Nanoparticle-based Drug Delivery Systems Research Articles

Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4) and a chemotherapeutic drug (doxorubicin) and conjugate with targeting molecules (iRGD peptide) for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors.

Delivery of drugs to intracellular organelles using drug delivery systems: Analysis of research trends and targeting efficiencies

Targeting of drug delivery systems (DDSs) to specific intracellular organelles (i.e., subcellular targeting) has been investigated in numerous publications, but targeting efficiency of these systems is seldom reported. We searched scientific publications in the subcellular DDS targeting field and analyzed targeting efficiency and major formulation parameters that affect it. We identified 77 scientific publications that matched the search criteria. In the majority of these studies nanoparticle-based DDSs were applied, while liposomes, quantum dots and conjugates were used less frequently. The nucleus was the most common intracellular target, followed by mitochondrion, endoplasmic reticulum and Golgi apparatus. In 65% of the publications, DDSs surface was decorated with specific targeting residues, but the efficiency of this surface decoration was not analyzed in predominant majority of the studies. Moreover, only 23% of the analyzed publications contained quantitative data on DDSs subcellular targeting efficiency, while the majority of publications reported qualitative results only. From the analysis of publications in the subcellular targeting field, it appears that insufficient efforts are devoted to quantitative analysis of the major formulation parameters and of the DDSs’ intracellular fate. Based on these findings, we provide recommendations for future studies in the field of organelle-specific drug delivery and targeting.

Apoptotic efficacy of biogenic silver nanoparticles on human breast cancer MCF-7 cell lines.

This article describes the synthesis of silver nanoparticles using the aqueous extract of Alternanthera sessilis as a reducing agent by sonication, espousing green chemistry principles. Biologically synthesized nanoparticle-based drug delivery systems have significant potential in the field of biopharmaceutics due to its smaller size entailing high surface area and synergistic effects of embedded biomolecules. In the present work the cytotoxic effect of biosynthesized silver nanoparticles studied by MTT assay against breast cancer cells (MCF-7 cell line) showed significant cytotoxic activity with IC50 value 3.04 μg/mL compared to that of standard cisplatin. The superior activity of the silver nanoparticles may be due to the spherical shape and smaller particle size 10–30 nm as confirmed from transmission electron microscope (TEM) analysis. The data obtained in the study reveal the potent therapeutic value of biogenic silver nanoparticles and the scope for further development of anticancer drugs.

Comparison of the uptake of methacrylate-based nanoparticles in static and dynamic in vitro systems as well as in vivo

Polymer-based nanoparticles are promising drug delivery systems allowing the development of new drug and treatment strategies with reduced side effects. However, it remains a challenge to screen for new and effective nanoparticle-based systems in vitro. Important factors influencing the behavior of nanoparticles in vivo cannot be simulated in screening assays in vitro, which still represent the main tools in academic research and pharmaceutical industry. These systems have serious drawbacks in the development of nanoparticle-based drug delivery systems, since they do not consider the highly complex processes influencing nanoparticle clearance, distribution, and uptake in vivo. In particular, the transfer of in vitro nanoparticle performance to in vivo models often fails, demonstrating the urgent need for novel in vitro tools that can imitate aspects of the in vivo situation more accurate. Dynamic cell culture, where cells are cultured and incubated in the presence of shear stress has the potential to bridge this gap by mimicking key-features of organs and vessels. Our approach implements and compares a chip-based dynamic cell culture model to the common static cell culture and mouse model to assess its capability to predict the in vivo success more accurately, by using a well-defined poly((methyl methacrylate)-co-(methacrylic acid)) and poly((methyl methacrylate)-co-(2-dimethylamino ethylmethacrylate)) based nanoparticle library. After characterization in static and dynamic in vitro cell culture we were able to show that physiological conditions such as cell–cell communication of co-cultured endothelial cells and macrophages as well as mechanotransductive signaling through shear stress significantly alter cellular nanoparticle uptake. In addition, it could be demonstrated by using dynamic cell cultures that the in vivo situation is simulated more accurately and thereby can be applied as a novel system to investigate the performance of nanoparticle systems in vivo more reliable.

Abstract LB-102: Layer-by-layer engineering of upconversion nanoparticle based siRNA and miRNA delivery system for cancer therapy

Abstract Purpose: Nanoparticle based drug delivery systems have shown promising applications in cancer treatments. Among various nanoparticles, upconversion nanoparticles (UCNPs) allow for the conversion of near infrared (NIR) excitation to localized UV/visible emission providing unprecedented control over UCNP based delivery platforms for deep tissue therapeutic payload release, both spatially and temporally. This study reports the layer-by-layer engineering of UCNP based siRNA and miRNA delivery systems for application in cancer therapy. Experimental Design: To obtain the nanoparticle core, NaYF4:Yb,Er UCNPs were synthesized via thermal decomposition method. The morphology and size of the UCNPs were assessed by transmission electron microscopic (TEM). The upconversion fluorescence property was studied by fluorescence spectroscopy using a 980 nm laser as the excitation source. To enable gene delivery, the naked UCNPs were then surface functionalized with biocompatible polymers using polyacrylic acid (PAA) and poly allylamine hydrochloride (PAH). Surface functionalization was accomplished through layer-by-layer assembly of polyelectrolyte multilayers. Successful surface functionalization was demonstrated by measuring zeta potential after assembly of each layer. Biocompatibility of the developed delivery system was tested by MTT assay. Gel electrophoresis was employed to determine the loading capacity of the delivery system. We then tested the siRNA, miRNA, and EGFP expression vector transfection efficiency in different cancer cell lines. Results: The diameter of the synthesized UCNPs was ∼40 nm. Upon 980 nm excitation, green emission and red emission were identified from the fluorescence spectrum. Zeta potential of the delivery system was ∼+38 mV, indicating its capability to absorb negatively charged siRNA, miRNA, or EGFP vector by electrostatic interaction. The MTT assay demonstrated good biocompatibility. Significant retardation of siRNA, miRNA, or EGFP plasmid in gel electrophoresis assay was observed when mixed with PAA and PAH coated UCNPs. In contrast, UCNP-PAA without PAH coating did not retard siRNA, miRNA, or EGFP plasmid. Confocal laser scanning microscopy results provided direct evidence of siRNA, miRNA, or EGFP plasmid transfection. Conclusions: In this proof-of-concept study, a layer-by-layer engineered UCNP based siRNA and miRNA delivery system was successfully developed. Our novel delivery system opens up preparation of advanced UCNP based photoresponsive delivery systems that allow remote, precise, and trackable control over therapeutic payload (e.g., drug, gene) release for better cancer theranostics. Citation Format: Lin Min, YAN GAO, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan. Layer-by-layer engineering of upconversion nanoparticle based siRNA and miRNA delivery system for cancer therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-102. doi:10.1158/1538-7445.AM2015-LB-102

Abstract A119: Assessment and optimization of electroporation assisted tumoral nanoparticle uptake in a pancreatic adenocarcinoma nude mouse model

Abstract Summary: Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal form of cancer. In 2012, the incidence of PDAC was 43,920. Five year survival for patients with PDAC was 6%, regardless of staging, making PDAC one of the deadliest forms of cancer. One reason for such dismal prognosis is chemoresistance to the current first-line therapy of choice, gemcitabine. There are multiple factors which contribute to chemoresistance observed in pancreatic cancer. Among them, desmoplasia has been increasingly seen as a significant contributor to chemoresistance in PDAC. To overcome desmoplastic chemoresistance, several novel methods of treatment have been developed. Electroporation is one such novel treatment. High electrical fields are applied to cells to create pores which increase the cell permeability. It has been previously demonstrated that electroporation enhances therapeutic efficacy of anticancer drugs in pancreatic tumor models. Nanoparticle-based drug delivery systems constitute a second novel method to overcome desmoplastic chemoresistance. Due to their intrinsic design advantages, nanoparticles have been shown to increase effectiveness of chemotherapeutic agents, while further reducing or even eliminating side effects. To date, there have been no studies to evaluate the cumulative effect of combining both nanoparticle and electroporation strategies to overcome chemoresistance in PDAC. Objective: Our laboratory conducted preliminary studies using a panc-1 athymic nude mouse model to assess doxorubicin iron oxide nanoparticle uptake as a function of electroporation voltage and timing. Our studies showed that electroporation with iron oxide doxorubicin nanoparticle administration increases nanoparticle uptake in panc-1 cell line athymic nude mouse models of PDAC. Methods: Our experiment first assessed the in vitro uptake of doxorubicin-iron oxide nanoparticles and cell viability in panc-1 cells, to optimized electroporation voltage setting to maximize iron uptake without excessive cell death. 2 million panc-1 cells were placed in 1 ml of DMEM with or without 100 nM of iron oxide doxorubicin nanoparticles. Each plate of cells were individually electroporated at voltages from 0 to 1500. The cells were then incubated for another 24 hours. Cells were trypsonized and evaluated for cell viability and iron uptake by flow cytometry and inductively coupled plasma mass spectrometry, respectively. For our in vivo study, mouse xenograft models were inoculated with 5x106 panc-1 human PDAC cell line into the left and right flank tissues to grow tumors roughly 10 mm in size. Once the tumors reached 10mm, the mice were anesthetized. The mice were then randomized into electroporation-nanoparticle administration timing study limbs ranging from electroporation 12 minutes before nanoparticle administration to electroporation 12 minutes after nanoparticle administration. One hour after the administration of nanoparticles, the mice were euthanized and the tumors were excised. Iron content for each tumor sample was analyzed quantitatively and qualitatively, using ICP-MS and H&E staining with Prussian Blue. Results: From our in vitro study, we found that voltage setting of 400V optimally allowed reversible electroporation without excessive cell death. Our in vivo study demonstrated that electroporation 3 minutes after administration of intravenous nanoparticles provided the greatest degree of intratumoral particle uptake. Conclusions: Significant improvement in chemotherapeutic uptake can be achieved, using optimized nanoparticle and electroporation settings to overcome the intrinsic chemoresistance in PDAC. Citation Format: Derek Lamont West, Sarah White, Zhuoli Zhang, Andrew Larson, Reed Omary. Assessment and optimization of electroporation assisted tumoral nanoparticle uptake in a pancreatic adenocarcinoma nude mouse model. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A119.

Polyphenols and Bionanoparticle Combinations as Neuroprotective and Anticarcinogenic Agents: A Potential Neuropharmacological Solution to Combat Cerebral Stroke and Cancer

Polyphenols are naturally occurring organic materials that can be leveraged to develop extremely efficient drug agents for prevention in cerebral stroke related injuries and for chemotherapeutic purposes. Ongoing research on clinically important polyphenolic materials such as resveratrol and flavanols has indicated an immense potential for new drug design for treatment and prevention of cerebral ischemic stroke and other novel chemotherapeutic applications. In this short review, we have highlighted recent developments in this area to facilitate further research on this important class of organic materials for new biomedical applications that include nanoparticles based drug delivery systems.

Regulation of BAX/BCL2 gene expression in breast cancer cells by docetaxel-loaded human serum albumin nanoparticles.

Today, using nanoparticle-based drug delivery systems has expanded to avoid anticancer side effects. Taxanes are important chemotherapeutic agents in the treatment of metastatic breast cancer. In this study, docetaxel (DTX)-loaded human serum albumin (HSA) nanoparticles (NPs) were prepared and characterized. Drug toxicity of the nanoparticles was measured by MTT assay with different drug concentrations (0.01, 0.1, 0.5, 1 and 5 μM) at different incubation times (24, 48 and 72 h). Expression of BAX/BCL2 mRNA levels was determined by real-time PCR. The size of NPs prepared and used in our study was about 147 nm with surface charge of -29.6 mV. Results obtained from MTT assay showed that 0.5 μM of free drug had 50 % toxicity on MCF-7 cells after 48-h incubation. Real-time PCR results showed an increase in expression of BAX and no change for BCL2. In conclusion, a significant overexpression of BAX gene and changes in BAX/BCL2 ratio were observed for DTX-loaded HSA nanoparticles compared with free DTX and may provide a potential therapy to inhibit anticancer drug resistance.

Nanotechnology in respiratory medicine.

Like two sides of the same coin, nanotechnology can be both boon and bane for respiratory medicine. Nanomaterials open new ways in diagnostics and treatment of lung diseases. Nanoparticle based drug delivery systems can help against diseases such as lung cancer, tuberculosis, and pulmonary fibrosis. Moreover, nanoparticles can be loaded with DNA and act as vectors for gene therapy in diseases like cystic fibrosis. Even lung diagnostics with computer tomography (CT) or magnetic resonance imaging (MRI) profits from new nanoparticle based contrast agents. However, the risks of nanotechnology also have to be taken into consideration as engineered nanomaterials resemble natural fine dusts and fibers, which are known to be harmful for the respiratory system in many cases. Recent studies have shown that nanoparticles in the respiratory tract can influence the immune system, can create oxidative stress and even cause genotoxicity. Another important aspect to assess the safety of nanotechnology based products is the absorption of nanoparticles. It was demonstrated that the amount of pulmonary nanoparticle uptake not only depends on physical and chemical nanoparticle characteristics but also on the health status of the organism. The huge diversity in nanotechnology could revolutionize medicine but makes safety assessment a challenging task.

Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics.

In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future.

Core-Cross-Linking Accelerates Antitumor Activities of Paclitaxel-Conjugate Micelles to Prostate Multicellular Tumor Spheroids: A Comparison of 2D and 3D Models.

The 2D monolayer cell culture model is often the first step in the prediction of the success or failure of a nanoparticle-based drug delivery system. However, there is often poor translation between the 2D monolayer in vitro results and the nanoparticle-drug performance in vivo. One possible way of bridging this gap is the use of multicellular tumor spheroids (MCTSs) as an intermediate in vitro model due to its 3D structure. This paper aims to quantify and compare the results obtained from traditional 2D monolayer cell cultures and 3D MCTS by studying the cytotoxic effects of free paclitaxel (PTX) and paclitaxel, which has been conjugated to a poly(ethylene glycol methyl ether acrylate)-b-poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer and self-assembled to give a micellar delivery system. The core of the micelle was cross-linked with a diamino nondegradable cross-linker to compare the effects of micelle stability on the results. Although the 2D prostate tumor cell culture results indicated that all micellar variants (IC50: 193-271 nM) were significantly less toxic than free paclitaxel (IC50: 15.2 nM), the micelles showed faster and higher cytotoxicity than free PTX in the 3D prostate MCTS. The cross-linking of micelles even showed accelerated antitumor activities to the MCTS compared with un-cross-linked micelles. The results indicate that DAO-cross-linked POEGMEA-b-PCEA-PTX conjugate micelles will be a useful nanodrug carrier for prostate cancer therapy. MCTS offers a very promising method of incorporating 3D structures into in vitro testing.

Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.

Next-generation nanoparticle-based drug delivery systems require the ability to target specific organelles or subcellular regions in selected target cells. Human immunodeficiency virus type I (HIV-1) particles are evolutionarily optimized nanocarriers that have evolved to avoid intracellular degradation and achieve enrichment at the synapse between mature dendritic cells (mDCs) and T cells by subverting cellular trafficking mechanisms. This study demonstrates that integration of the glycosphingolipid, GM3, in a membrane around a solid nanoparticle (NP) core is sufficient to recapitulate key aspects of the virus particle trafficking in mDCs. GM3-presenting artificial virus NPs (GM3-AVNs) accumulate in CD169(+) and CD81(+) nonlysosomal compartments in an actin-dependent process that mimics the sequestration of HIV-1. Live-cell optical tracking studies reveal a preferential recruitment and arrest of surface scanning CD4(+) T cells in direct vicinity to the AVN-enriched compartments. The formed mDC-T cell conjugates exhibit strong morphological similarities between the GM3-AVN-containing mDC-T cell synapse and the HIV-1 virological synapse, indicating that GM3-CD169 interactions alone are sufficient for establishing the mDC-T cell virological synapse. These results emphasize the potential of the GM3-AVN approach for providing therapeutic access to a key step of the host immune response--formation of the synaptic junction between an antigen-presenting cell (mDC) and T cells--for modulating and controlling immune responses.

An Iron Oxide Nanocarrier Loaded with a Pt(IV) Prodrug and Immunostimulatory dsRNA for Combining Complementary Cancer Killing Effects.

There is major current interest in harnessing the immune system against cancer and in developing drugs that provide complementary cancer killing mechanisms. Although the recent advent of nanoparticle-based drug delivery systems has improved the efficacy of platinum drugs for chemotherapy, one of the fundamental paradigms in their design and use is evading surveillance by the immune system to enhance anticancer efficacy. However, new studies are showing that chemotherapy can profit from actively targeting stimulation of the immune system and that suitably functionalized nanomaterials might be ideal for overcoming some key challenges in immunotherapy. Pt(IV) prodrug-modified PEGylated phospholipid micelles that encapsulate biocompatible iron oxide nanoparticles (IONPs) as a new delivery system for cisplatin are reported. The Pt(IV)-IONPs are functionalized with polyinosinic-polycytidylic acid (poly (I:C))--a double stranded RNA (dsRNA) analog widely used as an adjuvant in clinical trials of cancer immunotherapy. The Pt(IV)-IONPs and poly (I:C)--Pt(IV)-IONPs enhance by more than an order of magnitude the prodrug cytotoxicity in different tumor cells, while greatly increasing the ability of cisplatin and poly (I:C) to activate dendritic cells--the key cellular players in immunotherapy. The results suggest that these constructs hold promise for targeted chemoimmunotherapy.

Recent advances in utilization of photochemical internalization (PCI) for efficient nano carrier mediated drug delivery

Despite recent progresses in nanoparticle-based drug delivery systems, there are still many unsolved limitations. Most of all, a major obstacle in current nanoparticle-based drug carrier is the lack of sufficient drug delivery into target cells due to various biological barriers, such as: extracellular matrix, endolysosomal barrier, and drug-resistance associated proteins. To circumvent these limitations, several research groups have utilized photochemical internalization (PCI), an extension of photodynamic therapy (PDT), in design of innovative and efficient nano-carriers drug delivery. This review presents an overview of a recent research on utilization of PCI in various fields including: anti-cancer therapy, protein delivery, and tissue engineering.

Neuropeptide Y Y1 receptors mediate [corrected] targeted delivery of anticancer drug with encapsulated nanoparticles to breast cancer cells with high selectivity and its potential for breast cancer therapy.

By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

S-layer fusion protein as a tool functionalizing emulsomes and CurcuEmulsomes for antibody binding and targeting

Selective targeting of tumor cells by nanoparticle-based drug delivery systems is highly desirable because it maximizes the drug concentration at the desired target while simultaneously protecting the surrounding healthy tissues. Here, we show a design for smart nanocarriers based on a biomimetic approach that utilizes the building principle of virus envelope structures. Emulsomes and CurcuEmulsomes comprising a tripalmitin solid core surrounded by phospholipid layers are modified by S-layer proteins that self-assemble into a two-dimensional array to form a surface layer. One significant advantage of this nanoformulation is that it increases the solubility of the lipophilic anti-cancer agent curcumin in the CurcuEmulsomes by a factor of 2700. In order to make the emulsomes specific for IgG, the S-layer protein is fused with two protein G domains. This S-layer fusion protein preserves its recrystallization characteristics, forming an ordered surface layer (square lattice with 13nm unit-by-unit distance). The GG domains are presented in a predicted orientation and exhibit a selective binding affinity for IgG.

CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer.

EPR-Effect and Nano-medicine Backdoor or Bottleneck?

Cancers are a leading cause of death today as they will be in the future. Chemotherapy is one of the major weapons we have in the ill equipped battle against this important human threat. Despite several drawbacks, nanoparticle based drug delivery systems (DDS) hold promise to ameliorate anticancer chemotherapy. From the beginning of “Nano medicine” by the discovery of liposomes by Bangham et al. in 1965

Formulation and Characterization of Pyrazinamide Polymeric Nanoparticles for Pulmonary Tuberculosis: Efficiency for Alveolar Macrophage Targeting.

Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared dispersions were characterized for various biopharmaceutical parameters such as particle size, zeta potential, polydispersity index, drug loading capacity, entrapment efficiency and targeting to alveolar macrophages. The formulated polymeric nanoparticles were in the particle size range of 45.51 to 300.4 nm with a maximum drug entrapment efficiency of 80.9%. The stability study of optimized batch conducted at 40±2°/75±5% relative humidity showed no significant changes up to 90 days. X-Ray Diffraction spectrum exhibits the transformation of crystalline form of drug to amorphous in the formulation. Scanning Electron Microscope image showed nanoparticles spherical in shape with smooth surface. In vitro release profiles were biphasic in nature with burst release followed by controlled release over a period of 24 h obeying diffusion mechanism. In vivo and ex vivo studies results of the study show significant uptake of the nanoparticles by alveolar macrophages through fluorescent micrograph. Polymeric nanoparticles formulation of pyrazinamide could encompass significant uptake by alveolar macrophages, the high first-pass metabolism, sustain the release of drug leading to reduction in dose, toxicity and improvement of patient compliance.

Copper Prussian blue analogue: investigation into multifunctional activities for biomedical applications.

We have designed and developed stable and biocompatible copper analogues of a Prussian blue (PB) nanoparticle based drug delivery system containing doxorubicin that show selective quenching of fluorescence of doxorubicin compared to PB analogues with other metals and inhibition of cancer cell proliferation, suggesting future potential multifunctional applications in biomedical sciences.