Penetration of PLGA nanoparticles into the intracranial rat C6 Glioma: Influence of surfactant coating

As shown by our previous studies, the PLGA nanoparticles (NP) coated with poloxamer 188 (P188) enable brain delivery of doxorubicin and its high anti-tumour effect against the intracranial glioblastoma in rats [1]. The objective of the present study was to evaluate the uptake of the P188-coated PLGA NP in the intracranial C6 glioma in rats. For visualization using scanning laser confocal microscopy (SLCM) and an intravital fluorescence imaging system IvisÒSpectrum CT (Perkin-Elmer), the NP were labeled with DiI (DiI-PLGA NP). The DiI-PLGA NP were administered i.v. into rats with intracranial C6 glioma on day 15 after tumour implantation. The presence of mass lesion was verified by previous MRI. Two hours after administration of the NP, the rats were perfused transcardially with paraformaldehyde, organs were recovered, and the fluorescence intensity was assessed using an IvisÒSpectrum CT system. The fluorescence intensity of the hemisphere with the implanted glioma was \u3e 4-fold higher for the P188-coated NP (DiI-PLGA/P188 NP), as compared to the uncoated NP (45.1×106 vs 9.5×106 photons/sec/cm2, respectively (Figure). The quantitative fluorescence analysis on the tumor sections using SLCM also showed a significantly higher accumulation of the DiI-PLGA/P188 NP, as compared to the uncoated DiI-PLGA NP (Fig. 2). Mean fluorescence intensity values in the tumor were 1698.9±536.6 and 558.9±181.0 CU for the P188-coated and uncoated NP, respectively. The intensity values in the contralateral hemispheres for the same preparations were 293.4 ± 32.3 and 203.2 ± 22.9 CU, respectively. Thus, according to the SLCM data, the penetration of the DiI-PLGA/P188 NP into the tumor was 3 times more effective than that of the uncoated NP. Please click Additional Files below to see the full abstract

The Potential Advantages of Nanoparticle Drug Delivery Systems in Chemotherapy of Tuberculosis

Nanoparticle-based drug delivery systems have considerable potential for treatment of tuberculosis (TB). The important technological advantages of nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation. Nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix. These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency, and may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics. This article highlights some of the issues of nanotechnology relevant to the anti-TB drugs

Pharmaceutical Development of Nanostructured Vesicular Hydrogel Formulations of Rifampicin for Wound Healing

Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifampicin is sensitive to hydrolysis and oxidation. As a result, no topical drug product for wound-healing applications has been approved. To address this medical need two nanostructured hydrogel formulations of rifampicin were developed. The liposomal vesicles were embedded into hydroxypropyl methylcellulose (HPMC) gel or a combination of hyaluronic acid and marine collagen. To protect rifampicin from degradation in aqueous environments, a freeze-drying method was developed. Before freeze-drying, two well-defined hydrogel preparations were obtained. After freeze-drying, the visual appearance, chemical stability, residual moisture content, and redispersion time of both preparations were within acceptable limits. However, the morphological characterization revealed an increase in the vesicle size for collagen–hyaluronic acid hydrogel. This was confirmed by subsequent release studies. Interactions of marine collagen with phosphatidylcholine were held responsible for this effect. The HPMC hydrogel formulation remained stable over 6 months of storage. Moving forward, this product fulfills all criteria to be evaluated in preclinical and clinical studies

Release of doxorubicin from different types of PLGA nanoparticles stabilized by human serum albumin (water, 37°C, n = 3).

<p>Release of doxorubicin from different types of PLGA nanoparticles stabilized by human serum albumin (water, 37°C, n = 3).</p

The blood-brain barrier and beyond: Nano-based neuropharmacology and the role of extracellular matrix

Restrained drug delivery due to the blood-brain barrier (BBB) considerably limits options for the treatment of brain pathologies. The utilization of nanoparticulate (NP) carriers has been proposed as a solution. The development strategies need to address the important hurdle of NP passage across the BBB as well as the altered cellular up-take due to the pathophysiological changes of the damaged or diseased tissue as well as immunological and toxicological aspects of nanomedicine penetration. This review therefore scopes to: 1) outline the state-of-the art knowledge on BBB passage, 2) address the significant influence of pathological conditions on nanoparticulate drug delivery, and, 3) highlight the largely neglected role of the extracellular matrix (ECM). Interactions of the nanosystem with biological barriers, cells and ECM in the milieu of brain pathologies are critically discussed in order to present a holistic overview of the advances and pits of nanomedicine applications in brain disease

Semi-quantitative analysis of the extent of necrosis after treatment with Dox-PLGA formulations, Dox-sol, and surfactant solution.

<p>Semi-quantitative analysis of the extent of necrosis after treatment with Dox-PLGA formulations, Dox-sol, and surfactant solution.</p

Physicochemical parameters of the doxorubicin-loaded PLGA-nanoparticles.

<p>Physicochemical parameters of the doxorubicin-loaded PLGA-nanoparticles.</p

Quantitative analysis of tumour incidence, tumour size, proliferation index, and vessel density as well as semiquantitative analysis of GFAP- and VEGF expression after chemotherapy of 101/8 rat glioblastoma with different formulations of doxorubicin.

<p>Quantitative analysis of tumour incidence, tumour size, proliferation index, and vessel density as well as semiquantitative analysis of GFAP- and VEGF expression after chemotherapy of 101/8 rat glioblastoma with different formulations of doxorubicin.</p