Preparation and Characterization of Novel Polyelectrolyte Liposomes Using Chitosan Succinate Layered over Chitosomes: A Potential Strategy for Colon Cancer Treatment.

Chitosan succinate is distinguished by its ability to shield the loaded drug from the acidic environment, localize and keep the drug at the colon site, and release the drug over an extended time at basic pH. The current study attempts to develop polyelectrolyte liposomes (PEL), using chitosan and chitosan succinate (CSSC), as a carrier for liposomal-assisted colon target delivery of 5 fluorouracil (5FU). The central composite design was used to obtain an optimized formulation of 5FU-chitosomes. The chitosan-coated liposomes (chitosomes) were prepared by thin lipid film hydration technique. After that, the optimized formulation was coated with CSSC, which has several carboxylic (COOH) groups that produce an anionic charge that interacts with the cation NH2 in chitosan. The prepared 5FU-chitosomes formulations were evaluated for entrapment efficiency % (EE%), particle size, and in vitro drug release. The optimized 5FU-chitosomes formulation was examined for particle size, zeta potential, in vitro release, and mucoadhesive properties in comparison with the equivalent 5FU-liposomes and 5FU-PEL. The prepared 5FU-chitosomes exhibited high EE%, small particle size, low polydispersity index, and prolonged drug release. PEL significantly limited the drug release at acidic pH due to the deprotonation of carboxylate ions in CSSC, which resulted in strong repulsive forces, significant swelling, and prolonged drug release. According to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, PEL treatment significantly decreased the viability of HT-29 cells. When compared to 5FU-liposome and 5FU-chitosome, the in vivo pharmacokinetics characteristics of 5FU-PEL significantly (p < 0.05) improved. The findings show that PEL enhances 5FU permeability, which permits high drug concentrations to enter cells and inhibits the growth of colon cancer cells. Based on the current research, PEL may be used as a liposomal-assisted colon-specific delivery.

Nanostructured Lipid Carriers (NLCs) as Effective Drug Delivery Systems: Methods of Preparation and their Therapeutic Applications.

One of the drug delivery technologies is nanostructured lipid carriers (NLCs), which improve drug permeability and thus bioavailability. NLCs are nanoparticles made from a lipid matrix made up of a mixture of solid and liquid lipids. The inclusion of liquid lipids is useful in lowering the ordered structure of solid lipids, increasing nanoparticle loading capacity, and drug entrapment efficiency within NLCs. Hot homogenization, cold homogenization, micro-emulsion, emulsification-solvent diffusion, high shear homogenization, and/or ultrasonication techniques, double emulsion technique, melting dispersion method, membrane contractor technique, and evaporation solvent injection are some of the methods that can be used to make NLCs. Both hydrophilic and lipophilic medicines can be carried out by NLCs. They can deliver medications in a variety of ways, including oral, topical, transdermal, parenteral, and ophthalmic. During the process of preparing this review article, several distinct studies and patent reports about various methods of NLCs formulations, their various therapeutic applications, and various routes of administration were investigated and discussed. The study conducts an in-depth evaluation of the most recent research publications and patents. NLCs have been utilized to treat a variety of disorders, including cancer, fungal infections, bacterial infections, inflammation, liver diseases, and ocular infections, due to their benefits. They can deliver medications to specific locations throughout the body, allowing for drug targeting and a reduction in unwanted side effects. They can also be used to improve bioavailability, reduce the medication's supplied dose, and improve the drug's pharmacological activity.

Marula oil nanoemulsion improves motor function in experimental parkinsonism via mitigation of inflammation and oxidative stress.

Introduction: Parkinson's disease (PD) is a neurologic condition exhibiting motor dysfunction that affects old people. Marula oil (M-Oil) has been used longley in cosmetics and curing skin disorders. M-Oil is particularly stable due to its high concentration of monounsaturated fatty acids and natural antioxidants. The current study formulated M-Oil in an o/w nanoemulsion (M-NE) preparations and tested its anti-inflammatory and antioxidant actions against experimental parkinsonism. Methods: Four experimental groups of male albino mice were used and assigned as vehicle, PD, PD + M-Oil and PD + M-NE. Locomotor function was evaluated using the open field test and the cylinder test. Striatal samples were used to measure inflammatory and oxidative stress markers. Results: The results indicated poor motor performance of the mice in PD control group then, improvements were recorded after treatment with crude M-Oil or M-NE. In addition, we found high expression and protein of inflammatory markers and malondialdehyde levels in PD group which were downregulated by using doses of crude M-Oil or M-NE. Hence, formulating M-Oil in form of M-NE enhanced its physical characters. Discussion: This finding was supported by enhanced biological activity of M-NE as anti-inflammatory and antioxidant agent that resulted in downregulation of the inflammatory burden and alleviation of locomotor dysfunction in experimental PD in mice.

Ginger Oil Nanoemulsion Formulation Augments Its Antiproliferative Effect in Ehrlich Solid Tumor Model.

Cancer is a disease that is characterized by uncontrolled cell proliferation. Breast cancer is the most prevalent cancer among women. Ginger oil is a natural cancer fighter and anti-oxidant. However, the minimal absorption of ginger oil from the gastrointestinal tract accounts for its limited medicinal efficacy. The present study was designed to evaluate the efficacy of a nanoemulsion preparation of ginger oil on its oral bioavailability and in vivo anti-cancer efficacy. Ginger oil nanoemulsion was prepared by a high-pressure homogenization technique using different surfactants (Tween 20, 40, and 80). The prepared formulations were evaluated for droplet size, polydispersity index (PDI), zeta potential (ZP), pH, viscosity, and stability by calculating the creaming index percentage. The best formulation was evaluated for shape by TEM. The antitumor activity of the best nano-formulation was determined in comparison with the free oil using the in vivo Ehrlich solid tumor (EST) model. The prepared ginger oil nanoemulsion formulations exhibited acceptable droplet size in the range from 56.67 ± 3.10 nm to 357.17 ± 3.62 nm. A PDI of less than 0.5 indicates the homogeneity of size distribution. The oil globules possessed a negative charge ranging from -12.33 ± 1.01 to -39.33 ± 0.96 mV. The pH and viscosity were in the acceptable range. The TEM image of the best formulation appeared to be spherical with a small size. The ginger oil nanoemulsion reduced in vivo tumor volume and weight, extended animals' life span, and ameliorated liver and kidney function in EST-bearing mice. These effects were superior to using free ginger oil. Collectively, the present study demonstrated that the ginger oil nanoemulsion improved oral absorption with a subsequent enhancement of its anti-proliferative efficacy in vivo, suggesting a nano-formulation of ginger oil for better therapeutic outcomes in breast cancer patients.

Enhanced Skin Permeation and Controlled Release of ß-Sitosterol Using Cubosomes Encrusted with Dissolving Microneedles for the Management of Alopecia.

The use of synthetic medication for treating alopecia is restricted because of systemic exposure and related negative effects. Beta-sitosterol (ß-ST), a natural chemical, has lately been studied for its potential to promote hair development. The cubosomes with dissolving microneedles (CUBs-MND) created in this study may be a useful starting point for the creation of a sophisticated dermal delivery system for ß-ST. Cubosomes (CUBs) were prepared by the emulsification method, using glyceryl monooleate (GMO) as a lipid polymer. CUBs were loaded with dissolving microneedles (MND) fabricated with HA and a PVP-K90 matrix. An ex vivo skin permeation study and an in vivo hair growth efficacy test of ß-ST were performed with both CUB and CUB-MND. The average particle size of the CUBs was determined to be 173.67 ± 0.52 nm, with a low polydispersity index (0.3) and a high zeta potential value that prevents the aggregate formation of dispersed particles. When compared to CUBs alone, CUBs-MND displayed higher permeating levels of ß-ST at all-time points. In the animals from the CUB-MND group, significant hair development was observed. According to the results of the current investigation, CUBs that integrate dissolving microneedles of ß-ST are superior in terms of transdermal skin penetration and activity for the treatment of alopecia.

Optimization and In Vitro Characterization of Telmisartan Loaded Sodium Alginate Beads and Its In Vivo Efficacy Investigation in Hypertensive Induced Animal Model.

BACKGROUND: Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. METHODS: For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. RESULTS: The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. CONCLUSIONS: It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation's extended anti-hypertensive activity in animal models.

Preparation and Optimization of Itraconazole Transferosomes-Loaded HPMC Hydrogel for Enhancing Its Antifungal Activity: 23 Full Factorial Design.

Itraconazole (ITZ) is a triazole antifungal agent characterized by broad-spectrum activity against fungal infections. The main drawback of ITZ, when applied topically, is the low skin permeability due to the stratum corneum, the outermost layer of the skin, which represents the main barrier for drug penetration. Therefore, this study aimed to prepare itraconazole as transferosomes (ITZ-TFS) to overcome the barrier function of the skin. ITZ-TFSs were prepared by thin lipid film hydration technique using different surfactants, sodium lauryl sulfate (SLS) and sodium deoxycholate (SDC). The prepared ITZ-TFS were evaluated for entrapment efficiency (EE) %, particle size, polydispersity index (PDI), zeta potential, and in vitro drug release to obtain an optimized formula. The surface morphology of the optimized formula of ITZ-TFS was determined by transmission electron microscope (TEM). The optimized formulation was prepared in the form of gel using hydroxyl propyl methyl cellulose (HPMC) gel base. The prepared ITZ-TFS gel was evaluated for homogeneity, drug content, spreadability, pH, and in vitro antifungal activity in comparison with the free ITZ gel. The prepared ITZ-TFS formulations exhibited high EE% ranging from 89.02 ± 1.65% to 98.17 ± 1.28% with particle size ranging from 132.6 ± 2.15 nm to 384.1 ± 3.46. The PDI for all ITZ-TFSs was less than 0.5 and had a negative zeta potential. The TEM image for the optimized formulation (ITZ-TFS4) showed spherical vesicles with a smooth surface. The prepared gels had good spreadability, pH, and acceptable drug content. ITZ-TFS gel showed higher antifungal activity than free ITZ gel as determined by zone of inhibition. ITZ was successfully prepared in form of TFSs with higher antifungal activity than the free drug.

The Combined Anti-Tumor Efficacy of Bioactive Hydroxyapatite Nanoparticles Loaded with Altretamine.

In the current study, the combined anti-tumor efficacy of bioactive hydroxyapatite nano- particles (HA-NPs) loaded with altretamine (ALT) was evaluated. The well-known fact that HA has great biological compatibility was confirmed through the findings of the hemolytic experiments and a maximum IC50 value seen in the MTT testing. The preparation of HA-NPs was performed using the chemical precipitation process. An in vitro release investigation was conducted, and the results demonstrated the sustained drug release of the altretamine-loaded hydroxyapatite nanoparticles (ALT-HA-NPs). Studies using the JURKAT E6.1 cell lines MTT assay, and cell uptake, as well as in vivo pharmacokinetic tests using Wistar rats demonstrated that the ALT-HA-NPs were easily absorbed by the cells. A putative synergism between the action of the Ca2+ ions and the anticancer drug obtained from the carrier was indicated by the fact that the ALT-HA-NPs displayed cytotoxicity comparable to the free ALT at 1/10th of the ALT concentration. It has been suggested that a rise in intracellular Ca2+ ions causes cells to undergo apoptosis. Ehrlich's ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half.

Review on Different Vesicular Drug Delivery Systems (VDDSs) and Their Applications.

BACKGROUND: Colloidal dispersions, also known as vesicular drug delivery systems (VDDSs), are highly ordered assemblies composed of one or more concentric bilayers formed by the self-assembly of amphiphilic building blocks in the presence of water. OBJECTIVE: VDDSs are important to target the entrapped drugs at specific sites inside the body, control the drug release, enhance the drug bioavailability, and reduce undesired side effects. METHODS: There are different types of VDDSs suitable for the entrapment of both hydrophilic and lipophilic drugs. According to the patent composition, VDDSs are classified into lipid-based and nonlipid- based VDDSs. RESULTS: There are different types of VDDSs which include liposomes, ethosomes, transferosomes, ufasomes, colloidosomes, cubosomes, niosomes, bilosomes, aquasomes, etc. Conclusion: This review article aims to address the different types of VDDSs, their advantages and disadvantages, and their therapeutic applications.

Microneedle mediated transdermal delivery of ß-sitosterol loaded nanostructured lipid nanoparticles for androgenic alopecia.

Plant-derived 5 α-reductase inhibitors, such as ß-sitosterol and phytosterol glycosides, have been used to treat androgenic alopecia, but their oral absolute bioavailability is poor. This study aimed to develop a transdermal drug delivery system of ß-sitosterol (BS) using a nanostructured lipid carrier (NLC) incorporated into polymeric microneedles (MN). Using a high-speed homogenization method, NLC was formulated variables were optimized by Box-Behnken statistical design. The optimized formulation of BS-loaded NLCs was incorporated into the chitosan-based MNs to prepare NLC-loaded polymeric MNs (NLC-MNs) and evaluated using testosterone induced alopecia rats. The cumulative amount of ß-sitosterol associated with NLC- MN which penetrated the rat skin in-vitro was 3612.27 ± 120.81 µg/cm2, while from the NLC preparation was 2402.35 ± 162.5 µg/cm2. The steady state flux (Jss) of NLC-MN was significantly higher than that of the optimized NLC formulation (P < 0.05). Anagen/telogen ratio was significantly affected by NLC and NLC-MN, which was 2.22 ± 0.34, 1.24 ± 0.18 respectively compared to 0.26 ± 0.08 for animal group treated with testosterone. The reversal of androgen-induced hair loss in animals treated with ß-sitosterol was a sign of hair follicle dominance in the anagenic growth phase. However, NLC-MN delivery system has shown significant enhancement of hair growth in rats. From these experimental data, it can be concluded that NLC incorporated MN transdermal system have potential in effective treatment of androgenic alopecia.

Formulation and Characterization of O/W Nanoemulsions of Hemp Seed Oil for Protection from Steatohepatitis: Analysis of Hepatic Free Fatty Acids and Oxidation Markers.

Non-alcoholic steatohepatitis (NASH) is a common type of metabolic liver disease which is characterized by fatty changes associated with hepatocyte injury, lobular inflammation, and/or liver fibrosis. Nanoemulsions are kinetically stable colloidal systems characterized by small droplet size. Hemp seed oil is a natural oil derived from Cannabis sativa seeds. The current study was designed to formulate nanoemulsion preparations of hemp seed oil with promising enhanced biological activity against high fat (HF) diet induced NASH in rats. Four nanoemulsion formulas (NEFs) were formulated based on high-pressure homogenization technique and evaluated for droplet size, zeta potential (ZP), polydispersity index (PDI), electrical conductivity, pH, and viscosity, as well as the preparation stability. The best NEF was selected to perform an in vivo rat study; selection was based on the smallest droplet size and highest physical stability. Results showed that NEF#4 showed the best physiochemical characters among the other preparations. Twenty male rats were assigned to four groups as follows: normal, NASH control, NASH + hemp seed oil and NASH + hemp seed oil NEF4. The rats were tested for body weight (BWt) change, insulin resistance (IR) and hepatic pathology. The hemp seed NEF#4 protected against NASH progression in rats and decreased the % of BWt gain compared to the original Hemp seed oil. NEF#4 of Hemp seed oil showed greater protective activity against experimental NASH and IR in rats. Hence, we can consider the nanoemulsion preparations as a useful tool for enhancing the biological action of the hemp seed oil, and further studies are warranted for application of this technique for preparing natural oils aiming at enhancing their activities.

Isoliquiritigenin attenuates inflammation and modulates Nrf2/caspase-3 signalling in STZ-induced aortic injury.

OBJECTIVES: The current study provides evidence on the ameliorative impact of Isoliquiritigenin (ISL), a natural bioflavonoid isolated from licorice roots against diabetes mellitus (DM)-induced aortic injury in rats. METHODS: DM was induced in male Sprague-Dawley rats by single I.P. injection of STZ (50 mg/kg). ISL was administrated daily (20 mg/kg, orally) for 8 wks. KEY FINDINGS: Diabetic group showed a significant aortic injury with evidence of atherosclerotic lesions development. Daily ISL (20 mg/kg, orally) administration for 8 wks significantly restored aortic oxidative/antioxidative stress homeostasis via modulating NrF-2/Keap-1/HO-1. Moreover, ISL treatment restored aortic levels of IL-10 and dampened aortic levels of IL-6 and TNF-α. Caspase-3 expression significantly declined as well. Further, ISL treatment successfully suppressed aortic endothelin-1 (ET-1) expression and restored NO contents, eNOS immunostaining paralleled with retraction in atherosclerotic lesions development, and lipid deposition with histopathological architectural preservation and restoration of almost normal aortic thickness. CONCLUSION: ISL can be proposed to be an effective protective therapy to prevent progression of DM-induced vascular injury and to preserve aortic integrity.

Design, Synthesis, Anticancer Activity, and Solid Lipid Nanoparticle Formulation of Indole- and Benzimidazole-Based Compounds as Pro-Apoptotic Agents Targeting Bcl-2 Protein.

Cancer is a multifactorial disease necessitating identification of novel targets for its treatment. Inhibition of Bcl-2 for triggered pro-apoptotic signaling is considered a promising strategy for cancer treatment. Within the current work, we aimed to design and synthesize a new series of benzimidazole- and indole-based derivatives as inhibitors of Bcl-2 protein. The market pan-Bcl-2 inhibitor, obatoclax, was the lead framework compound for adopted structural modifications. The obatoclax's pyrrolylmethine linker was replaced with straight alkylamine or carboxyhydrazine methylene linkers providing the new compounds. This strategy permitted improved structural flexibility of synthesized compounds adopting favored maneuvers for better fitting at the Bcl-2 major hydrophobic pocket. Anti-cancer activity of the synthesized compounds was further investigated through MTT-cytotoxic assay, cell cycle analysis, RT-PCR, ELISA and DNA fragmentation. Cytotoxic results showed compounds 8a, 8b and 8c with promising cytotoxicity against MDA-MB-231/breast cancer cells (IC50 = 12.69 ± 0.84 to 12.83 ± 3.50 µM), while 8a and 8c depicted noticeable activities against A549/lung adenocarcinoma cells (IC50 = 23.05 ± 1.45 and 11.63 ± 2.57 µM, respectively). The signaling Bcl-2 inhibition pathway was confirmed by molecular docking where significant docking energies and interactions with key Bcl-2 pocket residues were depicted. Moreover, the top active compound, 8b, showed significant upregulated expression levels of pro-apoptotic/anti-apoptotic of genes; Bax, Bcl-2, caspase-3, -8, and -9 through RT-PCR assay. Improving the compound's pharmaceutical profile was undertaken by introducing 8b within drug-solid/lipid nanoparticle formulation prepared by hot melting homogenization technique and evaluated for encapsulation efficiency, particle size, and zeta potential. Significant improvement was seen at the compound's cytotoxic activity. In conclusion, 8b is introduced as a promising anti-cancer lead candidate that worth future fine-tuned lead optimization and development studies while exploring its potentiality through in-vivo preclinical investigation.

Effect of the Surfactant and Liquid Lipid Type in the Physico-chemical Characteristics of Beeswax-based Nanostructured Lipid Carrier (NLC) of Metformin.

BACKGROUND: Metformin (MF) is an antidiabetic drug that belongs to class III of the biopharmaceutical classification system (BCS) characterized by high solubility and low permeability. OBJECTIVE: The study aimed to prepare metformin as nanostructured lipid carriers (MF-NLCs) to control the drug release and enhance its permeability through the biological membrane. METHODS: 22 full factorial design was used to make the design of MF-NLCs formulations. MFNLCs were prepared by hot-melt homogenization-ultra sonication technique using beeswax as solid lipid in the presence of liquid lipid (either capryol 90 or oleic acid) and surfactant (either poloxamer 188 or tween 80). RESULTS: The entrapment efficiency (EE%) of MF-NLCs was ranged from 85.2±2.5 to 96.5±1.8%. The particle size was in the nanoscale (134.6±4.1 to 264.1±4.6 nm). The value of zeta potential has a negative value ranged from -25.6±1.1 to -39.4±0.9 mV. The PDI value was in the range of 0.253±0.01 to 0.496±0.02. The cumulative drug release was calculated for MF-NLCs and it was found that Q12h ranged from 90.5±1.7% for MF-NLC1 to 99.3±2.8 for MF-NLC4. Infra-red (IR) spectroscopy and differential scanning calorimetry (DSC) studies revealed the compatibility of the drug with other ingredients. MF-NLC4 was found to be the optimized formulation with the best responses. CONCLUSION: 22 full factorial design succeed to obtain an optimized formulation which controls the drug release and increases the drug penetration.

Tranilast ameliorated subchronic silver nanoparticles-induced cerebral toxicity in rats: Effect on TLR4/NLRP3 and Nrf-2.

Silver nanoparticles (AgNPs) are widely applied in various aspects of life. However, recent studies reported their potential toxicity both on environment and human health. The present study aimed to unravel the underlying molecular mechanisms involved in AgNPs-induced brain toxicity. Moreover, chemopreventive effect of tranilast, an analogue of tryptophan metabolite and a mast cell membrane stabilizer was evaluated. Thirty Sprague Dawley rats were enrolled equally into Normal control group, AgNPs-intoxicated group (50 mg/kg, 3 times/week) and tranilast (300 mg/kg, 3 times/week)+AgNPs group. AgNPs administration triggered brain oxidative stress as depicted by reduced Nrf-2 expression, decreased TAC and GSH as well as upregulated brain lipid peroxidation. The apparent brain oxidative damage was accompanied by elevated levels of inflammatory cytokines (IL-1ß, IL-6 and TNF-α). Moreover, brain levels of TLR4, NLRP3 and caspase-1 were up-regulated. Additionally, histological study indicated marked cellular injury in cerebrum and cerebellum specimens. This was concomitant with elevated serum CK activity and CK-BB level. On the other hand, tanilast administration remarkably alleviated AgNPs-induced brain toxicity. The present study shed the light on implication of TLR4/NLRP3 axis and NrF2 in AgNPs-induced brain toxicity. In addition, it explored the potential protective effect of tranilast on AgNPs-induced brain injury via antioxidant and anti-inflammatory efficacies.

Synthesis and Antitumor Activity of Doxycycline Polymeric Nanoparticles: Effect on Tumor Apoptosis in Solid Ehrlich Carcinoma.

OBJECTIVES: The aim of this study was to prepare doxycycline polymeric nanoparticles (DOXY-PNPs) with hope to enhance its chemotherapeutic potential against solid Ehrlich carcinoma (SEC). METHODS: Three DOXY-PNPs were formulated by nanoprecipitation method using hydroxypropyl methyl cellulose (HPMC) as a polymer. The prepared DOXY-PNPs were evaluated for the encapsulation efficiency (EE%), the drug loading capacity, particle size, zeta potential (ZP) and the in-vitro release for selection of the best formulation. PNP number 3 was selected for further biological testing based on the best pharmaceutical characters. PNP3 (5 and 10 mg/kg) was evaluated for the antitumor potential against SEC grown in female mice by measuring the tumor mass as well as the expression and immunohistochemical staining for the apoptosis markers; caspase 3 and BAX. RESULTS: The biological study documented the greatest reduction in tumor mass in mice treated with PNP3. Importantly, treatment with 5 mg/kg of DOXY-PNPs produced a similar chemotherapeutic effect to that produced by 10 mg/kg of free DOXY. Further, a significant elevation in mRNA expression and immunostaining for caspase 3 and BAX was detected in mice group treated with DOXY-PNPs. CONCLUSIONS: The DOXY-PNPs showed greater antitumor potential against SEC grown in mice and greater values for Spearman's correlation coefficients were detected when correlation with tumor mass or apoptosis markers was examined; this is in comparison to free DOXY. Hence, DOXY-PNPs should be tested in other tumor types to further determine the utility of the current technique in preparing chemotherapeutic agents and enhancing their properties.

Quality by Design for the Development and Analysis of Enhanced In-Situ Forming Vesicles for the Improvement of the Bioavailability of Fexofenadine HCl in Vitro and in Vivo.

Drug absorption from the gastrointestinal tract (GIT) is one of the major problems affecting the bioavailability of orally absorbed drugs. This work aims to enhance Fexofenadine HCl oral bioavailability in vivo, the drug used for allergic rhinitis. In this study, novel spray-dried lactose-based enhanced in situ forming vesicles were prepared using different absorption enhancer by the slurry method. Full factorial design was used to obtain an optimized formulation, while central composite design was used to develop economic, environment-friendly analysis method of Fexofenadine HCl in plasma of rabbits. The optimized formulation containing Capryol 90 as absorption enhancer has a mean particle size 202.6 ± 3.9 nm and zeta potential -31.6 ± 0.9 mV. It achieved high entrapment efficiency of the drug 73.7 ± 1.7% and rapid Q3h release reaches 71.5 ± 2.7%. The design-optimized HPLC assay method in rabbit plasma could separate Fexofenadine HCl from endogenous plasma compounds in less than 3.7 min. The pharmacokinetic study and the pharmacological effect of the fexofenadine-loaded optimized formulation showed a significant increase in blood concentration and significantly higher activity against compound 48/80 induced systemic anaphylaxis-like reactions in mice. Therefore, enhanced in situ forming vesicles were effective nanocarriers for the entrapment and delivery of Fexofenadine HCl.

Optimization of Thiolated Chitosan Nanoparticles for the Enhancement of in Vivo Hypoglycemic Efficacy of Sitagliptin in Streptozotocin-Induced Diabetic Rats.

Sitagliptin (SGN) is an antidiabetic drug used for treatment of diabetes mellitus type II. The objectives of this study were to formulate SGN in form of thiolated chitosan (TC) nanoparticles to enhance the mucoadhesion properties of SGN to the gastrointestinal tract, prolong drug release, decrease side effects, and enhance patient compliance. Seventeen batches of SGN-TC nanoparticles were designed by Box-Behnken design and prepared using the ionic gelation method using tripolyphosphate (TPP) as crosslinking agent. The prepared formulations were evaluated for particle size, entrapment efficiency %, and in vitro drug release. Based on the results of optimization, three formulations (F1-F3) were prepared with different drug polymer ratios (1:1, 1:2, and 1:3). The mucoadhesion study and in vivo hypoglycemic activity of three formulations were evaluated in comparison to free SGN in streptozotocin (STZ)-induced diabetic rats. The seventeen SGN-TC nanoparticles showed small particle sizes, high entrapment efficiency, and prolonged drug release. The concentration of TC polymers had highest effect on these responses. The percentage of SGN-TC nanoparticles adhered to tissue was increased and the release was prolonged as the concentration of TC polymer increased (F3 > F2 > F1). The hypoglycemic effect of SGN-TC nanoparticles was significantly higher than resulted by free SGN. It was concluded that TC nanoparticles had the ability to enhance the mucoadhesion properties of SGN and prolong the drug release. SGN-TC nanoparticles significantly reduced plasma glucose levels compared to free SGN in STZ-induced diabetic rats.

Preparation and Evaluation of Carbamazepine Solid Lipid Nanoparticle for Alleviating Seizure Activity in Pentylenetetrazole-Kindled Mice.

Objectives: The study aimed to prepare carbamazepine in solid lipid nanoparticle form (CBZ-SLN) in order to enhance its anticonvulsant effect. Method: Eight formulations of CBZ-SLNs were prepared by homogenization and ultra-sonication techniques. Results: The prepared CBZ-SLN showed a high entrapment efficiency% (39.66 ± 2.42%-71.91 ± 1.21%), a small particle size (45.11 ± 6.72-760.7 ± 5.25 nm), and a negative zeta potential (from -21.5 ± 1.02 to -38.4 ± 1.32 mv). The in vitro release study showed the slow release of CBZ from SLNs compared to CBZ aqueous dispersion (p < 0.05). The infrared spectroscopy and the thermal analysis revealed the compatibility of the drug with other ingredients and the presence of drug in the more soluble amorphous estate, respectively. The in vivo study on mice revealed that the CBZ-SLN had a higher anticonvulsant efficacy than CBZ aqueous dispersion after a lethal and chronic dose of pentylenetetrazole (PTZ) (p < 0.05). The histopathological examination of the hippocampus revealed a decrease in the percentage of degeneration in mice treated with the CBZ-SLN compared to the PTZ and CBZ groups. Conclusion: CBZ can be formulated as SLN with higher anticonvulsant activity than free CBZ aqueous dispersion.