NULL

In nature, enzyme proteins are the responsible catalysts of biochemical processes at the metabolic level. During evolution, gradual adaptation was gained to survive the environmental pressure and to support the retention of the most beneficial function. The level of many natural metabolites is far from satisfying the need of the pharmaceutical market for the production of a pure drug at a cost-effective range. The biosynthetic origin of xanthones in fungi and lichens is exclusively acetate. The scaffold is formed by the condensation of one molecule of acetyl-CoA with seven molecules of malonyl-CoA to yield an octaketide intermediate. l-phenylalanine is converted to cinnamic acid, a step of the general phenylpropanoid pathway, and cinnamoyl-CoA ends up in benzoic acid, which in turn is activated through an adenylate-activating enzyme. The variability in ecological and environmental factors and the need for certain growth conditions, developmental stages for the production of secondary metabolites inspired researchers to explore alternative sources for sustainable productions of bioactive agents.

The aim of this study was to develop orally disintegrating tablets (ODTs) for enalapril maleate (EnM) to facilitate its administration to the elderly or other patients having dysphagia. Compatibility between EnM and various excipients was studied using differential scanning calorimetry. ODTs of EnM were prepared by direct compression of EnM mixtures with various superdisintegrants. The tablets were evaluated for physical properties including drug content, hardness, friability, disintegration time, wetting time, and drug release. The antihypertensive effect of the optimum EnM ODTs was evaluated in vivo in hypertensive rats and compared with commercial EnM formulation. EnM ODTs had satisfactory results in terms of drug content and friability. Tablet wetting and disintegration were fast and dependent on the used superdisintegrant where croscarmellose showed the fastest wetting and disintegration time of ~7 s. EnM release from the tablets was rapid where complete release was obtained in 10–15 min. Selected EnM ODTs rapidly and efficiently reduced the rat’s blood pressure to its normal value within 1 h, compared with 4 h for EnM commercial formulation. These results confirm that EnM ODTs could find application in the management of hypertension in the elderly or other patients having dysphagia.

The aim of this study was to develop orally disintegrating tablets (ODTs) for enalapril maleate (EnM) to facilitate its administration to the elderly or other patients having dysphagia. Compatibility between EnM and various excipients was studied using differential scanning calorimetry. ODTs of EnM were prepared by direct compression of EnM mixtures with various superdisintegrants. The tablets were evaluated for physical properties including drug content, hardness, friability, disintegration time, wetting time, and drug release. The antihypertensive effect of the optimum EnM ODTs was evaluated in vivo in hypertensive rats and compared with commercial EnM formulation. EnM ODTs had satisfactory results in terms of drug content and friability. Tablet wetting and disintegration were fast and dependent on the used superdisintegrant where croscarmellose showed the fastest wetting and disintegration time of ~7 s. EnM release from the tablets was rapid where complete release was obtained in 10–15 min. Selected EnM ODTs rapidly and efficiently reduced the rat’s blood pressure to its normal value within 1 h, compared with 4 h for EnM commercial formulation. These results confirm that EnM ODTs could find application in the management of hypertension in the elderly or other patients having dysphagia.

The delivery of nanoparticles through receptor-mediated cell interactions has nowadays a major attention in the area of drug targeting applications. This specific kind of targeting is mediated by localized receptors impeded into the target site with subsequent drugs internalization. Hence, this type of interaction would diminish side effects and enhance drug delivery efficacy to the target site. Somatostatin receptors (SSTRs) are one type of G protein-coupled receptors, which could be active targeted for various purposes. There are five SSTRs types (SSTR1-5) which are localized at various organs in the body and spread into different tissues. SSTRs could be considered as a promising target to various nanoparticles which is facilitated when nanoparticles are modified through specific ligand or coating to allow better binding. This review discusses the exploration of SSTRs for active targeting of nanoparticles with certain emphasize on their interaction at the cellular level.

Objective: It is difficult to identify the gold nanoparticles (AuNPs) intracellularly due to their non-fluorescent nature. Although gold can quench the fluorescence of any fluorophore, hence it is also difficult to combine gold with a fluorophore such as a semiconductor quantum dots (QDs). The aim of this study was to prepare a single fluorescent stable AuNPs combined with QDs (QDs-Au-NPs) which can be easily detected intracellularly. Methods: QDs-Au-NPs were prepared via a simple one-step process through controlling the spacing between them using polyethylene glycol (PEG) as space linker in the form of PEGylated QDs. Furthermore, the applicability of this system was evaluated after coating the particles with somatostatin citrate, SST, to active target somatostatin receptors (SSTRs), and identification of the internalized particles via confocal laser scanning spectroscopy. Results: The results showed that the produced Au shell has a thickness of 2.0±0.2 nm and QDs-Au-NPs showed the same fluorescence intensity compared to the unmodified QDs. Additionally, a stable monodisperse QDs-Au-NPs coated with SST were prepared after coating with 11-Mercaptoundecanoic acid. Moreover, cellular uptake study in Human Caucasian breast adenocarcinoma cell lines showed that QDs-Au-SST-NPs could be detected easily using the confocal microscope. In addition, they showed a significant (p .05) internalization per cell compared to untreated QDs-Au-NPs as detected by flow cytometry. Conclusion: It could be concluded that the produced QDs-Au-NPs has a strong fluorescence property like QDs which enable them to be easily detected after cells internalization.

Objective: To develop mucoadhesive tablets for the vaginal delivery of progesterone (P4) to overcome its low oral bioavailability resulting from drug hydrophobicity and extensive hepatic metabolism. Methods: The tablets were prepared using mixtures of P4/Pluronic® F-127 solid dispersion and different mucoadhesive polymers. The tablets were evaluated for physical properties, swelling index, mucoadhesive properties and drug release kinetics. P4 pharmacokinetic and pharmacodynamic properties were evaluated in female rabbits and compared with vaginal micronized P4 tablets and intramuscular (IM) P4 injection, respectively. Results: The tablets had satisfactory physical properties and their swelling, in vitro mucoadhesion force and ex vivo mucoadhesion time were dependent on tablet composition. Highest swelling index and mucoadhesion time were detected for tablets containing 20% chitosan-10% alginate mixture. Most tablets exhibited burst release (~25%) during the first 2 h followed by sustained release for ~48 h. In vivo study showed that chitosan-alginate mucoadhesive tablets had ~2-fold higher P4 mean residence time in the blood and 5-fold higher bioavailability compared with oral P4. Further, same tablets showed 2-fold higher myometrium thickness in rabbit uterus compared with IM P4 injection. Conclusions: These results confirm the potential of these mucoadhesive vaginal tablets to enhance P4 efficacy and avoid the side effects associated with IM injection.

Objective: To develop mucoadhesive tablets for the vaginal delivery of progesterone (P4) to overcome its low oral bioavailability resulting from drug hydrophobicity and extensive hepatic metabolism. Methods: The tablets were prepared using mixtures of P4/Pluronic® F-127 solid dispersion and different mucoadhesive polymers. The tablets were evaluated for physical properties, swelling index, mucoadhesive properties and drug release kinetics. P4 pharmacokinetic and pharmacodynamic properties were evaluated in female rabbits and compared with vaginal micronized P4 tablets and intramuscular (IM) P4 injection, respectively. Results: The tablets had satisfactory physical properties and their swelling, in vitro mucoadhesion force and ex vivo mucoadhesion time were dependent on tablet composition. Highest swelling index and mucoadhesion time were detected for tablets containing 20% chitosan-10% alginate mixture. Most tablets exhibited burst release (~25%) during the first 2 h followed by sustained release for ~48 h. In vivo study showed that chitosan-alginate mucoadhesive tablets had ~2-fold higher P4 mean residence time in the blood and 5-fold higher bioavailability compared with oral P4. Further, same tablets showed 2-fold higher myometrium thickness in rabbit uterus compared with IM P4 injection. Conclusions: These results confirm the potential of these mucoadhesive vaginal tablets to enhance P4 efficacy and avoid the side effects associated with IM injection.

Objective: To develop mucoadhesive tablets for the vaginal delivery of progesterone (P4) to overcome its low oral bioavailability resulting from drug hydrophobicity and extensive hepatic metabolism. Methods: The tablets were prepared using mixtures of P4/Pluronic® F-127 solid dispersion and different mucoadhesive polymers. The tablets were evaluated for physical properties, swelling index, mucoadhesive properties and drug release kinetics. P4 pharmacokinetic and pharmacodynamic properties were evaluated in female rabbits and compared with vaginal micronized P4 tablets and intramuscular (IM) P4 injection, respectively. Results: The tablets had satisfactory physical properties and their swelling, in vitro mucoadhesion force and ex vivo mucoadhesion time were dependent on tablet composition. Highest swelling index and mucoadhesion time were detected for tablets containing 20% chitosan-10% alginate mixture. Most tablets exhibited burst release (~25%) during the first 2 h followed by sustained release for ~48 h. In vivo study showed that chitosan-alginate mucoadhesive tablets had ~2-fold higher P4 mean residence time in the blood and 5-fold higher bioavailability compared with oral P4. Further, same tablets showed 2-fold higher myometrium thickness in rabbit uterus compared with IM P4 injection. Conclusions: These results confirm the potential of these mucoadhesive vaginal tablets to enhance P4 efficacy and avoid the side effects associated with IM injection.

Objective: To develop mucoadhesive tablets for the vaginal delivery of progesterone (P4) to overcome its low oral bioavailability resulting from drug hydrophobicity and extensive hepatic metabolism. Methods: The tablets were prepared using mixtures of P4/Pluronic® F-127 solid dispersion and different mucoadhesive polymers. The tablets were evaluated for physical properties, swelling index, mucoadhesive properties and drug release kinetics. P4 pharmacokinetic and pharmacodynamic properties were evaluated in female rabbits and compared with vaginal micronized P4 tablets and intramuscular (IM) P4 injection, respectively. Results: The tablets had satisfactory physical properties and their swelling, in vitro mucoadhesion force and ex vivo mucoadhesion time were dependent on tablet composition. Highest swelling index and mucoadhesion time were detected for tablets containing 20% chitosan-10% alginate mixture. Most tablets exhibited burst release (~25%) during the first 2 h followed by sustained release for ~48 h. In vivo study showed that chitosan-alginate mucoadhesive tablets had ~2-fold higher P4 mean residence time in the blood and 5-fold higher bioavailability compared with oral P4. Further, same tablets showed 2-fold higher myometrium thickness in rabbit uterus compared with IM P4 injection. Conclusions: These results confirm the potential of these mucoadhesive vaginal tablets to enhance P4 efficacy and avoid the side effects associated with IM injection.