Andrographolide-loaded ethosomal gel for transdermal application: Formulation and in vitro penetration study

Background: Andrographolide is a phytoconstituent with anti-inflammatory activity, however, the compound’s poor oral bioavailability has hindered its effective formulation for oral administration. This study, therefore, aims to develop an ethosome for improving andrographolide penetration through the transdermal delivery system. Methods: This study developed 3 ethosome formulas with different andrographolide-phospholipid weight ratios (1:8, 1:9; 1:10), using the thin-layer dispersion-sonication method. Subsequently, the ethosomes were evaluated for particle size, polydispersity index, zeta potential, morphology, as well as entrapment efficiency, and incorporated into a gel dosage form. Subsequently, an in vitro penetration study was performed using Franz diffusion cells for 24 hours and the stability of the gels at 5 ± 2°C, 30 ± 2°C, and 40 ± 2°C, were studied for 3 months. Results: The results showed the optimal formula was E2, a 1:9 weight ratio formula of andrographolide and phospholipid. Based on the transmission electron micrograph, E2 possessed unilamellar, as well as spherical-shaped vesicles, and exhibited superior characteristics for transdermal delivery, with a particle size of 89.95 ± 0.75 nm, polydispersity index of 0.254 ± 0.020, a zeta potential of -39.3 ± 0.82 mV, and entrapment efficiency of 97.89 ± 0.02%. Furthermore, the cumulative andrographolide penetration and transdermal flux for the ethosomal gel of E2 (EG2) were 129.25 ± 4.66 µg/cm2 and 5.16 ± 0.10 µg/cm2/hours, respectively. All the ethosomal gel formulations exhibited improved penetration enhancement of andrographolide, compared to the nonethosomal formulations. Also, the andrographolide levels in the ethosomal and nonethosomal gels after 3 months ranged from 98.13 to 104.19%, 97.93 to 104.01%, and 97.23 to 102.26% at storage temperatures of 5 ± 2°C, 30 ± 2°C/RH 65% ± 5%, and 40 ± 2°C/RH 75% ± 5%, respectively. Conclusions: This study concluded that encapsulation into ethosome enhances andrographolide delivery through the skin.

Active Targeting Gold Nanoparticle for Chemotherapy Drug Delivery: A Review

Objective Active targeting strategy in chemotherapy drug delivery aims to improve the therapeutic outcomes and minimise the side effects of chemotherapeutics. This review discusses utilising ligands attached to gold nanoparticles (AuNPs) along with several specific ligands attached to AuNPs for active targeting in chemotherapy drug delivery. Key finding Antibodies, peptides, vitamins, DNA, polysaccharides, aptamers, and hormones showed active-targeting abilities as ligands attached to AuNPs. Active-targeting AuNPs enhanced cellular uptake and cytotoxicity in a specific cancer cell in vitro while reducing tumor growth in vivo by improving the photothermal, photodynamic and chemotherapy effects. Active-targeting ligands increased the internalization of AuNPs loaded onto the specific tumour site and minimised the accumulation in the normal site. Conclusion AuNPs with active-targeting ligands such as antibodies, peptides, vitamins, DNA polysaccharides, aptamers, and hormones can improve the therapeutic outcomes of chemotherapeutics and can attenuate the toxicity effect in normal cells. For further research and development, researchers should be addressing AuNP characterization, drug–ligand disposition, active-targeting AuNP quantification, and target-AuNPs pertinence concerning the desired therapeutic outcomes.

Synthesis of novel andostane-N-cyclohexyl-17-carboxamides, and their effect on the 5α-reductase isoform 2, the androgen receptor, and androgen-dependent glands

Background: Benign Prostatic Hyperplasia (BPH), and Prostate Cancer (PCa) are androgen-dependent diseases. PCa is associated with excessive signalling of the androgen receptor (AR) due to the binding of 5α-DHT and T. BPH is related to high levels of 5α-dihydrotestosterone (5α-DHT), biosynthesized from testosterone (T) by 5α-reductase (5RD5A). The inhibition of 5RD5A and the blockage of AR are targets for their treatment. In this study, the synthesis and determination of biological activity of the new N-cyclohexyl-3β-hydroxyandrosta-5,16-diene-17-carboxamide (6), N-cyclohexyl-3-oxoandrosta-4,6,16-triene-17-carboxamide (7), and N-cyclohexyl-3-oxoandrosta-4,16-diene-17-carboxamide (8) were carried out to find new drugs to improve these afflictions. Methods: The synthesis of 6 to 8 was confirmed by spectroscopic and spectrometric analyses. Competitive binding assays determined the affinity of 6 to 8 to the AR. The inhibitory activity of 5RD5A isoform 2 (5RD5A2) (IC50) was established by the conversion of [3H]-T to [3H]-5α-DHT and it was compared with finasteride (FIN). The pharmacological effect of 6 to 8 was determined on the weight of the prostate and seminal vesicles glands of castrated hamsters treated with T, and on the diameter size of their flank organs. Results: Compounds 7 and 8 bound lightly (ca. 15 %) to AR. Comparing to FIN (IC50 = 8.5 nM), 6 to 8 (IC50 = 0.169, 0.105 and 0.155 nM, respectively) showed higher potency as inhibitors of 5RD5A2. Compound 6 decreased the prostate and seminal vesicles weight, as well as the hamsters' diameter flank organs. However, 7 only decreased the diameter of flank organs. Surprisingly, 8 increased these pharmacological parameters. Conclusion: Androstane-17-caboxamide 6 is a 5RD5A2 inhibitor that reduces the weight of androgen-dependent glands such as the prostate, suggesting it could be a lead for new drugs to treat BPH and PCa.

The impacts of method selectivity and binders on the properties of carbamazepine granules and their applications: A case study

Background: Carbamazepine (CBZ) is a BCS II class drug, having many challenges in solubility, flowability, and compactibility. The study focused on the improvement of solubility, flow behavior, and drug release of carbamazepine. Methods: Low shear granulation (LSG), extrusion spheronization (ES), high shear granulation (HSG), fluid bed granulation (FBG), and hot melt granulation (HMG) methods were employed to prepare CBZ granules. Polyvinylpyrrolidone (PVP) K29/32, PVP K90, and Hydroxypropyl methylcellulose (HPMC) E5 were used as a binder. The drug to binder ratio was maintained in the proportion of 95:5. The nature of granules was analyzed by using X-ray Diffraction and Differential Scanning Calorimetry techniques. A powder flow tester was utilized to study the flow characteristics of the granules. Results: The HMG has successfully converted the crystalline structure of CBZ granules into an amorphous form. Dispersive and distributive mixing in the HMG has achieved better solid dispersion and fast drug release. The ES technique has reported the incompressible nature of the granules. PVP K90 and HPMC E5 were superior binders for imparting strength to the CBZ granules than PVP K29/32. The FBG has exhibited the free-flowing nature of granules due to their uniform and spherical shape. Conclusion: The HMG and FBG were the most effective methods that have remarkably improved drug release, flow properties, and compactibility of CBZ granules.

Antioxidant activity and nano delivery of the most frequently applied stilbene derivatives: A brief and recent review

As of recent, the appearance rate of several degenerative diseases and cancer influenced by oxidative stress continues to increase dramatically. Many compounds with high potential antioxidant activity have been explored and used extensively, i.e., as preventive or curative treatments. Stilbene and its derivates have high potential antioxidant activity contained in several botanical sources. To date, source exploration and antioxidant activity study of stilbene derivate has been reported. However, the nano-delivery of stilbene derivate meant to increase the antioxidant activity and stability is still a limited process. This review is devoted to brief and recent outlooks regarding the antioxidant activity and delivery system of the most frequently applied stilbene and its derivates, namely resveratrol and pterostilbene.

Colchicine for the Prevention of Myocardial Injury Following Elective PCI: A Randomized Clinical Trial

Purpose: Considering the potential benefits of colchicine in coronary artery diseases, we aimed to carry out the present study to assess the impact of colchicine in the prevention of myocardial injury following elective percutaneous coronary intervention (PCI). Methods: A randomized, single-blinded, clinical trial was carried out on 102 patients undergoing elective PCI. All patients received the standard treatment prior to performing PCI. Moreover, the intervention group received 1, 0.5, 0.5 mg colchicine 12 to 18 hours before, 30-60 min before, and 12 hours after PCI, respectively. Serum concentrations of cardiac troponin I (cTnI) were measured before, 8, and 24 hours after the procedure to assess myocardial damage during PCI. Results: There were no significant differences in cTnI levels at baseline (P = 0.839), 8 (P = 0.729), and 24 hours (P = 0.398) after PCI between the intervention and the control groups. Likewise, no significant differences were seen regarding the mean differences of cTnI at baseline and 8 hours (P =0.190), at baseline and 24 hours (P = 0.780), and 8 and 24 hours after PCI (P = 0.680) in both groups. Conclusion: The study did not support the potential benefit of colchicine in the prevention of myocardial injury following elective PCI. Conducting well-designed randomized clinical trials with adequate sample size is recommended.

Potential anthelmintic and antioxidant activities of Jasminum fruticans L. and its phytochemical analysis

Background: Ethnobotanical investigations conducted in Turkey demonstrated that Jasminum fruticans L. extract and fruit juice had been used against parasites in animals. In this study, the possible antihelmintic activity of various J. fruticans extracts contributing to its traditional use, was relatively assessed. In addition, the antioxidant potentials and phytochemical composition of the extracts were investigated since there is a relationship between helminthiasis, oxidative stress and phenolic metabolites. Methods: In this study, aerial parts of J. fruticans were subsequently extracted using n-hexane, ethyl acetate (EtOAc) and methanol (MeOH). In vivo anthelmintic activitiy of the extracts was compared with albendazole used as a reference in adult earthworms. Various methods, including free radical scavenging and metal-related activity assays, were used to assess the antioxidant capacity of the above-mentioned extracts. Assessment of phenolic composition was accomplished through total phenolic, phenolic acid, and flavonoid content assays as well as liquid chromatography-mass spectrometry (LC-MS/MS) using multiple reaction monitoring (MRM) scan modes. Further chlorogenic acid (3-O-caffeoylquinic acid) contents of extracts were quantified using high-performance thin-layer chromatography (HPTLC). Results: Between all tested extracts, MeOH extract at a quantity of 50.0 mg/mL, paralysed worms in 8.1 min and killed them in 12.8 min, showing a high anthelmintic effect similar to albendazole. Similarly, in vitro DPPH radical scavenging activity, cupric ion reduction and total antioxidant capacity experiments demonstrated that MeOH extract had significant antioxidant activity. Further phytochemical screening showed that MeOH extract was richer regarding phenolic metabolites. Chlorogenic acid, ferulic acid, caffeic acid and gallic acid were only detected in the MeOH extract. Conclusion: Results justify and support the use of J. fruticans in traditional medicine as an anthelmintic agent. Furthermore, a positive correlation was found between the strong antioxidant capacity along with the phenolic composition determined in the MeOH extract and anthelmintic activity.

Pharmaceutical properties of sour tea (Hibiscus sabdariffa), Toward an ideal treatment for Hypertension

High blood pressure is the main risk factor for cardiovascular disease and should be controlled primarily by changes in lifestyle, such as regular exercise, a low-salt diet, and weight loss in overweight or obesity. If lifestyle changes are not enough, many types of medications can be used to control high blood pressure; however, side effects constitute one of the most critical limitations of conventional medicines associated with high blood pressure. For this reason, the use of traditional and herbal medicines has been welcomed by the public for many years. Sour tea (Hibiscus sabdariffa) is one of the most suitable herbal medicines for hypertension. According to research results, sour tea has the same effect as conventional medicines without serious side effects. The present study introduces sour tea as a suitable herbal medicine for high blood pressure to provide readers of this article with a comprehensive understanding of the medicinal properties of sour tea for the treatment of hypertension and its effects on several other common diseases, including cancer.

A Terbium Metal–Organic Framework Platform for Determination of Lamotrigine in Exhaled Breath Condensate

Background: Lamotrigine is widely used in the management of partial epilepsy, generalized tonic-clonic epilepsy and Lenox-Gastut syndrome and an add-on therapy in the treatment of complex and simple partial seizures and secondarily generalized tonic-clonic seizures resistant to multiple drug therapy. Methods: In the current study, a fluorometric nanoprobe based on metal–organic frameworks (MOF) was designed for the determination of lamotrigine in exhaled breath condensate (EBC). The MOF nanoprobe consisted of Tb3+ ions as metal part and dimethylformamide (DMF) and 1,10-phenanthroline (Phen) as organic parts of nanoprobe. Results: The used probe shows a week fluorescence in alkaline media owing to an energy transfer from nitrogen groups of DMF and Phen on carbonyl group of DMF as an antenna for Tb3+ luminescence. However, its fluorescence is enhanced in acidic conditions by protonation of DMF nitrogen atoms and Phen and deactivation of energy transfer pathways of nitrogen groups to carbonyl group. Lamotrigine addition to this fluorescent system leads to quenching in the fluorescence intensity due to reactivation of the above mentioned energy transfer pathways resulting in competitive interaction with H+ ions. Moreover, the inner filter effect (IFE) of lamotrigine on DMF–Tb–Phen MOF NPs is considered as another reason for the observed quenching in the fluorescence of DMF–Tb–Phen MOF NPs. The intensity of the fluorescence was recorded at λem = 545 nm and the difference between fluorescence signal in the absence and presence of lamotrigine was the analytical response. The factors affected on experimental conditions were optimized utilizing a multivariate optimization technique. The validation of nanoprobe response to lamotrigine gives a linear relationship in the range of 0.05 to 2.0 µg⋅mL‒1 with a detection limit of 11.0 ng⋅mL‒1 for lamotrigine. Conclusion: The developed method reveals good repeatability and selectivity for lamotrigine in real samples.