limiting factors2–3. Purpose: The aim of this work was to design, develop and characterize two types of microparticles as appropriate nystatin delivery systems for topical use: alginate microparticles (AM) and chitosan coated alginate microparticles (CCM). Methods: The formulation of the microparticles was based on the emulsification/internal gelation methodology with modification4. First, a water in oil W/O emulsion was created. Sodium alginate aqueous solution, CaCO3 and Nys were the ingredients of the internal phase, and vegetable oil the external phase. The resulting microparticles were characterized in terms of particle size, percentage yield (PY), loading capacity (LD), encapsulation efficiency (EE) and mucoadhesion ability. Results and Discussion: Microparticles ranged from 51.21 μm for AM to 57.20 μm for CCM. The PY values were 83.26% and for 79.67% AM and CCM, respectively. The LD values for the inside/surface were 6.78%/0.40% for AM and 4.87%/0.91% for CCM. The values of EE for inside and surface were 81.12%/12.07% for AM and 85.08%/9.19% for CCM. CCM was the system that exhibited the best mucoadhesive properties. Conclusions: The ability of these systems to adhere to mucous membranes has great appeal for the treatment of localized infections. Thus, these microparticulate systems could be proposed as a suitable vehicle for this kind of mucosal infections, being an alternative therapy.
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