Topical Treatment for Retinal Degenerative Pathologies: A Systematic Review.

The topical administration of medicines is the preferred route in ocular therapy, at least for the anterior segment of the eye. However, the eye's inherent functional and biological barriers all work against the active pharmaceutical ingredient (API) to efficiently reach the targeted retinal structures. The main objective of this article is to offer a systematic review of the scientific literature in recent years, focusing on the latest developments of topical treatment intended for retinal degenerative diseases. Database search returned 102 clinical studies, focused on topical treatment for age macular degeneration, macular edemas (in diabetic retinopathy, surgery related or in retinal dystrophies) or glaucoma. After the exclusion of low-powered studies and those combining vitreo-retinal surgery, 35 articles remained for analysis. Currently, the topical treatment of retinal degenerative diseases is limited by the difficulty to deliver effective drug concentrations to the posterior eye structures. However, in the case of drug classes like NSAIDs, the presence of certain molecular and metabolic features for specific representatives makes the topical administration currently feasible in several clinical contexts. For other drug classes, either a fine-tuning of the API's pharmacokinetic profile or the use of more advanced formulation strategies, such as rationally designed nanostructured drugs and vehicles, crystalline polymorphs or supramolecular complexes, could bring the much awaited breakthrough for a more predictable and controlled delivery towards the retinal structures and could eventually be employed in the future for the development of more effective ways of delivering drugs to the posterior eye, with the ultimate goal of improving their clinical efficacy.

Optimization of a Mucoadhesive Vaginal Gel Containing Clotrimazole Using a D-Optimal Experimental Design and Multivariate Analysis.

The aim of this study was to develop a suitable clotrimazole (CLT)-loaded mucoadhesive vaginal gel (CLT-MVG) for topical applications in vaginal candidiasis. Ten CLT-MVG formulations were prepared, consisting of mixtures of acid polyacrylic (Carbopol 940) and polyethene oxides, Sentry Polyox WSRN 1105 or 750, according to an experimental D-optimal design, and CLT was suspended at a ratio of 1%. The prepared CLT-MVG formulations were studied in vitro, and the formulation containing Carbopol 940 0.89% combined with PEO 1105 1.39% was identified with the optimal rheological and in vitro bioadhesion properties, ensuring the prolonged release of CLT, with a similarity factor greater than 50, indicating dissolution profile similarity for three batches of the optimized formulation. This optimized formulation showed a pH in the tolerance range, and an adequate ex vivo mucoadhesion time, while the FT-IR studies revealed no interactions between the excipients and CLT. The microscopic analysis identified a mean particle size of suspended CLT of 5.24 ± 0.57 µm. The in vitro antifungal activity of the optimized formulation was tested on twenty strains of Candida albicans and proved to be better compared to a marketed clotrimazole preparation, showing a greater inhibition effect (p < 0.05). The optimized formulation could be a good candidate for the local treatment of vaginal mycosis.

In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with Doxycycline Hyclate for Topical Application in Periodontitis.

Mucoadhesive films loaded with doxycycline hyclate (Doxy Hyc), consisting of mixtures of hydroxypropylmethyl cellulose (HPMC) E3, K4 and polyacrylic acid (Carbopol 940), were prepared by casting method, aiming to design a formulation intended for application in the oral cavity. The obtained film formulations exhibited a Doxy Hyc content between 7.52 ± 0.42 and 7.83 ± 0.41%, which had adequate mechanical properties for application in the oral cavity and pH values in the tolerance range. The x-ray diffraction studies highlighted the amorphisation of Doxy Hyc in the preparation process and the antibiotic particles present on the surface of the films, identified in the TEM images, which ensured a burst release effect in the first 15 min of the in vitro dissolution studies, after which Doxy Hyc was released by diffusion, the data presenting a good correlation with the Peppas model, n < 0.5. The formulation F1, consisting of HPMC K4 combined with C940 in a ratio of 5:3, the most performing in vitro, was tested in vivo in experimentally-induced periodontitis and demonstrated its effectiveness in improving the clinical parameters and reducing the salivary levels of matrix metalloproteinase-8 (MMP-8). The prepared Doxy Hyc loaded mucoadhesive buccal film could be used as an adjuvant for the local treatment of periodontitis, ensuring prolonged release of the antibiotic after topical application.

Immunomodulatory Effect of Novel Electrospun Nanofibers Loaded with Doxycycline as an Adjuvant Treatment in Periodontitis.

The immunomodulatory effect of a novel biomaterial obtained through electrospinning, based on polylactic acid (PLA) and nano-hydroxyapatite (nano-HAP), loaded with doxycycline (doxy) was evaluated in an animal model. The treatment capabilities as a local non-surgical treatment of periodontitis was investigated on the lower incisors of Wistar rats, after the induction of localized periodontitis using the ligature technique. Following the induction of the disease, the non-surgical treatment of scaling and root planing was applied, in conjunction with the application of the new material. The results of the treatment were evaluated clinically, using the tooth mobility and gingival index scores, as well as histologically. The salivary concentrations of matrix metalloproteinase 8 (MMP-8) and plasmatic concentrations of interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also monitored. Two weeks after the ligature application, the periodontal disease was successfully induced in rats. The application of the novel biomaterial obtained through electrospinning was proven to be more effective in improving the clinical parameters, while decreasing the salivary MMP-8 and plasmatic IL-1 and TNF-α concentrations, compared to the simple scaling and root planing. Thus, the novel electrospun biomaterial could be a strong candidate as an adjuvant to the non-surgical periodontal therapy.

In Vitro Antimicrobial Effect of Novel Electrospun Polylactic Acid/Hydroxyapatite Nanofibres Loaded with Doxycycline.

The present study aimed to assess the in vitro antimicrobial effects of a novel biomaterial containing polylactic acid (PLA), nano-hydroxyapatite (nano-HAP) and Doxycycline (Doxy) obtained by electrospinning and designed for the non-surgical periodontal treatment. The antimicrobial activity of two samples (test sample, PLA-HAP-Doxy7: 5% PLA, nano-HAP, 7% Doxy and control sample, PLA-HAP: 5% PLA, nano-HAP) against two periodontal pathogens­Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis­was assessed using the Kirby−Bauer Disk Diffusion Susceptibility Test and compared with the effect of four antibiotics used as adjuvants in periodontal therapy: Amoxicillin, Ampicillin, Doxy and Metronidazole. The test sample (embedded with Doxy) showed higher inhibitory effects than commonly used antibiotics used in the treatment of periodontitis, while the control sample showed no inhibitory effects. Moreover, significant differences were observed between the inhibition zones of the two samples (p < 0.05). The Doxy-loaded PLA nanofibres had an antimicrobial effect against the periodontal pathogens. Based on these results, the novel biomaterial could be a promising candidate as adjuvant for the non-surgical local treatment in periodontitis.

Perspectives of Molecularly Imprinted Polymer-Based Drug Delivery Systems in Ocular Therapy.

Although the human eye is an easily accessible sensory organ, it remains a challenge for drug administration due to the presence of several anatomical and physiological barriers which limit the access of drugs to its internal structures. Molecular imprinting technology may be considered the avant-garde approach in advanced drug delivery applications and, in particular, in ocular therapy. In fact, molecularly imprinted polymers hold the promise to compensate for the current shortcomings of the available arsenal of drug delivery systems intended for ocular therapy. The present manuscript aims to review the recent advances, the current challenges and most importantly to raise awareness on the underexplored potential and future perspectives of molecularly imprinted polymer-based drug delivery systems intended for the treatment of eye diseases.

Topical nanodelivery system of lutein for the prevention of selenite-induced cataract.

Cataracts are responsible for half of the world blindness, surgery being the only viable treatment. Lutein, a naturally occurring carotenoid in the eye, has the potential to reduce cataract progression by protecting the eye from photo-oxidative stress. To restore the eye's natural line of defense against photo-oxidative stress, a formulation was developed using zein and poly(lactic-co-glycolic acid) nanoparticles (NPs) embedded in an optimized bioadhesive thermosensitive gel for the delivery of lutein via topical application. Cataracts were induced in Crl:WI rats via selenite injection at 13 days post-partum, followed by 7 days of treatment with free lutein or lutein-loaded NPs administered orally or topically. Cataract severity was significantly reduced in rats treated with topical applications of lutein-loaded NPs compared to the positive control, while no significant differences were observed in rats treated with other lutein formulations including oral and topically applied free lutein.

The pharmaceutical applications of a biopolymer isolated from Trigonella foenum-graecum seeds: Focus on the freeze-dried matrix forming capacity.

The aim of the present study was to evaluate the funtion of fenugreek seed mucilage (FSM) as potential matrix forming agent for orodispersible pharmaceutical lyophilisates. The FSM was isolated and characterized. FSM colloidal dispersions were prepared and the rheological evaluation was performed. Oral lyophilisates (OLs) with different FSM concentrations, containing meloxicam as model drug were prepared by freeze drying method. The OLs were characterized and compared to gelatin containing tablets, prepared under the same conditions. The FSM dispersions revealed shear thinning flow type. Based on colloidal dispersions' rheological properties, five FSM concentrations were taken forward to the lyophilization step. Completely dry and elegant tablets were obtained. Texture analysis indicated highly porous structures, confirmed by SEM analysis, which explain the fast disintegration properties. All the prepared tablets disintegrated in less than 47 s. The disintegration process was prolonged by the increase in FSM content, due to the high viscosity the polymer creates in aqueous media. FSM tablets presented longer disintegration times, as compared to gelatin tablets, but also higher crushing strength. Considering the fast disintegration and the high crushing strength, FSM is a good candidate as matrix forming agent for fast disintegrating dosage forms or other freeze-dried preparations.

Improved experimental burn model on rabbits.

OBJECTIVE: The goal of our study was to find an easy and suitable skin burn model for rabbits, to identify the temperature and contact time to reach a deep 2nd degree burn, and to find the best wound dressing fixation method. MATERIAL AND METHODS: We used New Zealand male rabbits as experimental models. On a pilot study, with a copper device heated to temperatures between 43-48 Celsius degrees, the burn was inflicted using contact timesof 3, 4, 5, and 7 seconds. The burn depth was evaluated histological. Twenty-four rabbits were used to evaluate four dressing fixation methods: regular dressing with retention bandages; skin stapler; collars and body resin cast. RESULTS: A 2nd degree deep burn was obtained at 43 degrees for 4 seconds. The retention elastic bandages were removed within hours and the skin staplers were removed with teeth leaving wounds on the skin. The collars were more successful but produced superficial neck lesions. The body resin casts were the most successful. CONCLUSIONS: The best contention method was the bpdy resin cast.

[Skin toxicity of sodium lauryl sulfate as evidenced in an animal model]. / Toxicitatea cutanata, a lauril sulfatului de sodiu evidentiata pe model animal.

This study presents the toxic effects of a very known and used compound in pharmaceutical products and from cosmetic market, a detergent (surface-active) anionic. The presented data underlined the effects of an ointment base with sodium lauryl sulfate, with various concentrations of this detergent, respectively: 0.5%, 1% and 3%, in a long term utilization of this, on an animal model with Sprague Dawley rats.