The postoperative outcomes of patients with chronic rhinosinusitis with nasal polyps by sustained released steroid from hyaluronic acid gel.

PURPOSE: The self-crosslinked hyaluronic acid (scHA) and steroids are considered as efficient factors for postoperative management after chronic rhinosinusitis (CRS) nasal surgery. This randomized clinical trial is designed to investigate the efficacy and potential of scHA gel as a topical drug sustained release carrier for steroid of budesonide. METHODS: The study is performed with 30 patients of chronic rhinosinusitis with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS). The single application of scHA was assessed in the control patient group for postoperative recovery. In the treatment patient group, the combination of scHA/budesonide was applied for postoperative management. The patients are followed up in 2 weeks, 4 weeks and 12 weeks after surgery. RESULTS: The combination of scHA/budesonide results in better endoscopic scoring and mucus evaluation than the single scHA application. CONCLUSION: The results indicate that the combination of scHA/budesonide is a valuable treatment for the FESS postoperative management and implies the potential of scHA gel as a topical drug sustained release scaffold.

Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release.

AIMS: Crosslinked hyaluronic acid (X-linked HA) is not suitable for making microneedles because of the low fluidity of X-linked HA hydrogel. Microneedles were fabricated using X-linked HA nanoparticles (X-linked HA-NPs) to utilize the sustained drug delivery capability of X-linked HA-NPs and to obtain the processability advantages of X-linked HA. METHOD: The puncture performance of a microneedle array patch (MAP) made of crosslinked hyaluronic acid nanoparticles (X-linked HA-NP-MAP) was evaluated by insertion in vitro into porcine skin. After a predetermined attachment time, the remaining height of the X-linked HA-NP-MAP was measured to determine the dissolution rate. X-linked HA-NP-MAP and free HA-MAP containing Rhodamine B isothiocyanate-dextran were administered into the back skin of mice, and the relative fluorescent intensity in the back skin was measured over time. RESULTS: The puncture performance of the X-linked HA-NP-MAP was over 90%. The diameter of redispersed X-linked HA-NPs was same as that of the premolded X-linked HA-NPs. The dissolution rate was not different from that of free HA-MAP. In an in vivo experiment, X-linked HA-NP-MAP was administered into the mouse's back skin successfully and the relative fluorescent intensity of X-linked HA-NP-MAP lasted longer than that of HA-MAP. CONCLUSION: X-linked HA-NPs provide the biocompatibility, the processability of micromolding, sustained drug release, successful penetration into the skin, and relatively short insertion time for full disintegration of NPs in the skin. X-linked HA-NP-MAP can be used for various applications that require several days of sustained drug release.

Bipolar Radiofrequency and Non-Crosslinked Hyaluronic Acid Plus Calcium Hydroxyapatite in the Treatment of Stress Urinary Incontinence.

BACKGROUND: Stress urinary incontinence (SUI) causes both physical and psychological problems to women and their partners. Recently, vaginal radiofrequency (RF) application, as well as the administration of non-crosslinked hyaluronic acid (NCLHA) together with calcium hydroxyapatite (CaHA), has attracted attention for SUI treatment. The current, comparative study evaluated the efficacy and safety of these technologies acting separately and in a combined treatment. METHODS: Sixty women with mild to moderate SUI, aged between 46 and 76 years (mean age 63.2) were divided into three groups intended for different treatments: group I, RF vaginal treatment only, group II, NCLHA plus CaHA periurethral injection only, group III, combined treatment including a single periurethral injection of NCLHA plus CaHA followed by four vaginal applications of RF at intervals of 3-5 days. The clinical effects of the treatments were evaluated by ICIQ-LUTSqol (Polish version) and UDI-6. RESULTS: The obtained results suggest that the symptoms of SUI and the quality of life of the patients improved significantly in each group after the therapies compared to the pre-treatment levels and were more persistent in the third HA + RF group compared to the HA or the RF group.

Efficacy assessment of liposome crosslinked hyaluronic acid and standard hyaluronic acid eye drops for dry eye disease management: a comparative study employing the ocular surface analyzer and subjective questionnaires.

Introduction: Dry eye disease (DED) is a prevalent condition causing ocular discomfort and visual disturbances, often managed with artificial tears. This study aimed to assess and compare the efficacy of eye drops containing Crosslinked Hyaluronic Acid (CHA) with liposomes and crocin and standard Hyaluronic Acid (HA) for DED management. Methods: A single-blind, longitudinal study was conducted on 24 participants (48 eyes), randomized to receive one of the two treatments. Ocular health measures, including the ocular surface disease index (OSDI) and the standard patient evaluation of eye dryness (SPEED) scores, were assessed at baseline and 6 weeks post-treatment using the Ocular Surface Analyzer. Results: CHA achieved a lipid layer thickness increase of 1.29 ± 1.08 Guillon pattern degree (p < 0.01), FNIBUT increase 0.64 ± 0.77 s (p < 0.01), MNIBUT increase1.28 ± 4.74 s (p = 0.19), OSDI decrease 11.72 ± 6.73 score points (p < 0.01) and SPEED decrease 1.16 ± 5.05 score points (p = 0.27). Significant reductions in the OSDI and SPEED scores post-treatment were observed with both treatments, indicating their effectiveness. Conclusion: CHA with liposomes exhibits superior efficacy compared to standard HA eye drops in the management of DED. These findings highlight the potential for personalized treatment strategies incorporating CHA, indicating a more effective approach to DED management. However, further research is required to validate these results and investigate the long-term effects, which may pave the way for a data-driven and optimized approach to managing DED.

Combined Bipolar Radiofrequency and Non-Crosslinked Hyaluronic Acid Mesotherapy Protocol to Improve Skin Appearance and Epidermal Barrier Function: A Pilot Study.

BACKGROUND: Age-associated changes in epidermal hydration, pigmentation, thickness and cell renewal influence skin appearance and can lead to laxity, dryness and poor skin tone. The aim of this pilot study was to assess the synergistic effects of a new bipolar radiofrequency plus non-crosslinked hyaluronic acid (HA) mesotherapy protocol compared with radiofrequency alone on skin appearance and markers of epidermal function. METHODS: This prospective, single-center, split-face pilot study recruited women aged 25-65 years with dryness and laxity of the facial skin defined by a trans-epidermal water loss (TEWL) value of ≥26 g/m2/h. Subjects were treated with a bipolar radiofrequency device on both sides of the face. This was immediately followed by needle hyaluronic acid (HA) treatment on one side of the face with 2.5 mL of a non-crosslinked HA. Photographic documentation, analysis of epidermal barrier function parameters, and high frequency (HF) ultrasound analysis were performed prior to treatment and at 28 days. RESULTS: Twenty female subjects with a mean age of 46 (range 29 to 54) years and dry and lax facial skin were included. TEWL was reduced and skin hydration improved to a greater extent with the combined radiofrequency plus mesotherapy protocol compared with radiofrequency alone (-5.8% vs. +3.9% and +23.1% vs. +1.0%, respectively). The combined protocol was also associated with greater improvements in melanin (-7.5% vs. -1.5%) and erythema values (-7.2% vs. +3.0%), respectively. Ultrasound measures of epidermal thickness and epidermal density were greater after the combined protocol compared with radiofrequency alone (12.0% vs. 5.6% and 57.7% vs. 7.1%, respectively). Both treatments were well-tolerated. CONCLUSIONS: The combined bipolar radiofrequency and HA mesotherapy protocol provided greater improvements in skin hydration, firmness and tone compared with radiofrequency alone. The combination treatment was also associated with greater epidermal thickness and density and increased keratinocyte differentiation suggesting a synergistic effect of both treatments on epidermal homeostasis and barrier function. Both treatments were well-tolerated and led to improvements in facial appearance.

A hyaluronic acid-based micro-filler improves superficial wrinkles and skin quality: a randomized prospective controlled multicenter study.

BACKGROUND: NCTF®135HA is a bio-revitalizing solution containing hyaluronic acid designed to compensate for skin dehydration, fatigue, and fine wrinkles associated with endogenous and environmental aging. METHODS: We conducted a randomized, active-controlled study to evaluate the efficacy and tolerability of NCTF®135HA injections on the face (crow's feet), neck, and décolleté regions. Subjects were randomly assigned (3:1) to receive three NCTF®135HA treatment sessions plus twice-daily anti-aging moisturizer cream or cream alone (control). The primary outcome was the reduction in superficial wrinkles between baseline and Day (D)75 in the three areas, assessed by profilometric measures, clinical scoring, subjective changes, and tolerability. RESULTS: 146 subjects were randomized to NCTF®135HA (n = 107) or control (n = 38). At D75 and D120, NCTF®135HA significantly reduced wrinkles in all three areas and improved facial radiance scores compared with the control. Skin hydration significantly increased 7 d after the last NCTF®135HA injection. Self-esteem scales showed statistically significant improvements at D75 and D120 in subjects treated with NCTF®135HA versus baseline. Most adverse events were mild, resolved within 48 h, and were related to the injection procedure. CONCLUSION: NCTF®135HA is an effective and well-tolerated treatment to reduce the skin signs of aging. The results are significantly superior to a routine anti-aging cream alone.(Funded by Laboratories FILLMED; ID-RCB number: 2018-A03167-48; clinicaltrials.gov number: NCT05609617).

Double-layer adhesives for preventing anastomotic leakage and reducing post-surgical adhesion.

Preventing anastomotic leakage (AL) and postoperative adhesions after gastrointestinal surgery is crucial for ensuring a favorable surgical prognosis. However, AL prevention using tissue adhesives can unintentionally lead to undesirable adhesion formation, while anti-adhesive agents may interfere with wound healing and contribute to AL. In this study, we have developed a double-layer patch, consisting of an adhesive layer on one side, utilizing gallic acid-conjugated chitosan (CHI-G), and an anti-adhesive layer on the opposite side, employing crosslinked hyaluronic acid (cHA). These CHI-G/cHA double-layer adhesives significantly prevented AL by forming physical barriers of CHI-G and reduced post-surgical adhesion at the anastomosis sites by the anti-adhesive layers of cHA. The bursting pressure (161.1 ± 21.6 mmHg) of double-layer adhesives-applied rat intestine at postoperative day 21 was far higher than those of the control (129.4 ± 5.7 mmHg) and the commercial anti-adhesives-applied group (120.8 ± 5.2 mmHg). In addition, adhesion score of double-layer adhesives-applied rat intestine was 3.6 ± 0.3 at postoperative day 21, which was similar to that of the commercial anti-adhesives-applied group (3.6 ± 0.3) and lower than that of the control group (4.9 ± 0.5). These findings indicate that the double-layer patch (CHI-G/cHA) has the potential to effectively prevent both postoperative adhesions and anastomotic leakage, offering a promising solution for gastrointestinal surgery.

Efficacy of 0.1% crosslinked hyaluronic acid, coenzyme Q10 and vitamin E in the management of dry eye disease in menopause patients receiving antidepressants.

PURPOSE: The purpose of this study is to test non-inferiority of a lower dose of crosslinked hyaluronic acid (CLHA) to a higher dose of carmellose eye drop in menopause patients receiving antidepressant treatments. METHODS: This prospective, double-blind, single-center study enrolled sixty female patients. Mean age was 63.25 ± 9.13 years. We examined patients with Schirmer I, breakup time (TBUT) and the ocular surface disease index (OSDI) at the first visit. Tear A eyedrops were formulated with crosslinked hyaluronic acid, coenzyme Q10 and vitamin E. Control tear B was formulated with carmellose sodium. Posology was two and five times, respectively. RESULTS: After 2 months of treatment, the tear A obtained 14.12 ± 7.47 score points for OSDI (t = 11.74, p < 0.01), and tear B obtained 19.46 ± 10.03 score points (t = 7.59, p < 0.01). The tear A obtained 13.77 ± 7.78 score points for Schirmer test (t = 0.88, p > 0.05), and tear B obtained 14.20 ± 8.62 score points (t = 2.92, p < 0.01). The tear A obtained 8.30 ± 2.08 s for TBUT (t = 15.50, p < 0.01), and tear B obtained 7.23 ± 2.40 s (t = 8.79, p < 0.01). CONCLUSION: Lower total daily dose of crosslinked hyaluronic acid eyedrops obtained similar efficacy results in terms of tear stability and subjective dry eye sensation than higher carmellose total daily dose. A lower total daily dose of crosslinked eyedrops was sufficient to achieve better dry eye disease management compared to carmellose.

Application of Injectable, Crosslinked, Fibrin-Containing Hyaluronic Acid Scaffolds for In Vivo Remodeling.

The present research aimed to characterize soft tissue implants that were prepared with the use of crosslinked hyaluronic acid (HA) using two different crosslinkers and multiple reagent concentrations, alone or in combination with fibrin. The effect of the implants was evaluated in an in vivo mouse model, after 4 weeks in one group and after 12 weeks in the other. The explants were compared using analytical methods, evaluating microscopic images, and a histology analysis. The kinetics of the degradation and remodeling of explants were found to be greatly dependent on the concentration and type of crosslinker; generally, divinyl sulfone (DVS) resists degradation more effectively compared to butanediol diglycidyl ether (BDDE). The presence of fibrin enhances the formation of blood vessels, and the infiltration of cells and extracellular matrix. In summary, if the aim is to create a soft tissue implant with easier degradation of the HA content, then the use of 2-5% BDDE is found to be optimal. For a longer degradation time, 5% DVS is the more suitable crosslinker. The use of fibrin was found to support the biological process of remodeling, while keeping the advances of HA in void filling, enabling the parallel degradation and remodeling processes.

Lipid, Aqueous and Mucin Tear Film Layer Stability and Permanence within 0.15% Liposome Crosslinked Hyaluronic Acid versus 0.15% Non-Crosslinked Hyaluronic Acid Measured with a Novel Non-Invasive Ocular Surface Analyzer.

To evaluate the stability and permanence of the liquid film created after the instillation of 0.15% crosslinked hyaluronic acid with liposomes and crocin versus the effect of 0.15% standard hyaluronic acid, a prospective, longitudinal, single-blind, single-center study was conducted in symptomatic populations with a novel noninvasive ocular surface analyzer. Limbal and bulbar redness classification, lipid layer thickness, tear meniscus height, and first and mean noninvasive break-up time (FNIBUT and MNIBUT) were performed before and 30 and 45 min after liposome-crosslinked hyaluronic acid (LCHA) and standard hyaluronic acid (HA) eye drop instillations. LCHA had a higher lipid layer thickness than HA (grades 2.00 ± 0.83 and 1.17 ± 0.63 on the Guillon pattern, respectively). LCHA achieved a better tear meniscus height than HA (0.23 ± 0.02 and 0.21 ± 0.02 mm, respectively). LCHA improved FNIBUT and MNIBUT more than HA (for FNIBUT, 6.30 ± 0.94 and 4.77 ± 0.89 s, respectively. For MNIBUT, 17.23 ± 5.11 and 12.41 ± 4.18 s, respectively). Crosslinking hyaluronic acid with liposomes and crocin significantly increases the permanence and stability of the lipid, aqueous, and mucin tear film layers. In a short-term period, liposome and crosslinked hyaluronic acid achieved better first and mean noninvasive break-up times than standard hyaluronic acid.

Crosslinked Hyaluronic Acid Gels with Blood-Derived Protein Components for Soft Tissue Regeneration.

Hyaluronic acid (HA) is an ideal initial material for preparing hydrogels, which may be used as scaffolds in soft tissue engineering based on their advantageous physical and biological properties. In this study, two crosslinking agents, divinyl sulfone (DVS) and butanediol diglycidyl ether, were used to investigate their effect on the properties of HA hydrogels. As HA hydrogels alone do not promote cell adhesion on the scaffold, fibrin and serum from platelet-rich fibrin (SPRF) were combined with the scaffold; the aim was to create a material intended to be used as soft tissue implant that facilitates new tissue formation, and degrades over time. The chemical changes were characterized and cell attachment capacity of the protein-containing gels was examined using human mesenchymal stem cells, and viability was assessed using live-dead staining. Fourier-transform infrared measurements revealed that linking fibrin into the gel was more effective than linking SPRF. The scaffolds were found to be able to support cell adherence onto the hydrogels, and the best result was achieved when HA was crosslinked with DVS and contained fibrin. The most promising derivative, 5% DVS-crosslinked fibrin-containing hydrogel, was injected subcutaneously into C57BL/6 mice for 12 weeks. The scaffold was proven to be biocompatible, remodeling, and vascularization occurred, while shape and integrity were maintained. Impact statement Fibrin was combined with crosslinked hyaluronic acid (HA) for regenerative application, the structure of the combination of crosslinked HA with blood-derived protein was analyzed and effective coating was proven. It was observed that the fibrin content led to better mesenchymal stem cell attachment in vitro. The compositions showed biocompatibility, connective tissue and vascularization took place when implanted in vivo. Thus, a biocompatible, injectable gel was produced, which is a potential candidate for soft tissue implantation.

Evaluation of the Volumizing Performance of a New Volumizer Filler in Volunteers with Age-Related Midfacial Volume Defects.

PURPOSE: The primary aim of this study was to evaluate the performance of the study product, in terms of volumizing activity as well as the duration of the effect, in women with age-related midfacial volume defects. In addition, the study allowed the evaluation of the tolerability of the product by both volunteers and investigators. PATIENTS AND METHODS: Twenty-two female volunteers, aged 42-60 years, participated in this study, which was performed under dermatological control in a single center. After an initial visit at baseline to verify adherence to the protocol criteria, volunteers received an injection of Aliaxin® SV (IBSA Farmaceutici Italia Srl), followed 3-4 weeks later by a second touch-up treatment to treat eventual asymmetries. Four subsequent visits, the last performed 9 months from the first injection, were performed to evaluate clinically and instrumentally the efficacy of the treatment. RESULTS: Clinical and statistically significant improvement in cheek volume was recorded after the first postinjection visit, and the effect was maintained until the end of the study period. A clinically measurable amelioration of wrinkle severity was also observed. By 3D picture recording and subsequent quantitative analysis, it was possible to determine the efficacy in terms of increased facial volume, which was already appreciable at the first visit, was further increased at the second and third visits and was maintained at the fourth and last visits. The injections were very well tolerated by the volunteers, as determined by their self-evaluation questionnaires. CONCLUSION: The results of the study confirm the esthetic performance of the study product on age-related midfacial volume defects. The very strong high-volumizing activity of the study product was not only properly determined by the investigators but also confirmed by self-evaluation by the volunteers. These effects were obtained with no appreciable undesired effects.

Crosslinked hyaluronic acid with liposomes and crocin for management symptoms of dry eye disease caused by moderate meibomian gland dysfunction.

AIM: To study the effect of uncrosslinked and crosslinked hyaluronic acid combined with other artificial tear components in patients with dry eye caused by moderate meibomian gland dysfunction. METHODS: Prospective, single-blind, contralateral eye study. Fifty eyes (25 patients) were analyzed. Eye selection for each tear type was random, and the eye drop formulations, 0.4% uncrosslinked hyaluronic acid and 0.2% galactoxyloglucan (tear A) and 0.15% crosslinked hyaluronic acid, crocin, and liposomes (tear B) were used. The determined dosing schedule was three times a day for six weeks, and the study participants underwent a clinical examination before and 45d after lubricant treatment. The Schirmer test, tear breakup time (TBUT) test, and Ocular Surface Disease Index (OSDI) questionnaire were applied before and after instillation period with both types of artificial tears. RESULTS: On the Schirmer test, a significant improvement was obtained with both tear A (P<0.01) and tear B (P<0.01). On the TBUT test, a significant improvement was obtained with tear A (P<0.01) and tear B (P<0.01). The OSDI score significantly decreased after instillation period with both artificial tear types (P<0.01). CONCLUSION: Uncrosslinked hyaluronic acid combined with other components, such as tamarind seed polysaccharide, and crosslinked hyaluronic acid combined with liposomes and crocin are effective for management symptoms of dry eye disease.

Efficacy of eye drops containing crosslinked hyaluronic acid and CoQ10 in restoring ocular health exposed to chlorinated water.

PURPOSE: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water. METHODS: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5). RESULTS: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (-3.00 s) (p = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining (p < 0.0001), Ocular Surface Disease Index (p < 0.05), and visual analog scale (p = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent. CONCLUSION: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL®, has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.

Association of Platelet-Rich Plasma and Auto-Crosslinked Hyaluronic Acid Microparticles: Approach for Orthopedic Application.

Platelet-rich plasma (PRP) associated with high molecular weight hyaluronic acid (HA) has been clinically used for tissue regeneration in orthopedics. Despite the recognized beneficial clinical outcomes (e.g., early pain control, improvement of patients' functional limitation and longer-term effectiveness compared to PRP and HA alone in mild and moderate osteoarthritis treatments), its use is still challenging and controversial due to lack of standardization of association practical protocols. Moreover, most studies neglect the matrix structure, that generates the ultimate properties of the association among platelets, fibrin network and the microparticles. In the present work, we aimed to analyze the influence of the PRP/HA association with a controlled matrix structure on the stability, rheological behavior, release of growth factors and in vitro proliferation of human adipose-derived mesenchymal cells (h-AdMSCs). The attenuation of the negative charge of HA was also evaluated. Pure PRP (P-PRP) (i.e., plasma enriched with platelets and poor in leukocytes) was prepared by centrifugation and activated with serum and calcium chloride (AP-PRP). Autocrosslinked hyaluronic acid (AHA) was prepared by organocatalyzed auto-esterification and structured in microparticles (MPAHA) by shearing. The attenuation of the negative charge of MPAHA was performed with chitosan (CHT) by polyelectrolyte complexation yielding MPAHA-CHT. The results showed that microparticles (MPs) have viscoelastic properties, extrusion force and swelling ratio appropriate for injectable applications. The association of AP-PRP with the controlled structure of MPAHA and MPAHA-CHT formed a matrix composed of platelets and of a fibrin network with fibers around 160 nm located preferably on the surface of the MPs with an average diameter of 250 µm. Moreover, AP-PRP/MPAHA and AP-PRP/MPAHA-CHT associations were non-toxic and supported controlled growth factor (PDGF-AB and TGF-ß1) release and in vitro proliferation of h-AdMSC with a similar pattern to that of AP-PRP alone. The best h-AdMSC proliferation was obtained with the AP-PRP/MPAHA-CHT75:25 indicating that the charge attenuation improved the cell proliferation. Thus, the association of AP-PRP with the controlled structure of HA can be a valuable approach for orthopedic applications.

Co-Spray-Dried Urea Cross-Linked Hyaluronic Acid and Sodium Ascorbyl Phosphate as Novel Inhalable Dry Powder Formulation.

The pathogenesis and progression of several lung disorders is propagated by inflammatory and oxidative processes, which can be controlled by adjunctive inhaled therapies. The present study aimed to develop an inhalable dry powder formulation consisting of co-spray-dried urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate (SD HA-CL-SAP), a novel combination which was recently shown to possess anti-inflammatory, antioxidant, and wound healing properties. Native HA and SAP were co-spray dried (SD HA-SAP) and evaluated as control formulation. Yield (Y%) and encapsulation efficiency (EE%) were 67.0 ± 4.8% and 75.5 ± 7.2% for SD HA-SAP, 70.0 ± 1.5% and 66.5 ± 5.7% for SD HA-CL-SAP, respectively. Both formulations were shown to be suitable for lung delivery in terms of morphology, particle size (median volumetric diameter ∼ 3.4 µm), physical and thermal stability, in vitro aerosol performance - respirable fraction: 30.5 ± 0.7% for SD HA-SAP and 35.3 ± 0.3% for SD HA-CL-SAP. SAP release was investigated using Franz cells and air-interface Calu-3 cell model (>90% of SAP transported within 4 h). The innovative SD HA-CL-SAP formulation holds potential as inhalable dry powder for the treatment of inflammatory lung disorders.

In vitro characterization of physico-chemical properties, cytotoxicity, bioactivity of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate nasal powder formulation.

An innovative lyophilized dry powder formulation consisting of urea-crosslinked hyaluronic acid (HA-CL) and sodium ascorbyl phosphate (SAP) - LYO HA-CL - SAP- was prepared and characterized in vitro for physico-chemical and biological properties. The aim was to understand if LYO HA-CL - SAP could be used as adjuvant treatment for nasal inflammatory diseases. LYO HA-CL - SAP was suitable for nasal delivery and showed to be not toxic on human nasal septum carcinoma-derived cells (RPMI 2650 cells) at the investigated concentrations. It displayed porous, polygonal particles with unimodal, narrow size distribution, mean geometric diameter of 328.3 ±â€¯27.5 µm, that is appropriate for nasal deposition with no respirable fraction and 88.7% of particles with aerodynamic diameter >14.1 µm. Additionally, the formulation showed wound healing ability on RPMI 2650 cells, and reduced interleukin-8 (IL-8) level in primary nasal epithelial cells pre-induced with lipopolysaccharide (LPS). Transport study across RPMI 2650 cells showed that HA-CL could act not only as carrier for SAP and active ingredient itself, but potentially also as mucoadhesive agent. In conclusion, these results suggest that HA-CL and SAP had anti-inflammatory activity and acted in combination to accelerate wound healing. Therefore, LYO HA-CL - SAP could be a potential adjuvant in nasal anti-inflammatory formulations.

Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye.

PURPOSE: Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). METHODS: Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. RESULTS: At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. CONCLUSIONS: The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

Combination of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate for the treatment of inflammatory lung diseases: An in vitro study.

This in vitro study evaluated, for the first time, the safety and the biological activity of a novel urea-crosslinked hyaluronic acid component and sodium ascorbyl phosphate (HA-CL - SAP), singularly and/or in combination, intended for the treatment of inflammatory lung diseases. The aim was to understand if the combination HA-CL - SAP had an enhanced activity with respect to the combination native hyaluronic acid (HA) - SAP and the single SAP, HA and HA-CL components. Sample solutions displayed pH, osmolality and viscosity values suitable for lung delivery and showed to be not toxic on epithelial Calu-3 cells at the concentrations used in this study. The HA-CL - SAP displayed the most significant reduction in interleukin-6 (IL-6) and reactive oxygen species (ROS) levels, due to the combined action of HA-CL and SAP. Moreover, this combination showed improved cellular healing (wound closure) with respect to HA - SAP, SAP and HA, although at a lower rate than HA-CL alone. These preliminary results showed that the combination HA-CL - SAP could be suitable to reduce inflammation and oxidative stress in lung disorders like acute respiratory distress syndrome, asthma, emphysema and chronic obstructive pulmonary disease, where inflammation is prominent.

Formulation and Characterization of Native and Crosslinked Hyaluronic Acid Microspheres for Dermal Delivery of Sodium Ascorbyl Phosphate: A Comparative Study.

The present work evaluates for the first time the use of urea-crosslinked hyaluronic acid (HA-CL), a novel derivative of native hyaluronic acid (HA), to produce microspheres (MS) by emulsification-solvent evaporation, for dermal delivery of sodium ascorbyl phosphate (SAP). As the term of comparison, HA MS were prepared. A pre-formulation study-investigation of the effects of polymers solutions properties (pH, viscosity) and working conditions-led to the - production of optimized HA-CL MS and HA-CL-SAP MS with: almost unimodal size distributions; mean diameter of 13.0 ± 0.7 and 9.9 ± 0.8 µm, respectively; spherical shape and rough surface; high yield, similar to HA MS and HA⁻SAP MS (≈ 85%). SAP was more efficiently encapsulated into HA-CL MS (78.8 ± 2.6%) compared to HA MS (69.7 ± 4.6%). Physical state, thermal properties, relative moisture stability of HA-CL MS and HA-CL⁻SAP MS were comparable to those of HA MS and HA⁻SAP MS. However, HA-CL⁻SAP MS exhibited an extended drug release compared to HA⁻SAP MS, despite the same kinetic mechanism-contemporaneous drug diffusion and polymer swelling/dissolution. Therefore, HA-CL formulation showed a greater potential as microcarrier (for encapsulation efficiency and release kinetic), that could be improved, in future, using suitable excipients.