Drug Delivery最新文献

Due to the lack of safe, effective, and gene-targeted delivery technology. In this study, we have prepared nanobubbles loaded PDLIM5 siRNA (PDLIM5siRNA-NBs) to investigate the transfection efficiency and their antagonism in drug resistance in combination with ultrasound irradiation for non-small-cell lung cancer (NSCLC). Research results show that the PDLIM5 siRNA are effectively bound to the shell of NBs with a mean diameter of 191.6 ± 0.50 nm and a Zeta potential of 11.8 ± 0.68 mV. And the ultrasonic imaging indicated that the PDLIM5 siRNA NBs maintain the same signals as the microbubbles (SonoVue). Under the optimized conditions of 0.5 W/m² ultrasound intensity and 1 min irradiation duration, the highest transfection efficiency of PC9GR cells was 90.23 ± 1.45%, which resulted in the inhibition of PDLIM5 mRNA and protein expression. More importantly, the anti-tumor effect of fabricated PDLIM5siRNA-NBs with the help of ultrasound irradiation has been demonstrated to significantly inhibit tumor cell growth and promote apoptosis. Therefore, NBs carrying PDLIM5siRNA may have the potential to act as gene vectors combined with ultrasound irradiation to antagonize drug resistance for NSCLC.

Effective chemotherapy for clinical treatment of brain diseases is still lacking due to the poor penetration of the blood-brain barrier (BBB). The aim of this study was to construct a folate modified pterostilbene (Pt) loaded polymeric micellar delivery system (F-Pt/M) with mPEG-PCL as carrier material to aim at penetrating the BBB for brain tissue targeting via receptor-mediated endocytosis. In this study, F-Pt/M was prepared using thin-film hydration method and then optimized by response surface methodology (RSM) with the entrapment efficiency (EE), drug loading (DL) and hydrodynamic diameter (HD) as indexes. The average hydrodynamic diameter and zeta potential of optimal F-Pt/M were 133.2 nm and 24.6 mV, respectively. DL (18.3%) and EE (98.6%) made the solubility of Pt in water about 25 times higher than that of crude Pt. Results of DSC evaluation revealed that drugs were successfully encapsulated inside the polymeric micelles. TEM images showed that homogeneous spherical micellar structures with a narrow size distribution were developed. The release result in vitro showed that F-Pt/M presented sustained release behavior compared to control free Pt solution. Compared to non-targeted Pt/M, F-Pt/M had a significantly higher cytotoxicity against FR-overexpressing A172 cells. In vitro cellular uptake tests illustrated that the micellar delivery system could significantly improve the accumulation of drugs in target cells via receptor-mediated endocytosis. BBB penetration value (P) of F-Pt/M was about 4 folds higher than that of free Pt group. In addition, drug targeting index (DTI) was calculated to determine targeting of F-Pt/M to the brain which was found to be 4.89, implying improved brain targeting was achieved. Hence, the developed F-Pt/M exhibited great potential for delivering more drug molecules across the BBB for the treatment of brain diseases.

Diabetes mellitus is one of the most concerning conditions, and its chronic consequences are almost always accompanied by infection, oxidative stress, and inflammation. Reducing excessive reactive oxygen species and the wound's inflammatory response is a necessary treatment during the acute inflammatory phase of diabetic wound healing. Malva sylvestris extract (MS) containing nanofibers containing neomycin sulfate (NS) were synthesized for this investigation, and their impact on the healing process of diabetic wounds was assessed. Using Design Expert, the electrospinning process for the fabrication of NS nanofibers (NS-NF) was adjusted for applied voltage (X₁), the distance between the needle's tip and the collector (X₂), and the feed rate (X₃) for attaining desired entrapment efficacy [EE] and average nanofiber diameter (ND). The optimal formulation can be prepared with 19.11 kV of voltage, 20 cm of distance, and a flow rate of 0.502 mL/h utilizing the desirability approach. All the selected parameters and responses have their impact on drug delivery from nanofibers. In addition, M. sylvestris extracts have been added into the optimal formulation [MS-NS-NF] and assessed for their surface morphology, tensile strength, water absorption potential, and in vitro drug release studies. The NS and MS delivery from MS-NS-NF has been extended for more than 60 h. M. sylvestris-loaded nanofibers demonstrated superior antibacterial activity compared to plain NS nanofibers. The scaffolds featured a broad aspect and a highly linked porous fibrous network structure. Histomorphometry study and the in vitro scratch assay demonstrate the formulation's efficacy in treating diabetic wound healing. The cells treated with MS-NS-NF in vivo demonstrated that wound dressings successfully reduced both acute and chronic inflammations. To improve the healing of diabetic wounds, MS-NS-NF may be regarded as an appropriate candidate for wound dressing.

Overdosage of antibiotics used to prevent bacterial infections in the human and animal gastrointestinal tract would result in disturbing of intestinal barrier, significant misbalancing effects of intestinal microflora and persuading bacterial resistance. The main objective of the present investigation is to design and develop novel combinations of organic curcumin (Cur) and antimicrobial peptide (Amp) loaded chitosan nanoformulations (Cur/Amp@CS NPs) to improve significant effects on antibacterial action, immune response, intestine morphology, and intentional microflora. The antibacterial efficiency of the prepared nanoformulations was evaluated using Escherichia coli (E. coli) induced bacterial infections in GUT of Rat models. Further, we studied the cytocompatibility, inflammatory responses, α-diversity, intestinal morphology, and immune responses of treated nanoformulations in rat GUT models. The results indicated that Cur/Amp@CS NPs are greatly beneficial for intestinal microflora and could be a prodigious alternative of antibiotics.

Based on the administration convenience, transmucosal buccal drug delivery allows special strength points over peroral routes for systemic delivery. It could achieve local or systemic effect and boost drugs' bioavailability for agents with first pass metabolism. The current study aimed to manufacture and optimize a lavender oil-based nanoemulsion loaded with zaleplon and incorporate it into fast-disintegrating tablets to promote its dissolution and oral bioavailability via oral mucosa. Zaleplon-loaded nanoemulsions were devised with various levels of lavender oil (10% to 25%), the surfactant Sorbeth-20 (35% to 65%), and the co-surfactant HCO-60 (20% to 40%); the extreme vertices mixture statistical design was adopted. The droplet size and drug-loading efficiency were the evaluated. The optimal formulation was transformed into self-nanoemulsified lyophilized tablets (ZP-LV-SNELTs), which were tested for their uniformity of content, friability, and disintegration time with in-vitro release. Finally, the pharmacokinetic parameters of the ZP-LV-SNELTs were determined and compared with those of marketed formulations. The optimal nanoemulsion had a droplet size of 87 nm and drug-loading capacity of 185 mg/mL. ZP-LV-SNELTs exhibited acceptable friability and weight uniformity and a short disintegration time. The in-vitro release of ZP-LV-SNELTs was 17 times faster than that of the marketed tablet. Moreover, the optimal ZP-LV-SNELTs increased the bioavailability of zaleplon in rabbits by 1.6-fold compared with the commercial tablets. Hence, this investigation revealed that ZP-LV-SNELTs delivered zaleplon with enhanced solubility, a fast release, and boosted bioavailability thru oral mucosa which provided a favorable route for drug administration which is suggested to be clinically investigated in future studies.

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi's diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm²) than LNCs (12.7 ± 1.52 µg/cm²). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.

Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size. To compare the efficiency of Dex-SP and dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography-mass spectrometry. The dexamethasone nanosuspensions resulted in significantly higher drug concentrations in perilymph and cochlear tissues than Dex-SP at 6 h; interestingly, animals treated with nanosuspensions showed a 26-fold higher dexamethasone concentrations in their cochlear tissues than animals treated with Dex-SP. In addition, dexamethasone nanosuspension caused better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo, and in the ototoxic animal model, the nanosuspension showed a significantly better hearing-protective effect against ototoxic drugs than Dex-SP. In the in vivo safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL. In conclusion, a nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection.

Glaucoma is the leading cause of irreversible vision loss worldwide, and reduction of intraocular pressure (IOP) is the only factor that can be interfered to delay disease progression. As the first line and preferred method to treat glaucoma, eye drops have many shortcomings, such as low bioavailability, poor patient compliance, and unsustainable therapeutic effect. In this study, a highly efficient brimonidine (BRI) silicone rubber implant (BRI@SR@TPU implant) has been designed, prepared, characterized, and administrated for sustained relief of IOP to treat glaucoma. The in vitro BRI release from BRI@SR@TPU implants shows a sustainable release profile for up to 35 d, with decreased burst release and increased immediate drug concentration. The carrier materials are not cytotoxic to human corneal epithelial cells and conjunctival epithelial cells, and show good biocompatibility, which can be safely administrated into rabbit's conjunctival sac. The BRI@SR@TPU implant sustainably released BRI and effectively reduced IOP for 18 d (72 times) compared to the commercial BRI eye drops (6 h). The BRI@SR@TPU implant is thus a promising noninvasive platform product for long-term IOP-reducing in patients with glaucoma and ocular hypertension.

The treatment of bone metastatsis as primary bone cancer itself is still a challenge. The use od radium dichloride ([²²³Ra] RaCl₂) has emerged in the last few years as one of the best treatment choice for bone cancer, with especial focus in bone metastasis. The alpha-emitter radiopharmaceutical has showed potent and efficient results in several clinical trials. In this study we have formulated radium dichloride ([²²³Ra] RaCl₂) nanomicelles in order to evaluate and compare with pure radium dichloride ([²²³Ra] RaCl₂). The results showed that nanomicelles at the same dose had a superior effect (20% higher efficient) when compared with pure radium dichloride ([²²³Ra] RaCl₂). The results corroborated the effectiveness of the nanosystem validating the application of nanotechnology in alpha-radiotherapy with radium dichloride ([²²³Ra] RaCl₂).