اريج وهاب عبد الجليل الحاج عيسى

Bortezomib (BTZ) is a selective proteasome inhibitor whose anticancer activity results from disrupting regulated protein turnover, leading to apoptosis. It is highly potent but lacks specificity and shows limited activity against solid tumors. This project aims to formulate BTZ as Human Serum Albumin Nanoparticles (HSA NPs) to improve its sensitivity and selectivity towards solid tumors. These albumin nanoparticles enable both passive and active targeting. Passive targeting occurs through the enhanced permeation and retention (EPR) effect of nanoparticles, while the overexpression of albumin receptors on tumor cells facilitates active targeting. BTZ HSA NPs have been prepared using the desolvation method. In vitro characterisation involved particle size (PS), polydispersity index (PDI), entrapment efficiency (EE%), particle morphology, and an in vitro release study. The optimised formula was then evaluated for its anti-tumor activity in vivo using BALB/c mice, where the tumor volume was measured, and a histopathological analysis of the tumor tissue was performed. The optimised formula has PS, PDI, and EE% of (28) nm, 0.045, and 36%, respectively. The particles exhibit an almost spherical morphology and a controlled-release profile, with approximately 85% of BTZ released within 24 hours. On the other hand, in vivo, the NPs showed a significant decrease in tumor volume compared with the group that received only pure BTZ or phosphate-buffered saline (PBS). The histopathological study showed better tumor aggressiveness (lower mitotic count and nuclear pleomorphism), increased apoptosis, and improved immune cell infiltration. Formulation of BTZ as HSA NPs is a successful approach to enhance its activity and selectivity against cancer cells. The desolvation method is a reliable, reproducible method for obtaining these NPs.

Introduction Bortezomib (BTZ) is a proteasome inhibitor approved for the treatment of multiple myeloma. It is under investigation for use in the treatment of other solid tumors, such as breast and prostate cancers. BTZ is known for its high potency, limited aqueous solubility, and systemic toxicity. These characteristics restrict its clinical application. This study aims to formulate BTZ in the form of bovine serum albumin (BSA) nanoparticles (NPs) to enhance its anticancer targeting. The Box–Behnken experimental design was employed to optimize the formulation of BTZ-loaded BSA NPs. Methods BTZ BSA NPs were prepared through the desolvation method by using glutaraldehyde (Glut) as a crosslinker. The Box–Behnken design was employed as an experimental design tool to investigate the impact of formulation parameters, specifically the amount of BTZ, BSA, and antisolvent volume, on outcomes, including particle size (PS), entrapment efficiency (EE%), and polydispersity index (PDI). The morphology of the prepared NPs was examined using a transmission electron microscope (TEM), while a compatibility study was conducted using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results The optimized formulation resulted in a mean PS, EE%, and PDI of 74 nm, 68%, and 0.007, respectively. The BTZ BSA NPs exhibited a sustained in vitro release profile over 24 hours. TEM revealed that the prepared NPs had an almost spherical morphology. FTIR and DSC revealed that BTZ was encapsulated well within the prepared NPs with minimal decomposition and/or degradation. Discussion The optimized BTZ BSA NPs exhibited uniform nanosize, high entrapment efficiency, and sustained drug release, confirming the effectiveness of Box–Behnken optimization. Encapsulation within the cross-linked albumin matrix protected BTZ from hydrolytic degradation, enhanced its stability, and provided controlled release, supporting its potential for improved anticancer activity and reduced systemic toxicity. Conclusion The use of experimental design is a valuable tool for optimizing the formulation of BTZ BSA NPs, achieving the required PS, high EE%, and low PDI

Background: Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) having poor water solubility and high permeability. The study aimed to prepare, characterize, and evaluate ibuprofen nanosuspensions to enhance its solubility and dissolution rate. Materials & Methods: This was an experimental and laboratory-based study. Nanosuspensions of ibuprofen were formulated using three different polymers-PVP K30, Poloxamer 188, and HPMC E50-at various drug-to-polymer ratios (1:1, 1:2, 1:3). The study was conducted in a controlled laboratory environment, typically in a pharmaceutical or chemical research laboratory equipped with instruments like particle size analyzers, scanning electron microscopes, and dissolution apparatus. The formulation and characterization experiments were performed in compliance with standard protocols for nanoparticle formulation and pharmaceutical analysis Results: All ibuprofen nanosuspensions were within the nano size range (123-564.5 nm), with the smallest particle size (123 nm) observed for PVP K30 at a 1:1 ratio. The PDI ranged from 0.008 to 0.071, and the specific surface area (SSA) ranged from 18.6 to 3.39 m²/g. Saturated solubility of ibuprofen increased by approximately six-fold compared to the pure drug. Entrapment efficiency ranged from 85% to 97%, while the dissolution rate showed a significant improvement, with 98% of the drug released within 15 minutes, compared to 25% release from pure ibuprofen in the same period. Conclusion: The solvent- Anti-solvent technique is effective for producing ibuprofen Nano-suspensions, significantly enhancing the solubility and dissolution rate of the drug. This formulation approach holds promise for improving the bioavailability of poorly water-soluble drugs like ibuprofen.

Nimodipine (NMD) is a dihydropyridine calcium channel blocker useful for the prevention and treatment of delayed ischemic effects. It belongs to class ? drugs, which is characterized by low solubility and high permeability. This research aimed to prepare Nimodipine nanoparticles (NMD NPs) for the enhancement of solubility and dissolution rate. The formulation of nanoparticles was done by the solvent anti-solvent technique using either magnetic stirrer or bath sonicator for maintaining the motion of the antisolvent phase. Five different stabilizers were used to prepare NMD NPs( TPGS, Soluplus®, HPMC E5, PVP K90, and poloxamer 407). The selected formula F2, in which Soluplus has been utilized as a stabilizer, has a particle size (77 nm) and polydispersity index (PDI) (0.016). The formulas with the smallest particle size were freeze dried with the addition of 1 % w/w mannitol as cryoprotectant. The saturation solubility of NMD in the prepared nanoparticles was increased twenty four-folds, and the complete dissolution was achieved at 90 minutes compared with pure NMD, which reaches only 6%. The formation of hydrogen bonding between NMD and the polymer or the cryoprotectant, as confirmed by the FTIR study. In conclusion, the preparation of NMD as polymeric nanoparticles is a useful technique for enhancing the solubility and dissolution rate.

Nimodipine (NMD) is a Dihydropyridine calcium channel blocker with some selectivity to the cerebral vasculature administered to minimize the neural deficit for patients with subarachnoid hemorrhage. The NMD is characterized by low bioavailability because of its low water solubility and extensive first-pass metabolism. This research aims to improve bioavailability by enhancing the solubility via the formulation of nanoparticles (NPs) and decreasing the first-pass metabolism by incorporation the prepared NMD NPs in orodispersible tablets (ODTs). The preparation of NMDNPs was done by solvent antisolvent precipitation technique using three different stabilizers (TPGS, Soluplus®, and PXM 407) in two drugs: stabilizer ratios (1: 2 and 1: 3) and two different injection speed (30 and 60 mL/hr) of the solvent to the antisolvent phase. The optimized formula is composed of 30 mg NMD, 60 mg Soluplus® and 1% w/w mannitol as cryoprotectant. The degree of crystallinity of pure NMD and NMD NPs was examined by X-ray diffraction. It was established that the degree of crystallinity had been reduced, which is an indication of converting the crystalline NMD into a more amorphous form. ODTs incorporating NMD NPs show a complete dissolution after forty minutes in SSF with 0.5% Brij-35 compared with ODT incorporating pure NMD, which reaches only 50% in the same duration. It is concluded that formulation NMD as NPs to be incorporated in ODT is an excellent technique to enhance the dissolution rate and promoting pre-gastric absorption.

Selexipag is first in class orally active, selective nonprostanoid prostacyclin receptor agonist with a long halflife. It has low oral bioavailability due to a poor dissolution rate, which is considered a rate-limiting step for drug absorption. Nanocrystals (NCs) formulation is an attractive approach for enhancing the poorly soluble drug's saturation solubility and dissolution rate. They offer the advantages of crystalline state, high drug loading capacity, and simple preparation method. This study aims to prepare and characterize Selexipag NCs, filled in hard gelatin capsule in attempt to improve its solubility and dissolution rate. The effect of stabilizer type and preparation methods on the NC particle size and polydispersity index were evaluated to select the most stable formula. The results revealed that the formula (F7) prepared by the solvent antisolvent precipitation with the ultrasonication method (which contain SLX: Soluplus® at a ratio of 1: 2) has the smallest mean particle size (38.5 nm) and appropriate polydispersity index (0.12); hence it was selected as the optimal formula. Simultaneously, the data from powder X-ray diffraction shows no reduction in the crystallinity of drugs. SLX NCs exhibit increased saturation solubility by several folds than pure SLX. The hard gelatin capsule containing the lyophilized powder showed a faster dissolution profile (complete drug release in 15 min) relative to pure SLX (0.1% during the same time).