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.

Enhancement of oral bioavailability of drugs using lipid-based carriers: a meta-analysis study.

Cancer is the disease of this era. Its therapy is moving through ups and downs not only due to poor effectiveness of many treating drugs, but also due to the serious side effects always evolving. In an attempt to overcome this problem, many systems, including lipid-based carriers, have been exploited for their oral delivery. Throughout this study, the meta-analysis tool was used to combine data from different studies and extract evidences that lipid-based carriers enhance the oral bioavailability. Consequently, increasing the efficiency and the reduction in side effects of drugs would follow. Accordingly, the usual parameter to indicate the bioavailability; the area under effect curve (AUC) was used where the lipid carriers have proven their superiority over conventional formulations. Interestingly, by comparing microemulsion/self-microemulsifying system (SMEDDS) versus liposomes/pro-liposomes as subgroups of the meta-analysis study, insignificant differences were recorded between them.

Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication.

Glaucoma treatment with ocular medications requires overcoming the corneal barrier to drug penetration. Liposomes have a great corneal penetration ability and affinity while suffering from poor stability and low entrapment of hydrophilic drugs accompanied by rapid drug release. This work aims to develop a new, effective and stable glaucoma medication with sustained drug release properties; Timolol maleate gelatinized core liposomes. A full factorial design was utilized to study the effects of three formulation variables on drug loading and vesicle particle size. Vesicles were prepared by the thin-film hydration method, and characterized for in-vitro drug release and stability. Intra-ocular pressure (IOP) reduction was evaluated in-vivo on glaucomatous rabbit's eyes. The safety profile was assessed using histopathological examinations. Gelatin significantly increased the drug entrapment percentage reaching 50% with a particle size of 38.81 µm. Sustained drug release was recorded compared to a marketed product and to a conventional liposomal formulation. The prepared vesicles caused the highest reduction in IOP accompanied by safe histological findings. This work provided a new, safe and effective ocular glaucoma medication; Timolol maleate gelatinized core liposomes, solving the main problems of ocular liposomal formulations of hydrophilic drugs, suitable for the pharmaceutical industry and comprising abundant and relatively cheap components.