The human eye is a sophisticated organ with distinctive anatomy and physiology that hinders the passage of drugs into targeted ophthalmic sites. Effective topical administration is an interest of scientists for many decades. Their difficult mission is to prolong drug residence time and guarantee an appropriate ocular permeation. Several ocular obstacles oppose effective drug delivery such as precorneal, corneal, and blood-corneal barriers. Routes for ocular delivery include topical, intravitreal, intraocular, juxtascleral, subconjunctival, intracameral, and retrobulbar. More than 95% of marketed products exists in liquid state. However, other products could be in semi-solid (ointments and gels), solid state (powder, insert and lens), or mixed (in situ gel). Nowadays, attractiveness to nanotechnology-based carries is resulted from their capabilities to entrap both hydrophilic and lipophilic drugs, enhance ocular permeability, sustain residence time, improve drug stability, and augment bioavailability. Different in vitro, ex vivo, and in vivo characterization approaches help to predict the outcomes of the constructed nanocarriers. This review aims to clarify anatomy of the eye, various ocular diseases, and obstacles to ocular delivery. Moreover, it studies the advantages and drawbacks of different ocular routes of administration and dosage forms. This review also discusses different nanostructured platforms and their characterization approaches. Strategies to enhance ocular bioavailability are also explained. Finally, recent advances in ocular delivery are described.
Graphical Abstract
The purpose of this manuscript was to develop and optimize Fenticonazole Nitrate (FTN)-loaded novasomes aiming to enhance drug corneal penetration and to improve its antifungal activity. Ethanol injection was used to formulate FTN-loaded novasomes adopting a central composite design. The researched factors were: stearic acid concentration (g%) (A), span 80: drug ratio (B) and cholesterol amount (mg) (C), and their effects on percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and
in vitro
drug release after 8 hours (Q8h) were studied. Numerical optimization by Design-Expert® software was employed to select the optimum formula in respect to highest EE%, ZP (as absolute value), and Q8h >80% and lowest PS and PDI. Additional evaluation of the optimum formula was accomplished by short term stability study, effect of gamma sterilization, determination of Minimal Inhibitory Concentration and
ex vivo
corneal permeation study. The
in vivo
evaluation of the optimum formula was done to ensure its safety via
in vivo
ocular irritancy and
in vivo
corneal tolerance studies. Also, the efficacy was confirmed through
in vivo
corneal uptake study and susceptibility test. The optimum formula with the highest desirability value (0.738) showed EE% (94.31%), PS (197.05 nm), ZP (-66.95 mV) and Q8h (85.33%). It revealed to be safe, with augmented corneal permeation (527.98 µg/cm
2
) that leads to higher antifungal activity. The above results confirmed the validity of novasomes to improve the corneal permeation and antifungal activity of Fenticonazole Nitrate.
Photodynamic therapy (PDT) is regarded as a treatment option for basal cell carcinoma (BCC). The aim of this study is to investigate the efficacy of methylene blue (MB)-based PDT in patients suffering from nodular or ulcerative BCCs. This study is a prospective clinical trial with a 6-months follow-up. The study setting is at the Dermatology Clinic at NILES, Cairo University, Egypt. Seventeen patients complaining of nodular BCC (nBCC) and three patients complaining of ulcerative BCC (uBCC) were taken as samples. Methylene blue, the photosensitizer, was prepared in two different formulas: liposomal-loaded MB (LMB) was prepared and formulated in hydrogel (MB 0.2%) to be used topically alone for treating BCCs <2 cm in diameter or to be combined with intralesional injection (ILI) of free MB 2% aqueous solution for treating BCCs ≥2 cm in diameter. A session was performed every 2 weeks until complete response (CR) of the lesion or for a maximum of six sessions. Clinical assessments of clinical improvement, dermatological photography, monthly follow-up visits for 6 months, and skin biopsy after 3 months of follow-up to confirm the response, recurrence, or both in cases in which the clinical evaluation was ambiguous. Seventeen patients of the 20 completed the study, 11 patients achieved CR with very good cosmetic outcome, photosensitizer tolerance, and minimal reported side effects. MB is a cheap promising alternative photosensitizer for PDT of nBCC.
Facial erythema is one of the most common outpatient complaints in dermatology. There are various causes of facial erythema and several devices are available for its treatment. Pulsed dye laser (PDL) and intense pulsed light (IPL) are the two common light devices used for these conditions. In this review, we evaluated the literature to assess efficacy of IPL versus PDL in facial erythema and telangiectasia. We searched published articles including clinical trials or reviews articles, case series, and case reports. Electronic databases (MEDLINE and PubMed) were searched to retrieve the articles. Reference lists of selected articles were also considered for the review. Articles published in English language until June 2021 were considered for this review.
The aim of this study was to formulate and boost ocular targeting of Fenticonazole Nitrate (FTN)-loaded olaminosomes in order to improve drug corneal permeation and candidiasis treatment. Olaminosomes were formulated by ethanol injection technique applying a central composite design. The independent variables were: span 80 amount (mg) (A), oleylamine concentration (mg%) (B) and oleic acid: drug ratio (C). The dependent responses were: percent entrapment efficiency (EE %), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and
in vitro
drug release after 10 hours (Q10h). Numerical optimization by Design-Expert® software was adopted to select the optimum formula. This formula was chosen based on highest EE %, ZP (as absolute value) and Q10h and lowest PS and PDI. The optimum formula was subjected to further
in vitro
characterization via Differential scanning calorimetry, Transmission electron microscopy, Fourier transform infrared spectroscopy, pH determination, effect of storage, influence of terminal sterilization, detection of Minimal Inhibitory Concentration and
ex vivo
corneal penetration analysis. Safety and antifungal activity of the optimum formula were tested through various
in vivo
studies like ocular irritancy, corneal tolerance, corneal uptake and susceptibility test. The optimum formula with the maximum desirability value (0.972) revealed EE% (84.24%), PS (117.55 nm), ZP (−74.85 mV) and Q10h (91.26%) respectively. The optimum formula demonstrated ocular tolerance with enhanced corneal penetration behavior (428.66 µg/cm
2
) and boosted antifungal activity (56.13%) compared to FTN suspension (174.66 µg/cm
2
and 30.83%). The previous results ensured the ability of olaminosomes to enhance the corneal penetration and antifungal efficacy of Fenticonazole Nitrate.
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