Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies.

Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98-16.56 folds on MCF-7 and CaCo2 cells and 47.82-98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5-1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer.

Therapeutic potential of limonene-based syringic acid nanoemulsion: Enhanced ex-vivo cutaneous deposition and clinical anti-psoriatic efficacy.

Nanoemulsions have carved their position in topical delivery owing to their peculiar features of forming a uniform film on the skin and conquering stratum corneum barrier and hence fostering dermal penetration and retention. The present work developed syringic acid nanoemulsion (SA-NE) by spontaneous emulsification as an anti-psoriatic remedy via the dermal route. SA-NE were prepared with either lauroglycol90, limonene or their combination (oil phase) and tween80 (surfactant) with variable concentrations. The physicochemical characteristics of SA-NE were assessed together with Ex-vivo skin deposition and dermal toxicity. The effectiveness of optimal formula in psoriatic animal model and psoriatic patients was investigated using PASI scoring and dermoscope examination. Results showed that, SA-NE containing mixture of lauroglycol 90, limonene and 10 % tween80 (F5), was selected as the optimal formula presenting stable nanoemulsion for 2-month period, showing droplet size of 177.6 ± 13.23 nm, polydispersity index of 0.16 ± 0.06, zeta potential of -21.23 ± 0.41 mV. High SA% in different skin strata and no dermal irritation was noticed with limonene-based SA-NE also it showed high in-vitro anti- inflammatory potential compared to the blank and control formulations. A preclinical study demonstrated that limonene-based SA-NE is effective in alleviating psoriasis-like skin lesions against imiquimod-induced psoriasis in rats. Clinically, promising anti-psoriatic potential was asserted as all patients receiving F5 experienced better clinical improvement and response to therapy, achieving ≥ 50 % reduction in PASI scores versus only 35 % responders in the Dermovate® cream group. Collectively, the practical feasibility of limonene-based SA-NE topical delivery can boost curative functionality in the treatment of psoriatic lesions.

Unraveling the pharmaceutical and clinical relevance of the influence of syringic acid loaded linoleic acid transferosomes on acne.

Natural medicines are promising platforms for competent topical treatment modalities benefiting the cosmetic implementation and proffering solutions to the current remedies. Therefore, the objective of this study was to formulate syringic acid (SA), well-known for its multilateral anti-inflammatory, antimicrobial and antioxidant potentials, in newly developed linoleic acid (LA) transferosomes as an anti-acne nano-form remedy. Herein, LA was incorporated in transferosomes owing to its antimicrobial effect and dermal penetrability. Comprehensive appraisal through physicochemical, antioxidant and dermal deposition investigations was conducted. Clinical assessment was also performed in acne patients and compared with the marketed product (Adapalene® gel). The relevant investigations of the optimum formula indicated stable vesicles with a small-sized diameter (147.46 nm), surface charge (-26.86 mV), spherical architecture, reasonable entrapment (76.63%), considerable antioxidant activity (IC50 = 11.1 µg/mL) and remarkable skin deposition (78.72%).More importantly, LA based transferosomes enclosing SA exhibited inflammation lessening in acne sufferers as manifested by greater reduction in the total count of the acne lesions reaching 79.5% in contrast to Adapalene® gel with only 18.7% reduction in acne lesions. Interestingly, no irritation and erythema were reported for the proposed transferosomes. Inclusively, the cosmetic formulation practice could reap benefits of the development of such vesicles.

"Spanlastic nanovesicles for enhanced ocular delivery of vanillic acid: design, in vitro characterization, and in vivo anti-inflammatory evaluation".

Spanlastics are novel surfactant-based, elastic vesicular nanocarriers composed of spans and edge activators. The present work aims to exploit their special penetration enhancing properties to enhance the ophthalmic delivery of the versatile nutraceutical vanillic acid (VA), for treatment of ocular inflammation. VA-loaded spanlastics were formulated by ethanol injection method using Tween 80, sodium deoxy cholate or Tween 60 as edge activators (EA) at various Span 60: EA mass ratios. Vesicles were characterized for their particle size (PS), polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), surface morphology, in vitro release profile, thermal properties and long-term stability, in addition to in vivo anti-inflammatory efficacy of the selected formula in an endotoxin-induced uveitis model. Selected formulation composed of Span 60: Tween 80 at a mass ratio of 70:30 displayed smallest PS of 299.8 ± 9.97 nm, PDI of 0.386 ± 0.047, an acceptable EE%, as well as good physical stability for 3 months. According to clinical scoring, inflammatory mediators levels and histopathological examination, VA-loaded spanlastic formulation resulted in significant alleviation of inflammation compared to drug suspension (p < 0.05). Formulation of VA into spanlastic nanoformulation is a promising approach to improve its ocular permeability, absorption and anti-inflammatory activity providing a safer alternative to current regimens.

Chitosan nanoparticles making their way to clinical practice: A feasibility study on their topical use for acne treatment.

Despite the popularity of chitosan as a biodegradable polymer used in a variety of applications, clinical trials involving chitosan or its nanoparticles are still scarce. Moreover, the use of nutraceuticals as a replacement to conventional chemical treatments has become currently popular, and if combined with nanotechnology, nutraceuticals can achieve a comparable or even better therapeutic outcome. In the current work, chitosan nanoparticles loading the nutraceutical nicotinamide were optimized, characterized, and clinically tested on patients suffering from acne vulgaris. The topical merits of chitosan nanoparticles were proven, in which they exhibited strong skin adhesion ex vivo and high nicotinamide deposition in the different skin layers (stratum corneum, epidermis and dermis) amounting to a total of 68%. When clinically tested on patients, nicotinamide nanoparticles displayed 73% reduction in the inflammatory acne lesions compared to untreated areas, hence proving that chitosan nanoparticles can be a clinically sounding option for treatment of skin diseases.