Lipid nanocarrier targeting activated macrophages for antiretroviral therapy of HIV reservoir.

To develop lipid nano-antiretrovirals (LNAs) for the treatment of HIV-infected macrophages. LNAs were prepared with docosahexaenoic acid to facilitate brain penetration and surface-decorated with folate considering that infected macrophages often overexpress folate receptors. Folate-decorated LNAs loading rilpivirine (RPV) were efficiently taken up by folate receptor-expressing cell types including activated macrophages.

Polypharmacy and cumulative anticholinergic burden in older adults hospitalized with fall.

Introduction: Polypharmacy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalized with falls.

Methods: A noninterventional, prospective cohort study of unselected, acute admissions aged ≥ 65 years.

Development of local injectable, bone-targeting nanocarriers of triptolide for treatment of bone-only metastasis.

Triptolide (TP) is known for its diverse pharmacological activities but also its delivery and toxicity issues. This study aimed at exploiting TP's anticancer effects at lower risk of systemic toxicity by developing local-injectable "bone-targeting TP nanoparticle" (TPN) for bone-only metastasis treatment. The lipid/oil-based TPNs decorated with alendronate (ALE) achieved size of 70.

Development of a high payload, cancer-targeting liposomes of methyl aminolevulinate for intraoperative photodynamic diagnosis/therapy of peritoneal carcinomatosis.

Methyl aminolevulinate (MAL) is a photosensitizer topically used for photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of skin pre-cancers and cancers. In this study, our goal is to expand the application of MAL to dual intraoperative PDD and PDT of peritoneal carcinomatosis. A new liposomal MAL formulation (lipMAL) designed for systemic or intraperitoneal administration was developed.

Incorporation of docosahexaenoic acid (DHA) enhances nanodelivery of antiretroviral across the blood-brain barrier for treatment of HIV reservoir in brain.

Although the newer antiretroviral (ARV) drugs are highly active against the human immunodeficiency virus (HIV) in the body compartment, they often fail to effectively tackle the HIV reservoir in the brain because of inefficient penetration to the blood-brain barrier (BBB). In this study, we investigated the potential benefits of incorporating docosahexaenoic acid (DHA), an omega-3 fatty acid essential for brain development, in lipid nanocarriers for facilitating the BBB passage of an ARV darunavir. The resulting nanocarriers (nanoARVs) containing 5-15% DHA were 90-140 nm in size, had high darunavir payload (~11-13% w/w), good stability and minimal cellular toxicity, and could be further decorated with transferrin (Tf) for Tf-receptor targeting.

Enhanced eradication of intracellular and biofilm-residing methicillin-resistant Staphylococcus aureus (MRSA) reservoirs with hybrid nanoparticles delivering rifampicin.

Osteomyelitis carries a high risk of recurrence even after extended, aggressive antibiotic therapy. One of the key challenges is to eradicate the reservoirs of methicillin-resistant Staphylococcus aureus (MRSA) inside the host bone cells and their biofilms. Our goal is to develop rifampicin loaded lipid-polymer hybrid nanocarriers (Rf-LPN) and evaluate if they can achieve enhanced rifampicin delivery to eradicate these intracellular and biofilm-residing MRSA.

Lipid-polymer hybrid nanoparticles carrying linezolid improve treatment of methicillin-resistant Staphylococcus aureus (MRSA) harbored inside bone cells and biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent pathogen causing osteomyelitis. The tendency of MRSA to evade standard antibiotic treatment by hiding inside bone cells and biofilms is a major cause of frequent osteomyelitis recurrence. In this study, we developed a lipid-polymer hybrid nanoparticle loading the antibiotic linezolid (LIN-LPN), and focused on evaluating if this new nanoantibiotic can achieve significant in vitro activities against these intracellular and biofilm-embedded MRSA.

Therapeutic Nanotechnology for Bone Infection Treatment - State of the Art.

Despite extended, aggressive use of conventional antibiotics, drug treatment of bone infections frequently fails as a combined result of the widespread of drug-resistant bacteria, poor accessibility of many antimicrobials to the deeper portion of the bones, the ease of biofilm formation on the bone surface, and high risk of drug toxicity. Emerging therapeutic nanotechnology offers potential solutions to these issues. In recent years, a number of nanoantimicrobials, i.

Nanomedicine applications in the treatment of breast cancer: current state of the art.

Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil and Abraxane have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes.

Enhanced neuroprotection with decellularized brain extracellular matrix containing bFGF after intracerebral transplantation in Parkinson's disease rat model.

Extracellular matrix-based biomaterials have many advantages over synthetic polymer materials for regenerative medicine applications. In central nervous system (CNS), basic fibroblast growth factor (bFGF) is widely studied as a potential agent for Parkinson's disease (PD). However, the poor stability of bFGF hampered its clinical use.

A biodistribution study of solid lipid-polyethyleneimine hybrid nanocarrier for cancer RNAi therapy.

Solid lipid-polymer hybrid nanocarrier (LPN) was previously reported to achieve high siRNA transfection efficiency and induce sustained RNAi-based chemosensitizing effect at cellular level. In this study, our objectives were to evaluate the in vivo biodistribution of LPNs in a prostate cancer model and determine the factors that potentially affect tumor penetration by LPNs. The LPN formulation with the highest transfection efficiency (64%) and stability was selected for the study.

Development and evaluation of viscosity-enhanced nanocarrier (VEN) for oral insulin delivery.

Solid lipid nanoparticles (SLN) have demonstrated good potential for oral peptide delivery. However, their hydrophobic nature generally accounts for low peptide entrapment efficiency (EE%). In this study, a new strategy was adopted to improve peptide EE% by incorporating a hydrophilic viscosity-enhancing agent (VA) within SLN cores to develop viscosity enhanced nanocarriers (VEN).

Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.

Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy.

Methocel-Lipid Hybrid Nanocarrier for Efficient Oral Insulin Delivery.

Even with the use of double-emulsion technique for preparation, the hydrophobic nature of solid lipid nanoparticles (SLNs) limits their encapsulation efficiency (EE%) for peptides such as insulin. In this study, we hypothesize that inclusion of Methocel into SLN to form Methocel-lipid hybrid nanocarriers (MLNs) will significantly enhance insulin EE% without compromising the various characteristics of SLN favorable for oral drug delivery. Our data show that incorporation of 2% wt/wt of Methocel A15C had doubled insulin EE% (around 40%) versus conventional SLN prepared using standard double emulsion technique.

Glioma-targeted therapy using Cilengitide nanoparticles combined with UTMD enhanced delivery.

Malignant gliomas especially glioblastoma (GBM) are poorly responsive to the current treatments. Cilengitide (CGT) is a cyclic pentapeptide that demonstrated efficacy for GBM treatment by targeting the integrins avβ3 and avβ5 over-expressed on GBM cells. However, clinical translation of this therapy has been limited by issues including fast blood clearance, high kidney and liver uptake, poor blood-brain barrier (BBB) penetration, low tumor specificity and rapid washout from tumors.

Intranasal delivery of bFGF with nanoliposomes enhances in vivo neuroprotection and neural injury recovery in a rodent stroke model.

Basic fibroblast growth factor (bFGF) may protect stroke patients from cerebral ischemia-reperfusion (I/R) injury. In this study, we report the intranasal use of novel nanoliposomes for the brain delivery of bFGF in a rat model of cerebral I/R. Compared with free bFGF, nanoliposomal therapy was able to significantly improve bFGF accumulation in brain tissues (p<0.

Prevent diabetic cardiomyopathy in diabetic rats by combined therapy of aFGF-loaded nanoparticles and ultrasound-targeted microbubble destruction technique.

Acidic fibroblast growth factor (aFGF) has shown the great potential to prevent the structural and functional injuries caused by diabetic cardiomyopathy (DCM). The present study sought to investigate the preclinical performance and mechanism of the combination therapy of aFGF-nanoparticles (aFGF-NP) and ultrasound-targeted microbubble destruction (UTMD) technique for DCM prevention. From Mason staining and TUNEL staining, aFGF-NP+UTMD group showed significant differences from the diabetes group and other groups treated with aFGF or aFGF-NP.

Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury.

Objective: Nerve growth factor (NGF) has potential in spinal cord injury (SCI) therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Novel heparin-poloxamer (HP) thermo-sensitive hydrogel was constructed to enhance the NGF regeneration on SCI.

Method: NGF-HP thermo-sensitive hydrogel was prepared and related characteristics including gelation temperature, rheological behavior and micromorphology were measured.

Lipid-Based Nanocarriers for RNA Delivery.

RNA-interference (RNAi) agents such as small-interfering RNA (siRNA) and micro-RNA (miRNA) have strong potential as therapeutic agents for the treatment of a broad range of diseases such as malignancies, infections, autoimmune diseases and neurological diseases that are associated with undesirable gene expression. In recent years, several clinical trials of RNAi therapeutics especially siRNAs have been conducted with limited success so far. For systemic administration of these poorly permeable and easily degradable macromolecules, it is obvious that a safe and efficient delivery platform is highly desirable.

Current approaches to enhance CNS delivery of drugs across the brain barriers.

Although many agents have therapeutic potentials for central nervous system (CNS) diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood-brain barrier and the blood-cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied.

A new nanostructured carrier design including oil to enhance the pharmaceutical properties of retinoid therapy and its therapeutic effects on chemo-resistant ovarian cancer.

All-trans retinoic acid (ATRA) is an appealing alternative drug for the cancers that have failed the conventional chemotherapy and become chemo-resistant and more tumorigenic. In this study, we specifically addressed two issues commonly associated with ATRA nanotherapeutics: (1) insufficient, unstable entrapment and uncontrolled release of the highly lipophilic ATRA and (2) lack of studies in therapeutically relevant chemo-resistant cancer cell models. A polymer-oil nanostructured carrier (PONC) composed of oil and PLGA was designed and studied in an ovarian cancer cell subline SKOV-3PR that could withstand up to 300 nM paclitaxel and expressed high levels of multidrug resistance transporter ABCB1 and tumorigenic marker CD133.

Functional and pathological improvements of the hearts in diabetes model by the combined therapy of bFGF-loaded nanoparticles with ultrasound-targeted microbubble destruction.

Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats.

Nanocarrier for poorly water-soluble anticancer drugs--barriers of translation and solutions.

Many existing chemotherapeutic drugs, repurposed drugs and newly developed small-molecule anticancer compounds have high lipophilicity and low water-solubility. Currently, these poorly water-soluble anticancer drugs (PWSAD) are generally solubilized using high concentrations of surfactants and co-solvents, which frequently lead to adverse side effects. In recent years, researchers have been actively exploring the use of nanotechnology as an alternative to the solvent-based drug solubilization approach.