• Gravesen Frank posted an update 6 months ago

    The available treatments are not promising in reducing the recurrent rate of keloids as there are chances of high re-occurrences with similar/larger lesions on the removed keloid site. In this review, we are discussing the importance of controlled angiogenesis with the help of controlled drug delivery strategies enabling the wound healing process without the induction of keloid.Conjugation of recombinant human deoxyribonuclease I (rhDNase) to polyethylene glycol (PEG) of 20 to 40 kDa was previously shown to prolong the residence time of rhDNase in the lungs of mice after pulmonary delivery while preserving its full enzymatic activity. This work aimed to study the fate of native and PEGylated rhDNase in the lungs and to elucidate their biodistribution and elimination pathways after intratracheal instillation in mice. In vivo fluorescence imaging revealed that PEG30 kDa-conjugated rhDNase (PEG30-rhDNase) was retained in mouse lungs for a significantly longer period of time than native rhDNase (12 days vs 5 days). Confocal microscopy confirmed the presence of PEGylated rhDNase in lung airspaces for at least 7 days. In contrast, the unconjugated rhDNase was cleared from the lung lumina within 24 h and was only found in lung parenchyma and alveolar macrophages thereafter. Systemic absorption of intact rhDNase and PEG30-rhDNase was observed. However, this was significantly lower for the latter. Catabolism, primarily in the lungs and secondarily systemically followed by renal excretion of byproducts were the predominant elimination pathways for both native and PEGylated rhDNase. Catabolism was nevertheless more extensive for the native protein. On the other hand, mucociliary clearance appeared to play a less prominent role in the clearance of those proteins after pulmonary delivery. The prolonged presence of PEGylated rhDNase in lung airspaces appears ideal for its mucolytic action in patients with cystic fibrosis.The application of nanocarriers as drug delivery system for chemotherapeutic drugs has become a research hotspot in cancer treatment. Chemotherapy with high tumor-targeting accuracy and drug release specificity is the key to improve the efficacy of tumor chemotherapy and reduce the side effects caused by repeated doses drugs. Here, we synthesized a redox-sensitive nano-micelle formed by hyaluronic acid (HA) conjugated with d-α-tocopherol succinate (TOS) using a disulfide bond as the linker (HA-SS-TOS, HSST), which could actively accumulate to the tumor sites and metastasis cancer cells with high expression of CD44. The micelles could dissociate under the high GSH level in cancer cells, triggering a release of paclitaxel (PTX). Surprisingly, the precise chemotherapy instead induced a suppressive tendency of immune system, manifested by a significant increase in TGF-β, which weakened the therapeutic effect of micelles. Moreover, the high levels of TGF-β might be related to the increased drug-resistance of cancer cells. Research has shown that PD-1 pathway blockade can result in reduction in TGF-β expression, thus, a PLGA microsphere encapsulating PD-1 antagonist peptides A12 (A12@PLGA) was further prepared to activate the host immune response. Our data indicated that PTX-loaded HSST could accurately “find” the tumors as well as metastasis cancer cells, and efficiently kill most of them. The joining of a durable PD-1 blockage significantly boosted the efficacy of PTX@HSST on multiple tumor models, including lung metastatic tumors and even multidrug-resistant tumors. Thus, our work presented an optimal chemo-immunotherapy combined system, which shows profound significance for future cancer therapy in clinic.Microbial exopolysaccharides (EPSs) exhibit diverse functionalities and offer a variety of structural options that can be altered to fit a specific purpose. EPSs can degrade within the body via biological processes, and polysaccharides are regarded as generally safe. More so, microbial EPS is replicable from several known, inexpensive, and plentiful sources. Drug delivery-related research involving polysaccharides have continuously cited minimal to zero cytotoxicity and, where tested, sufficient drug release and a competent release profile. Transdermal drug delivery systems as films not only avoids first-pass metabolism, but also provides pain-free administration, assists patients with dysphagia, has increased patient compliance, can be self-administered, and can be removed at any time. Commonly used synthetic polymers in the field of drug delivery have been related to problems regarding toxicity and immunogenicity, escalating the need for an alternative. Ultimately, the risks while using synthetic polymers could result in serious negative influences involving physiological, physiochemical, and molecular events. Research involving exopolysaccharides from extremophiles is only recently gaining attention. However, commercial use of microbial polysaccharides in other areas as well as the positive results from preliminary research suggests microbial EPSs have a promising future in biomedical engineering and medicine, especially as an alternative to current synthetic polymers.Therapeutic strategies based on antisense oligonucleotides and therapeutic genes are being extensively investigated for the treatment of hereditary muscle diseases and hold great promise. However, the cellular uptake of these polyanions to the muscle cells is inefficient. https://www.selleckchem.com/products/tiplaxtinin-pai-039.html Therefore, it is necessary to develop more effective methods of gene delivery into the muscle tissue. The A2G80 peptide (VQLRNGFPYFSY) from the laminin α2 chain has high affinity for α-dystroglycan (α-DG) which is expressed on the membrane of muscle cells. In this study, we designed a peptide-modified A2G80 with oligoarginine and oligohistidine (A2G80-R9-H8), and prepared peptide/plasmid DNA (pDNA) complex, to develop an efficient gene delivery system for the muscle tissue. The peptide/pDNA complex showed α-DG-dependent cellular uptake of the A2G80 sequence and significantly improved gene transfection efficiency mediated by the oligohistidine sequence in C2C12 myoblast cells. Further, the peptide/pDNA complex promoted efficient and sustained gene expression in the Duchenne muscular dystrophy mouse models.

All content contained on CatsWannaBeCats.Com, unless otherwise acknowledged,is the property of CatsWannaBeCats.Com and subject to copyright.

CONTACT US

We're not around right now. But you can send us an email and we'll get back to you, asap.

Sending

Log in with your credentials

or    

Forgot your details?

Create Account