• Skov Conradsen posted an update 6 hours, 57 minutes ago

    Bacterial cellulose nanofibrils (BCNFs), possessing excellent biocompatibility as well as hygroscopicity, are receiving high interest as a biomaterial for biomedical and healthcare treatments, since they exert various interactions with tissues after surface modification with biochemicals such as peptides, proteins, and catechols. Herein, we report a BCNF-based skin adhesion system, wherein cell penetrating peptide (CPP)-conjugated BCNFs were employed to enhance the attraction to the skin under wet conditions. For this, we conjugated Bac7, a type of CPP, with the carboxylate of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized BCNFs. We showed that Bac7-conjugated BCNFs exhibited both hydrophobic and electrostatic interactions with the cell membrane, which eventually led to the remarkable adhesion against the skin surface. Furthermore, we demonstrated that such tailored skin attraction played a key role in improving skin water retention.Mesenchymal stem cells (MSCs) have recently emerged as a promising living carrier for targeted drug delivery. A wealth of literature has shown evidence for great advances in MSCs-based drug delivery system (MSCs-DDS) in the treatment of various diseases. Nevertheless, as this field of study rapidly advances, several challenges associated with this delivery strategy have arisen, mainly due to the inherent limitations of MSCs. To this end, several novel technologies are being developed in parallel to improve the efficiency or safety of this system. In this review, we introduce recent advances and summarize the present challenges of MSCs-DDS. We also highlight some potential technologies to improve MSCs-DDS, including nanotechnology, genome engineering technology, and biomimetic technology. Finally, prospects for application of artificially improved MSCs-DDS are addressed. The technologies summarized in this review provide a general guideline for the improvement of MSCs-DDS.The main aim is to develop transcutaneous tenoxicam (TNX) loaded vesicles to control osteoarthritis (OA) without common side effects. Different vesicles were prepared by the emulsification technique, where poloxamer and glyceryl monooleate used for cubosomes. Then, hyalcubosomes were prepared by adding sodium hyaluronate to cubosomes components. Different characterization techniques were used. The selected formulations were tested using an ex-vivo permeation study to evaluate the ability to penetrate and retained in skin layers. Also, in-vitro cell studies using human skin fibroblasts were evaluated the safety of the formulation. The anti-inflammatory efficiency was tested using an in-vivo carrageenan-induced rat paw edema model. Finally, the efficiency to control OA symptoms was tested on three patients with a medical history of knee OA. Results confirmed the successful development of spherical cubosomes with particle size 90%). Moreover, the addition of sodium hyaluronate to selected cubosomes improved viscosity and spreadability. Permeation study confirmed drug penetration and deposition. Cell studies proved the safety of the selected formulation. The animal model showed high anti-inflammatory activity. Finally, the preliminary clinical study demonstrates the potential efficacy and safety of the formulation in controlling OA symptoms over 8 weeks of therapy.Natamycin is the only FDA approved drug that is used as a first line of treatment for fungal keratitis caused by filamentous fungi, however natamycin is known for poor corneal penetration. Cell penetrating peptides (CPPs) are emerging nanocarriers for the enhanced delivery of various macromolecules owing to their distinct cellular translocation ability. In the present study, tissue penetration ability and antifungal efficacy of CPP (Tat2) conjugated natamycin has been investigated and compared with natamycin alone in vivo. selleck chemical Results show that Tat2natamycin exhibits five- fold higher ocular penetration than natamycin alone when given topically. Complete resolution of fungal keratitis in 44% of the animals in Tat2natamycin treated group as compared to only 13% of the animals in natamycin treated group further highlights its increased antifungal efficacy. Hence, this conjugate is a promising antifungal molecule with enhanced ocular penetration as well as antifungal efficacy against selected fungal species.

    Numerous oral treatment options have been reported for neurological disorders, especially Alzheimer’s disease (AD). Galantamine (GAL) is one of such drugs duly approved for management of AD. However, it exhibits poor brain penetration, low intestinal permeation and requires frequent dosing in AD treatment. The present studies, accordingly, were undertaken to develop DSPE-PEG 2000-based micelles loaded with GAL for efficient brain uptake, improved and extended pharmacokinetics, along with reduced dosing regimen.

    Mixed nanomicelles (MNMs) were systematically formulated using QbD approach, and characterized for morphology, entrapment efficiency andin vitrodrug release.

    Studies on CaCo-2 and neuronal U-87 cell lines exhibited substantial enhancement in the cellular permeability and uptake of the developed MNMs. Pharmacokinetic studies performed on rats showed significantly improved values of plasma AUC (i.e., 2.28-fold, p<0.001), ostensibly due to bypassing of hepatic first-pass metabolism and improved intestinal permeability, together with significant rise in MRT (2.08-fold, p<0.001) and t

    (4.80-fold; p<0.001) values, indicating immense potential for prolonged drug residence in body.Besides, substantial elevation in brain drug levels, distinctly improved levels of biochemical parameters in brain homogenates and cognitive improvement in β-amyloid-treated rats, testify the superiority in MNMs in therapeutic management of AD.

    The preclinical findings of the developed nanocarrier systems successfully demonstrate the notable potential of enhanced drug efficacy, extended duration of action and improved patient compliance.

    The preclinical findings of the developed nanocarrier systems successfully demonstrate the notable potential of enhanced drug efficacy, extended duration of action and improved patient compliance.