ABSTRACT
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ABSTRACT
In this study, we developed novel hyaluronic acid cross-linked zein nanogels (HA-Zein NGs) to deliver the potential anticancer agent curcumin (CRC), a naturally occurring phytochemical drug in cancer cells. In vitro studies showed that they are highly compatible with the tested cell lines. They showed CD44 specific uptake in CT26 cell line more than by the CD44 receptor pre-inhibited CT26 cells. The CRC encapsulated HA-Zein NGs (HA-Zein-CRC NGs) found to exert a specific toxicity against CT26 sparing healthy normal fibroblast cells in vitro. The apoptotic effects were further confirmed with flow cytometry showing that the HA-Zein-CRC NGs exhibited high anticancer activity against the CT26 cells. The in vivo bio-distribution with a CT26 tumor model showed their high tumor accumulation thereby improved antitumor efficacy with a low dosage of CRC, compared to the previous reports. Thus, the preclinical studies clearly showed that these novel HA-Zein NGs would be highly beneficial in encapsulating hydrophobic drugs with improved pharmacokinetics thereby enhancing the therapeutic outcomes.
Subject(s)
Curcumin/chemistry , Drug Carriers/chemistry , Hyaluronan Receptors/metabolism , Hyaluronic Acid/chemistry , Nanoparticles/chemistry , Zein/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Biocompatible Materials/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Cross-Linking Reagents/chemistry , Curcumin/therapeutic use , Drug Liberation , Drug Stability , Humans , Hydrophobic and Hydrophilic Interactions , Mice, Inbred BALB C , Molecular Targeted Therapy/methods , Polymerization , Tissue DistributionABSTRACT
This work aimed at formulating paclitaxel (PTX) loaded cell penetrating peptide (CPP) coated Mn doped ZnS nanoparticles (Mn:ZnS NPs) for improved anti-cancer efficacy in vitro and in vivo. The developed PTX loaded Mn:ZnS NPs with different CPPs (PEN, pVEC and R9) showed enhanced anti-cancer effect compared to bare PTX, which has been validated by MTT assay followed by apoptosis assay and DNA fragmentation analysis. The in vivo bio-distribution and anti-cancer efficacy was studied on breast cancer xenograft model showing maximum tumor localization and enhanced therapeutic efficacy with R9 coated Mn:ZnS NPs (R9:Mn:ZnS NPs) and was confirmed by H/E staining. Thus, R9:Mn:ZnS NPs could be an ideal theranostic nano-carrier for PTX with enhanced the rapeutic efficacy toward cancer cells, where penetration and sustainability of therapeutics are essential.
Subject(s)
Cell-Penetrating Peptides/chemistry , Cell-Penetrating Peptides/pharmacology , Manganese/chemistry , Nanoparticles/chemistry , Paclitaxel/chemistry , Paclitaxel/pharmacology , Sulfides/chemistry , Zinc Compounds/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Carriers/chemistry , Female , HeLa Cells , Humans , Polyethylene Glycols/chemistry , Polymers/chemistryABSTRACT
INTRODUCTION: The skin, as the largest organ, is a better option for drug delivery in many diseases. However, most transdermal delivery is difficult due to the low permeability of therapeutics across the various skin layers. There have been many innovations in transdermal drug delivery to enhance the therapeutic efficacy of the drugs administered. Microneedles (MN), micron sized needles, are of great interest to scientists as a new therapeutic vehicle through transdermal routes, especially for vaccines, drugs, small molecules, etc. AREAS COVERED: This review covers new insights into different types of MNs such as solid, hollow, coated and dissolving MNs (SMNs, HMNs, CMNs, and DMNs) for selected biomedical applications in detail. Specific focus has been given to CMNs and DMNs for vaccine and drug delivery applications with recent developments in new MNs covered. EXPERT OPINION: This review explores the feasibility of innovative MNs used as a drug delivery carrier. Because most of the SMNs and HMNs have many limitations, it is difficult to achieve therapeutic efficacy. Therefore, many scientists are investigating functional modifications of MNs through covalent and non-covalent methods, especially for CMNs and DMNs. The biomedical applications of MNs are growing and new exciting improvements could be achieved, thus resulting in better micro/nano technologies in the near future.
Subject(s)
Drug Delivery Systems/instrumentation , Microinjections/instrumentation , Needles , Vaccines/administration & dosage , Administration, Cutaneous , Nevus, Pigmented , Skin/metabolism , Skin Absorption , Skin NeoplasmsABSTRACT
Microneedles were initially developed as pretreatment tools for the delivery of therapeutic drugs to intradermal locales in the human skin. Over time, variations in microneedle forms and functions burgeoned through the works of many researchers worldwide. The four major types of microneedles in use today are solid, dissolving, coating, and hollow microneedles. The emergence of different types of microneedles also paved the way for a flourishing diversification of microneedle applications, one of the most remarkable of which deals with the transcutaneous delivery of prophylactic vaccines. Here, we describe fabrication methods of microneedles and DNA vaccine loading methods on the microneedle surface. Furthermore, in the latter part of this chapter, in vivo test protocols for assessing the efficacy of gene delivery using microneedles are described.
