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Despite the high success rates of dental implants, peri-implantitis is currently the most common complication in dental implantology. Peri-implantitis has an inflammatory nature, it is associated with the accumulation of plaque in the peri-implant tissues, and its evolution can be progressive depending on various factors, comorbidities, and poor oral health. Prophylaxis and different treatment methods have been widely discussed in recent decades, and surgical and non-surgical techniques present both advantages and disadvantages. In this work, a literature review of different studies on the application of adjuvant treatments, such as local and systemic antibiotics and antiseptic treatments, was conducted. Positive outcomes have been found in the short (up to one year after treatment) and long term (up to ten years after treatment) with combined therapies. However, there is still a need to explore new therapies based on the use of advanced drug delivery systems for the effective treatment of peri-implantitis in the long term and without relapses. Hence, micro- and nanoparticles, implants, and injectable hydrogels, among others, should be considered in future peri-implantitis treatment with the aim of enhancing overall therapy outcomes.

Anti-vascular endothelial growth factor drugs keep being the main therapy for neovascular age-related macular degeneration (AMD). Possible predictive parameters (demographic, biochemical and/or inflammatory) could anticipate short-term treatment response with ranibizumab. 46 treatment-naive patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD and the clinical examination was made at baseline and one month after the third injection. Demographic characteristics, co-morbidities and concomitant treatments were recorded at the baseline visit. Biochemical parameters, complete blood count and inflammation biomarkers were also measured at these times. Uric Acid was found to be statistically significant with a one-point difference between good and poor responders in both basal and treated patients, but only in basal parameters was statistical significance reached (p = 0.007 vs. p = 0.071 in treated patients). Cholesterol and inflammatory parameters such as white blood cell count and neutrophils were significantly reduced over time when treated with intravitreal ranibizumab. On the other hand, women seemed to have a worse prognosis for short-term response to intravitreal ranibizumab treatment. Uric acid may help identify possible non-responders before initial treatment with ranibizumab, and cholesterol and white blood cells could be good candidates to monitor short-term response to ranibizumab treatment.

Background: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. Methods: Long-term stability at −20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. Results: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. Conclusions: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at −20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Fungal keratitis (FK) is a corneal mycotic infection that can lead to vision loss. Furthermore, the severity of FK is aggravated by the emergence of resistant fungal species. There is currently only one FDA-approved formulation for FK treatment forcing hospital pharmacy departments to reformulate intravenous drug preparations with unknown ocular bioavailability and toxicity. In the present study, natamycin/voriconazole formulations were developed and characterized to improve natamycin solubility, permanence, and safety. The solubility of natamycin was studied in the presence of two cyclodextrins: HPβCD and HPγCD. The HPβCD was chosen based on the solubility results. Natamycin/cyclodextrin (HPβCD) inclusion complexes characterization and a competition study between natamycin and voriconazole were conducted by NMR (Nuclear Magnetic Resonance). Based on these results, several eye drops with different polymer compositions were developed and subsequently characterized. Permeability studies suggested that the formulations improved the passage of natamycin through the cornea compared to the commercial formulation Natacyn®. The ocular safety of the formulations was determined by BCOP and HET-CAM. The antifungal activity assay demonstrated the ability of our formulations to inhibit the in vitro growth of different fungal species. All these results concluded that the formulations developed in the present study could significantly improve the treatment of FK.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at −20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at −20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs. Although renal damage prevails during initial stages, the deposition of cystine crystals in the cornea causes severe ocular manifestations. At present, cysteamine is the only topical effective treatment for ocular cystinosis. The lack of investment by the pharmaceutical industry, together with the limited stability of cysteamine, make it available only as two marketed presentations (Cystaran® and Cystadrops®) and as compounding formulations prepared in pharmacy departments. Even so, new drug delivery systems (DDSs) need to be developed, allowing more comfortable dosage schedules that favor patient adherence. In the last decades, different research groups have focused on the development of hydrogels, nanowafers and contact lenses, allowing a sustained cysteamine release. In parallel, different determination methods and strategies to increase the stability of the formulations have also been developed. This comprehensive review aims to compile all the challenges and advances related to new cysteamine DDSs, analytical determination methods, and possible future therapeutic alternatives for treating cystinosis.

A new cyclodextrin polypseudorotaxanes nail lacquer (Regenail®) containing biotin, methyl sulphonyl methane (MSM), and dimethylsilanediol salicylate was developed and evaluated in vitro and in vivo. The product was developed to improve nail status and diminish signs of pathological nail alterations. A reference product (Betalfatrus®) was used for comparative purposes. An in vitro permeation experiment in hooves showed high MSM and biotin absorption. The content of sulfur and silicon in hooves was also found to be higher compared with the reference product. MSM was tested in human keratinocytes, exhibiting a good cytotoxicity profile and anti-inflammatory activity by the reduction in IL-8 and TNF-α under LPS stimuli. A clinical study was performed to check product safety and efficacy against nail brittleness and alterations such as Beau’s lines and onychorrhexis. A reduction in both alterations and in surface roughness without alteration of nail structure was observed, with a good level of patient acceptance and satisfaction.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are two techniques used in the resection of gastrointestinal mucosal polyps. The aim of this work is the development and evaluation of an innovative polymeric solution containing sodium carboxymethylcellulose and hyaluronic acid. For this purpose, several mixtures of these two main components, as well as other components such as fructose, citric acid, and zinc, are evaluated in terms of physicochemical and microbiological properties, rheological behavior, extensibility, syringeability, and stability at different storage conditions. Furthermore, the potential production of mucosal elevation and duration is also studied by an ex vivo model using porcine stomach and colon. Results show that the developed polymeric solutions possess optimal values of pH, from 4.58 to 6.63, for their use in the gastrointestinal tract. The formulations exhibit both Newtonian and pseudoplastic behaviors with different viscosity values as a function of their composition. All formulations exhibit high stability properties and no bacterial or fungal growth is detected. MCS01 and MCS05 are the polymeric solutions with the best syringeability results. In this line, MCS05 is the formulation that provides the highest, 2.20 ± 0.18 cm and 1.40 ± 0.11 cm, and longest-lasting, for more than 120 min, elevation effect on porcine submucosal stomach and colon tissues, respectively. Thus, it can be concluded that polymeric solution MCS05 might be considered as a promising tool for use in human EMR and ESD.

Cyclodextrin/poloxamer-soluble polypseudorotaxane-based nail lacquers have demonstrated significant capacity for promoting the permeation of drugs into the nail plate. Furthermore, previous studies have shown that the use of hydroalcoholic blends as vehicles promotes drug permeation. The work described herein studies the effect of the type of alcohol used in the lacquer preparation, and the composition of the vehicle is optimized to obtain soluble doses of 8% and to promote the diffusion of ciclopirox base and olamine across the nail. Permeation studies on different types of alcohols show that optimum results are achieved with short-chain alcohols, and that results become less satisfactory the higher the number of alcohol carbons. In addition, solubility and penetration studies on the bovine hoof have enabled the composition of the lacquer to be optimized for both forms of ciclopirox. The results suggest that optimized lacquers have better ciclopirox diffusion and penetration properties than the commercial reference lacquer. Lastly, in vivo studies in which optimized ciclopirox olamine lacquer was applied for 45 days to the nails of healthy volunteers showed that it caused no negative effects or changes to the nail surface. These results demonstrate the significant potential of cyclodextrin/poloxamer-soluble polypseudorotaxane-based nail lacquers for the ungual administration of drugs.

Mucopolysaccharidosis IVA (Morquio A) is a rare inherited metabolic disease caused by deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS). Until now, treatments employed included hematopoietic stem cell transplantation and enzyme replacement therapy (ERT); the latter being the most commonly used to treat mucopolysaccharidoses, but with serious disadvantages due to rapid degradation and clearance. The purpose of this study was to develop and evaluate the potential of nanostructured lipid carriers (NLCs) by encapsulating elosulfase alfa and preserving its enzyme activity, leading to enhancement of its biological effect in chondrocyte cells. A pegylated elosulfase alfa-loaded NLC was characterized in terms of size, ζ potential, structural lipid composition (DSC and XRD), morphology (TEM microscopy), and stability in human plasma. The final formulation was freeze-dried by selecting the appropriate cryoprotective agent. Viability assays confirmed that NLCs were non-cytotoxic to human fibroblasts. Imaging techniques (confocal and TEM) were used to assess the cellular uptake of NLCs loaded with elosulfase alfa. This study provides evidence that the encapsulated drug exhibits enzyme activity inside the cells. Overall, this study provides a new approach regarding NLCs as a promising delivery system for the encapsulation of elosulfase alfa or other enzymes and the preservation of its activity and stability to be used in enzymatic replacement therapy (ERT).

Intravitreal administration of anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for Age-Related Macular Degeneration; however, the knowledge of their pharmacokinetics is limited. A comprehensive review of the preclinical and clinical pharmacokinetic data that were obtained in different studies with intravitreal bevacizumab, ranibizumab, and aflibercept has been conducted. Moreover, the factors that can influence the vitreous pharmacokinetics of these drugs, as well as the methods that were used in the studies for analytical determination, have been exposed. These anti-VEGF drugs present different charge and molecular weights, which play an important role in vitreous distribution and elimination. The pharmacokinetic parameters that were collected differ depending on the species that were involved in the studies and on physiological and pathological conditions, such as vitrectomy and lensectomy. Knowledge of the intravitreal pharmacokinetics of the anti-VEGF drugs that were used in clinical practice is of vital importance.

Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.

Onychomycosis affects about 15% of the population. This disease causes physical and psychosocial discomfort to infected patients. Topical treatment (creams, solutions, gels, colloidal carriers, and nail lacquers) is usually the most commonly required due to the high toxicity of oral drugs. Currently, the most common topical formulations (creams and lotions) present a low drug delivery to the nail infection. Nail lacquers appear to increase drug delivery and simultaneously improve the effectiveness of treatment with increased patient compliance. These formulations leave a polymer film on the nail plate after solvent evaporation. The duration of the film residence in the nail constitutes an important property of nail lacquer formulation. In this study, a polyurethane polymer was used to delivery antifungals drugs, such as terbinafine hydrochloride (TH) and ciclopirox olamine (CPX) and the influence of its concentration on the properties of nail lacquer formulations was assessed. The nail lacquer containing the lowest polymer concentration (10%) was the most effective regarding the in vitro release, permeation, and antifungal activity. It has also been demonstrated that the application of PU-based nail lacquer improves the nail plate, making it smooth and uniform and reduces the porosity contributing to the greater effectiveness of these vehicles. To conclude, the use of polyurethane in nail formulations is promising for nail therapeutics.

Nail delivery has interest for local treatment of nail diseases. Nevertheless, the low permeability of drugs in the nail plaque precludes the efficacy of local treatments. The use of penetration enhancers can increase drug permeability and improve the efficacy of the treatment of nail pathologies. In this work, different chemical substances have been evaluated as potential penetration enhancers. With this aim, the effect of different substances such as sodium lauryl sulfate (SLS), polyethylene glycol 300 (PEG 300), carbocysteine, N-acetylcysteine, lactic acid, potassium phosphate, Labrasol® and Labrafil® in the microstructure, nail surface and drug permeability has been evaluated. The models obtained by mercury intrusion porosimetry and PoreXpert™ software show a more porous structure in nails treated with different enhancers. Permeation studies with bovine hooves and nails revealed that all the hydroalcoholic lacquers developed, and particularly those prepared with SLS, provide better nail penetration of the drugs ciclopirox olamine and clobetasol propionate. Results have shown that the increase of the drug penetration in the nail is caused by the formation of a porous random microstructure and by the decrease of the contact angle between lacquers and the surface or the nail plaque. The presence of SLS produces an improvement in the spreading of the solution on the nail surface and promotes the penetration of the solution into the nail pores. The hydroalcoholic lacquer, elaborated with cyclodextrin/poloxamer soluble polypseudorotaxane and sodium lauryl sulfate as an enhancer, allowed the rate of diffusion and penetration of the active ingredient within the nail to be significantly higher than obtained with the reference lacquers when using either ciclopirox olamine or clobetasol propionate as the active ingredient.