Raloxifene encapsulated spanlastic nanogel for the prevention of bone fracture risk via transdermal administration: Pharmacokinetic and efficacy study in animal model.

This research work is to evaluate spanlastic-loaded raloxifene (RLX) nanogel administration via the transdermal route to avoid its hepatic metabolism and to enhance the bioavailability for better management of osteoporosis. RLX-loaded spanlastic nanogel was prepared and characterized for its viscosity, pH, spreadability, and texture profile. The formulation was applied on the skin surface of the animal for pharmacokinetic evaluation, and later, the efficacy of the formulation was assessed in ovariectomized female Wistar rats. The nanogel was obtained with a viscosity (2552.66 ± 30.61 cP), pH (7.1 ± 0.1), and spreadability (7.1 ± 0.2 cm). The texture properties, cohesiveness, and adhesiveness of the nanogel showed its suitability for transdermal application. Nanogel showed no sign of edema and erythema in the skin irritation test which revealed its safety for transdermal application. The t1/2 obtained for RLX-spanlastic nanogel (37.02 ± 0.59 h) was much higher than that obtained for RLX-oral suspension (14.43 h). The relative bioavailability was found to be 215.96% for RLX-spanlastic nanogel, and the drug and formulation did not show any toxicity in any of the vital organs, as well as no hematological changes occurring in blood samples. In microarchitectural measurement, RLX-spanlastic nanogel exhibited no unambiguous deviations along with improved bone mineral density compared to the RLX suspension treated group. Transdermal administration of RLX-spanlastic nanogel showed significant improvement of drug bioavailability (approx. twice to oral administration) without any toxic effect in the treated rats. Hence, spanlastic nanogel could be a better approach to deliver RLX via transdermal route for the management of osteoporosis.

Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB).

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Precision engineering designed phospholipid-tagged pamidronate complex functionalized SNEDDS for the treatment of postmenopausal osteoporosis.

Disodium pamidronate, a second-generation bisphosphonate is a potent drug for the treatment of osteoporosis, which has been very well established by previous literature. It has very low oral permeability, leading to its low oral bioavailability, which restrict this drug to being administered orally. Therefore, the present research work includes the development of an orally effective nanoformulation of pamidronate. In this work, disodium pamidronate was complexed with phospholipon 90G for the enhancement of permeability and to investigate the phospholipon 90G-tagged pamidronate complex-loaded SNEDDS for oral delivery with promises of enhanced bioavailability and anti-osteoporotic activity. The rational design and optimization was employed using Central Composite Design (Design Expert® 12, software) to optimize nanoformulation parameters. In this work, a commercially potential self nano-emulsifying drug delivery system (SNEDDS) has been developed and evaluated for improved oral bioavailability and better clinical acceptance. The hot micro-emulsification and ultracentrifugation method with vortex mixing was utilized for effective tagging of phospholipon 90G with pamidronate and then loading into the SNEDDS nanocarrier. The optimized Pam-PLc SNEDDS formulation was characterized for particle size, PDI, and zeta potential and found to be 56.38 ± 1.37 nm, 0.218 ± 0.113, and 22.41 ± 1.14 respectively. Also, a 37.9% improved bioavailability of pamidronate compared to marketed tablet was observed. Similarly, in vivo pharmacokinetic studies suggest a 31.77% increased bone density and significant enhanced bone biomarkers compared to marketed tablets. The developed formulation is safe and effectively overcomes anti-osteoporosis promises with improved therapeutic potential. This work provides very significant achievements in postmenopausal osteoporosis treatment and may lead to possible use of nanotherapeutic-driven emerging biodegradable carriers-based drug delivery.

Magnetically recoverable Fe3O4 nanocatalyst for the synthesis of biodynamically significant 1H-pyrazolo[1,2-b]phthalazine-5,10-diones derivatives and its DFT study.

An environmentally sustainable and proficient method is reported for the synthesis of medicinally important pyrazolo[1,2-b] phthalazine dione derivatives by aqueous micellar medium catalysed by Fe3O4 NPs. Dialkyl acetylenedicarboxylate with isocyanides in the presence of phthalhydrazide is used as starting material. The main advantages of this protocol are the availability of starting materials, short reaction times, green solvents and practical simplicity.

Brain targeted delivery of carmustine using chitosan coated nanoparticles via nasal route for glioblastoma treatment.

This study aims to develop chitosan-coated PLGA nanoparticles intended for nose-to-brain delivery of carmustine. Formulations were prepared by the double emulsion solvent evaporation method and optimized by using Box-Behnken Design. The optimized nanoparticles were obtained to satisfactory levels in terms of particle size, PDI, entrapment efficiency, and drug loading. In vitro drug release and ex-vivo permeation showed sustained release and enhanced permeability (approx. 2 fold) of carmustine compared to drug suspension. The AUC0-t of brain obtained with carmustine-loaded nanoparticles via nasal administration in Albino Wistar rats was 2.8 and 14.7 times that of intranasal carmustine suspension and intravenous carmustine, respectively. The MTT assay on U87 MG cell line showed a significant decrease (P < 0.05) in the IC50 value of the formulation (71.23 µg ml-1) as compared to drug suspension (90.02 µg ml-1).These findings suggest chitosan coated nanoparticles could be used to deliver carmustine via intranasal administration to treat Glioblastoma multiforme.

Spanlastics a Novel Nanovesicular Carrier: Its Potential Application and Emerging Trends in Therapeutic Delivery.

Nanotechnology-based drug delivery system has played a very crucial role in overpowering the tasks allied with the conventional dosage form. Spanlastics, an elastic nanovesicle with an ability to carry wide range of drug molecules, make it a potential drug delivery carrier. Spanlastics have extended rising curiosity for diverse sort of route of administration. They can squeeze themselves through the skin pore due to elastic and deformable nature which makes them favorable for transdermal delivery. Spanlastics consist of non-ionic surfactant or blend of surfactants. Many researchers proved that spanlastics have been significantly augment therapeutic efficacy, enhanced drug bioavailability, and reduced drug toxicity. This review summarizes various vesicular systems, composition and structure of spanlastics, advantages of spanlastics over other drug delivery systems, and mechanism of drug penetration through skin. It also gives a brief on different types of drug encapsulated in spanlastics vesicles for the treatment of various diseases.

Efficient one-pot synthesis of substituted diphenyl 1, 3-thiazole through multicomponent reaction by using green and efficient Iron-catalyst via Cross-Dehydrogenative Coupling(CDC).

A clean and efficient, multi-component strategy for the synthesis of biologically important trisubstituted thiazole via the reaction of readily available barbituric acid, acetophenone, and aryl thioamides is reported in the presence of FeCl3.6H2O / O2(Air) in DMF solvent. The advantages of the present methodology include a one-pot reaction, environment-friendly approach, cost-effectiveness, broad substrate scope, operational simplicity, short reaction time, easy workup procedure, and high yields.

Repurposing pentosan polysulfate sodium as hyaluronic acid linked polyion complex nanoparticles for the management of osteoarthritis: A potential approach.

Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially weight-bearing joints like knee, hip, backbone, and phalanges. NSAIDs that are used for the management of inflammation associated with osteoarthritis have high side effects related to gastric upset, gastric ulcer, and long term treatment associated with liver and kidney damage. Nanotechnology has gained a huge scope for the management of arthritis as it can reach out to the deep inside the cell and alter cellular physiology as desired. The present study hypothesizes the use of polyion complex nanoparticles of hyaluronic acid linked Pentosan polysulfate sodium, a disease-modifying agent for the treatment of osteoarthritis administered through transdermal route. The hypothesis involves the use of drug repurposing as the drug was initially approved for interstitial cystitis, a condition of the urinary bladder associated with pain and swelling. Being very low oral bioavailability and gastric irritation profile, the transdermal route would be beneficial. To overcome the problem associated with the oral route, there is a need for the targeted approach that will particularly reach at inflammatory sites. Thereby transdermal delivery of hyaluronic acid linked Pentosan polysulfate sodium through polyion complex nanoparticle therapy will be a novel therapeutic approach to combat osteoarthritis.

Metal-free visible-light-mediated organophotoredox catalysis: synthesis of 3-functionalized indole via C-C, C-N bond formation.

A visible-light-mediated, mild and one-pot three-component reaction in the presence of organophotoredox catalyst Eosin Y using EtOH:H2O as reaction medium for the synthesis of 3-functionalized indole derivatives was developed. Visible light used in the protocol is green, inexpensive, readily available energy source. The sustainable reagents make the protocol compatible with green chemistry demands.