Drug Development and Industrial Pharmacy最新文献

Objective: BCS class III drug (highly soluble, poorly permeable) possesses low oral bioavailability. The research work highlights the utility of self-double emulsifying drug delivery system (SDEDDS) which are stable isotropic mixture of w/o primary emulsion and hydrophilic surfactants for improving oral bioavailability of Ca-DTPA (Calcium diethylenetriamine pentaacetate). Upon oral administration, SDEDDS rapidly emulsifies into w/o/w double emulsions in the aqueous gastrointestinal environment, with hydrophilic drugs entrapped inside oil reservoirs.

Methods: SDEDDS formulation was successfully developed using excipients, that is, medium chain triglycerides, oleic acid, phospholipids, Span 80, Tween 80 using double emulsification technique.

Results: The optimized formulation F4 (Aq. phase: 11.6%w,w; MCT & oleic acid: 70.9%w/w; Span 80:17.5%w/w; Lecithin:16%w/w and Tween 80 (10%w/w)) appeared bright yellow liquid which upon dilution appeared milky white within 2 min, droplet size (501.7 nm), pdi value (0.044), zeta potential (-52 mV), entrapment efficiency (79.6 ± 1.63), viscosity (72.2 ± 1.8 mpA.s), significant high cumulative in vitro drug permeation (CDP) and 2.17-fold increase in apparent permeability coefficient. Pharmacokinetic studies in rats showed 1.17-fold increases in AUC of F4 and comparatively higher plasma levels (C_max) compared with pure drug administered orally. The Absolute (OF4, OD) and Relative bioavailability was found to be 14.52%, 12.35%, and 117.47%, respectively.

Conclusion: The present studies have clearly demonstrated that SDEDDS could readily form w/o/w double emulsions in vivo with enhanced in vitro and in vivo oral bioavailability. Therefore, considerable augmentation in the rate and extent of oral drug absorption ratified the better performance of the SDEDDS in enhancing the bioavailability of Ca-DTPA.

Objective: Non-tricyclic antidepressants (non-TCAs) work by preventing the intake of norepinephrine and serotonin. Therefore, the aim of this study was to identify a potent non-TCAs and to develop liposomal formulation, characterize and to determine the drug release study across model of dialysis membrane via in vitro and in silico techniques.

Methods: The in silico docking analysis identified venlafaxine (VLF) as the best non-TCAs with the depressant targets (PDB ID: 3PBL and 4BVN). VLF-loaded liposomal formulation was prepared by the thin-film hydration technique and characterized by physicochemical properties, including entrapment efficacy, in vitro drug release, particle size analysis, and FTIR. Moreover, this article also compares VLF and VLF-loaded with liposome carriers (LPs) based on nose-to-brain drug delivery approaches to treating depression.

Results: Drug release profiles of the optimal liposomal formulation of VLF-LPs were examined in the high entrapment efficiency 94.13 ± 1.20% was attained at 224 nm, composed of spherical particles having a mean particle size of 191 ± 2.0 nm, a polydispersity index of 0.281 ± 0.06 and zeta potential of -20.3 mV. The best formulation of VLF-LPs was more effective than oral VLF treatment, as shown by the in vitro drug release data.

Conclusion: The results show that the VLF-LPs formulation is a promising potential platform for application in nose-to-brain drug delivery. Thus, highlighting the robustness of the intranasal drug delivery system with enhanced pharmaceutical properties, efficacy, and bioavailability for the anti-depression effect.

Object: We report the preparation, characterization, and in-vitro therapeutic evaluation of Metformin-Loaded, Transferrin-Poloxamer-Functionalized Chitosan Nanoparticles (TPMC-NPs) for their repurposing in Alzheimer's disease (AD).

Significance: Usefulness of this work to establish the repurposing of metformin for the treatment of AD.

Methods: The TPMC-NPs were prepared by ionic gelation method using sodium tripolyphosphate. The modification and functionalization were confirmed by FTIR and ¹H^-NMR spectroscopy. The physicochemical characterization was performed using DLS, FTIR,¹H-NMR, CD spectroscopy, SEM, DSC, PXRD, HR-TEM, and hot-stage microscopy.

Results: The size, PDI, percent entrapment efficiency, and percent drug loading of TPMC-NPs were found to be 287.4 ± 9.5, 0.273 ± 0.067, 81.15 ± 7.17%, 11.75%±8.21%, respectively. Electron microscope analysis revealed smooth and spherical morphology. The transferrin conjugation efficiency was found to be 46% by the BCA method. CD spectroscopy confirmed no significant loss of the secondary structure of transferrin after conjugation. PXRD data indicated the amorphous nature of the TPMC-NPs. Hot-stage microscopy and DSC confirmed the thermal stability of TPMC-NPs. The in-vitro drug release showed a sustained release at pH 7.4. The DPPH assay displayed 80% antioxidant activity of TPMC-NPs in comparison with metformin and blank NPs. The in-vitro cytotoxicity assay revealed 69.60% viable SH- SY5Y cells at 100 µg/mL of TPMC NPs. The ex-vivo nasal ciliotoxicity and mucoadhesion studies showed no significant toxicity, and 98.16% adhesion, respectively. The nasal permeability study showed the release of metformin within 30 min from TPMC-NPs.

Conclusion: The obtained results suggested the usefulness of TPMC-NPs in the treatment of AD via the intranasal route.

Introduction: Bacterial infections caused by different strains of bacteria still one of the most important disorders affecting humans worldwide. Polymers nanocomposite systems could be considered as an alternative to conventional antibiotics to eradicate bacterial infections.

Significance: In an attempt to enhance the antibacterial performance of silver and iron oxide nanoparticles, decrease their aggregation and toxicity, a polymeric hybrid nanocomposite system combining both nanoparticles is produced.

Methods: Magnetic Ag-Fe₃O₄@polymer hybrid nanocomposites prepared using different polymers, namely polyethylene glycol 4000, ethyl cellulose, and chitosan were synthesized via wet impregnation and ball-milling techniques. The produced nanocomposites were tested for their physical properties and antibacterial activities.

Results: XRD, FT-IR, VSM, and TEM results confirmed the successful preparation of hybrid nanocomposites. Hybrid nanocomposites have average crystallite sizes in the following order Ag-Fe₃O₄@CS (8.9 nm) < Ag-Fe₃O₄@EC (9.0 nm) < Ag-Fe₃O₄@PEG4000 (9.4 nm) and active surface area of this trend Ag-Fe₃O₄@CS (130.4 m²g^-1) > Ag-Fe₃O₄@EC (128.9 m²g^-1) > Ag-Fe₃O₄@PEG4000 (123.4 m²g^-1). In addition, they have a saturation magnetization in this order: Ag-Fe₃O₄@PEG4000 (44.82 emu/g) > Ag-Fe₃O₄@EC (40.14 emu/g) > Ag-Fe₃O₄@CS (22.90 emu/g). Hybrid nanocomposites have a pronounced antibacterial action against Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus intermedius compared to iron oxide nanoparticles and positive antibacterial drug. In addition, both Ag-Fe₃O₄@EC and Ag-Fe₃O₄@CS have a lower MIC values compared to Ag-Fe₃O₄@PEG and positive control.

Conclusion: Magnetic Ag-Fe₃O₄ hybrid nanocomposites could be promising antibacterial nanomaterials and could pave the way for the development of new materials with even more unique properties and applications.