Nano/microfibrous polymeric constructs present various inherent advantages, such as highly porous architecture and high surface to volume ratio, making them attractive for tissue engineering purposes. Electrospinning is the most preferred technique for the fabrication of polymeric nanofibrous assemblies that can mimic the physical functions of native extracellular matrix greatly favoring cells attachment and thus influencing their morphology and activities. Different approaches have been developed to apply polymeric microfiber fabrication techniques (e.g. wet-spinning) for the obtainment of scaffolds with a three-dimensional network of micropores suitable for effective cells migration. Progress in additive manufacturing technology has led to the development of complex scaffold's shapes and microfibrous structures with a high degree of automation, good accuracy and reproducibility. Various loading methods, such as direct blending, coaxial electrospinning and microparticles incorporation, are enabling to develop customized strategies for the biofunctionalization of nano/microfibrous scaffolds with a tailored kinetics of release of different bioactive agents, ranging from small molecules, such as antibiotics, to protein drugs, such as growth factors, and even cells. Recent activities on the combination of different processing techniques and loading methods for the obtainment of biofunctionalized polymeric constructs with a complex multiscale structure open new possibilities for the development of biomimetic scaffolds endowed with a hierarchical architecture and a sophisticated release kinetics of different bioactive agents. This review is aimed at summarizing current advances in technologies and methods for manufacturing nano/microfibrous polymeric constructs suitable as tissue engineering scaffolds, and for their combination with different bioactive agents to promote tissue regeneration and therapeutic effects.
Pirarubicin (THP) is an effective anthracycline for the treatment of solid tumor. However, its potential side effects are prominent and clinical use is restricted. We aimed to develop a novel pirarubicin-oleic acid complex albumin nanoparticle (THP-OA-AN) in order to reduce the toxicity of THP. Oleic acid, human serum albumin (HSA), and egg yolk lecithin E80 was used to prepare THP-OA-AN. Prepared THP-OA-AN was characterized and animal experiments were conducted to assess its tumor suppression effect, distribution, and toxicity. Comparison between THP and THP-OA-AN showed that, with retained antitumor efficiency, the toxicity of THP-OA-AN is significantly reduced regarding bone marrow suppression, cardiotoxicity, renal toxicity, and gastrointestinal toxicity. This study developed a safe and effective formulation of THP, which has greater potential for clinic use in the tumor therapy.
A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N-terminal myristoylated preS1/21-47 (preS1/21-47(myr)) of hepatitis B virus was successfully developed. The study aimed to elucidate the cellular uptake mechanism of preS1/21-47(myr) modified PEG-Lip (preS1/21-47(myr)-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47(myr)-PEG-Lip in Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47(myr)-PEG-Lip was effectively taken up by hepatogenic cells (including primary hepatocytes and liver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing mice, preS1/21-47(myr)-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47(myr)-PEG-Lip in hepatic tumor. Furthermore, the antitumor effect of preS1/21-47(myr)-PEG-Lip loaded with paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation, no acute systemic toxicity and immunotoxicity were observed after intravenous injection of preS1/21-47(myr)-PEG-Lip. No liver toxicity was observed despite the dramatic increase of preS1/21-47(myr)-PEG-Lip in liver. Taken together, preS1/21-47(myr)-PEG-Lip represents a promising carrier system for targeted liver disease therapy and imaging.
7-Ethyl-10-hydroxy-camptothecin (SN38), the active metabolite of irinotecan (CPT-11), is an effective antineoplastic agent against many malignancies. Although it is 100-fold to 1000-fold more potent than CPT-11, the clinical utility of SN38 has been extremely restricted because of its poor solubility in any pharmaceutically acceptable solvents. The aim of this study was to develop SN38 nanoparticles (SN38-PC-LNs) using pharmaceutically acceptable excipients, and investigate the therapeutic efficacies in vitro and in vivo. SN38-phospholipid complex (SN38-PC) was prepared and loaded into lipid nanoparticles. The particle size was approximately 200 nm with a narrow size distribution. A high encapsulation efficiency of 88.11% ± 1.41% and drug loading of 9.55% ± 0.84% were achieved under the optimal condition. SN38-PC-LNs exhibited potent cytotoxic effects against a panel of human tumor cell lines (HT-29, HepG2, A549 and MCF-7). In vivo evaluation proved the enhanced antitumor efficacy of SN38-PC-LNs in mice bearing S180 tumor as well. The results from this study demonstrated an effective formulation of SN38 has been developed, which is promising for the delivery of SN38 for tumor chemotherapy.
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