Assay and drug development technologies最新文献

Low water solubility is the main hindrance in the growth of pharmaceutical industry. Approximately 90% of newer molecules under investigation for drugs and 40% of novel drugs have been reported to have low water solubility. The key and thought-provoking task for the formulation scientists is the development of novel techniques to overcome the solubility-related issues of these drugs. The main intention of present review is to depict the conventional and novel strategies to overcome the solubility-related problems of Biopharmaceutical Classification System Class-II drugs. More than 100 articles published in the last 5 years were reviewed to have a look at the strategies used for solubility enhancement. pH modification, salt forms, amorphous forms, surfactant solubilization, cosolvency, solid dispersions, inclusion complexation, polymeric micelles, crystals, size reduction, nanonization, proliposomes, liposomes, solid lipid nanoparticles, microemulsions, and self-emulsifying drug delivery systems are the various techniques to yield better bioavailability of poorly soluble drugs. The selection of solubility enhancement technique is based on the dosage form and physiochemical characteristics of drug molecules.

Liposomes are unique novel drug delivery carriers that favor the effective transportation of pharmaceuticals. These vesicles acquire one or more phospholipid bilayer membranes, and an inner aqueous core can carry both aqueous and lipid drugs. While hydrophilic molecules can be confined in the aqueous core, hydrophobic molecules are injected into the bilayer membrane. Liposomes have many benefits as a drug delivery method, including biocompatibility, the capacity to carry large drug payloads, and a variety of physicochemical and biological parameters that can be altered to influence their biological characteristics. In addition, being a size of 10-100 nm range can have numerous additional benefits, including enhanced pharmacokinetics, clever escape from the reticuloendothelial system, greater in vivo stability, longer and site-specific administration, and increased internalization in tumor tissue (enhanced permeability and retention impact). The current review focuses on the structural composition of liposomes, formulation technologies, and suitable case studies for optimizing biopharmaceutical performance. Moreover, clinical trials and marketed formulations of liposomes have been also stated in the prior art.

Poorly soluble drug molecules/phytoconstituents are still a growing concern for biopharmaceutical delivery in the body. Polymeric micelles are the amphiphilic block copolymers and have been widely investigated as targeted nanocarriers for the treatment of various ailments. The versatility of nanocarriers is the self-assembling properties in the aqueous medium and forms a stable isotropic system in vivo. The hydrophobic core-hydrophilic shell configuration of the polymers used to the mixed micelles makes easy encapsulation of hydrophobic and hydrophilic drugs into the core. Polymeric micelles can also be combined with targeting ligands that increase their uptake by specific cells, decreasing off-target effects, and provide enhanced therapeutic effect. In the present review, we primarily focused on a critical appraisal of Polymeric micelles along with the method of preparation, mechanism of micelle formulation, and the ongoing formulations under clinical trials. In addition, the biological applications of this isotropic nanocarrier have been duly presented in each route of administration along with suitable case studies.

Drug absorption is improved by the intranasal route's wide surface area and avoidance of first-pass metabolism. For the treatment of central nervous system diseases such as migraine, intranasal administration delivers the medication to the brain. The study's purpose was to develop an in situ nasal hydrogel that contained liposomes that were loaded with sumatriptan succinate (SS). A thin-film hydration approach was used to create liposomes, and a 3² factorial design was used to optimize them. The optimized liposomes had a spherical shape, a 171.31 nm particle size, a high drug encapsulation efficiency of 83.54%, and an 8-h drug release of 86.11%. To achieve in situ gel formation, SS-loaded liposomes were added to the liquid gelling system of poloxamer-407, poloxamer-188, and sodium alginate. The final product was tested for mucoadhesive strength, viscosity, drug content, gelation temperature, and gelation time. Following intranasal delivery, in vivo pharmacokinetic investigations showed a significant therapeutic concentration of the medication in the brain with a C_max value of 167 ± 78 ng/mL and an area under the curve value of 502 ± 63 ng/min·mL. For SS-loaded liposomal thermosensitive nasal hydrogel, significantly higher values of the nose-to-brain targeting parameters, that is, drug targeting index (2.61) and nose-to-brain drug direct transport (57.01%), confirmed drug targeting to the brain through the nasal route. Liposomes containing thermosensitive in situ hydrogel demonstrated potential for intranasal administration of SS.

The severity and prevalence of cancer in modern time are a huge global health burden. Continuous efforts are being made toward the development of newer therapeutic candidates to treat and manage this ailment. The dihydropyrimidinone scaffold is one of the key nuclei that have been highly explored and investigated against cancer. It has the potential to combat the consequences of cancer by interacting with several biological targets. Tubulin polymerization inhibition is one such strategy to prevent the progression of cancer. In the presented work, we have synthesized a series of sixteen dihydropyrimidinone derivatives by following a rational drug design. The synthesized compounds have been characterized by ¹H NMR and ¹³C NMR and were further evaluated for cytotoxic activity against breast cancer cell lines (MCF-7 and MDA-MB-231), lung cancer cell lines (A549), and colon cancer cell lines (HCT-116). Compounds 5D and 5P were found most potent and revealed a better cytotoxic activity compared with the standard drug colchicine. Furthermore, the tubulin polymerization inhibition assay revealed that compound 5D showed better inhibition than colchicines, whereas compound 5P revealed an almost equal inhibition to that of colchicine. Furthermore, to investigate the possible mode of action and binding patterns, compounds 5P and 5D were subjected to molecular docking against tubulin (Protein Data Bank ID: ISA0). The results showed that compounds revealed significant interactions and were well occupied inside the cavity of tubulin. The compounds 5D and 5P may serve as new leads in drug development against cancer.

Cisplatin is the most often used chemotherapy in the treatment of ovarian cancer (OC), however long-term usage leads to drug resistance and treatment failure. Silibinin is a sparingly water-soluble natural compound with well-known anticancer effects. The use of lipid-based delivery systems is a potential approach for enhancing silibinin's water solubility. In this study, nanostructured lipid carriers (NLCs) containing silibinin were prepared and their inhibitory effects were tested in combination with cisplatin against sensitive/resistant A2780 OC cells. Silibinin-loaded NLCs (silibinin-NLCs) were prepared by the hot homogenization method, and their size, shape, zeta potential (ZP), and encapsulation efficiency (EE), as well as their inhibitory effects, were examined in combination with cisplatin against sensitive/resistant A2780 OC cells. Formulation of silibinin-NLCs using cocoa butter led to spherical-shaped NLCs with a size of 95 nm and EE of 98%. The ZP and the dispersion index of the silibinin-NLCs were -27.12 ± 0.13 mv and 0.12 ± 0.04, respectively. The release kinetics of silibinin-NLCs was best fitted with the zero-order model. The combination of cisplatin and silibinin-NLCs sensitized the cisplatin-resistant A2780 OC cells and exhibited a more synergistic inhibitory effect on A2780 cells as compared with the combination of cisplatin and plain silibinin. The optimized silibinin-NLCs can be considered a suitable drug delivery system for the inhibition of cisplatin-resistant OC cells.

Simvastatin (SIM) is known to lower cholesterol levels and is speculated in the pathogenesis of Alzheimer's disease. In this study, the bioanalytical method of SIM SNEDDS was developed and validated for the estimation of SIM in the rat's plasma using reverse-phase high-performance liquid chromatography. C-18 reverse-phase octadecylsilyl column was used to validate the method. Atorvastatin (ATV) was used as an internal standard. Gradient elution was performed using acetonitrile and water in a ratio of 90:10 with a flow rate of 1 mL/min. The chromatogram of these both compounds SIM and ATV was detected at a wavelength of 238 and 244 nm. The drugs were extracted from the plasma samples using the protein precipitation method. The retention time of SIM and ATV was found to be 3.720 and 8.331 min, respectively. The developed method was found to be linear in the range between 50 and 250 ng/mL, with a regression coefficient (r²) of 0.9994. According to ICH M10 guidelines, the method was validated. The percent of drug recovery was more than 95% and the % relative standard deviation was <2% in the replicate studies, which showed that the method was accurate and precise. The limit of detection and limit of quantification were found in rat plasma to be 0.12 and 0.38 ng/mL, respectively. The obtained result indicated that the developed method was successful in estimating SIM in rat plasma and passed all validation test parameters.