Despite benefits of systemic chemotherapy in breast cancer treatment, several patients with early-stage breast cancer will develop metastatic breast cancer (MBC). Doxorubicin is among the most active agents against MBC. However, the use of doxorubicin is related to some life-threatening side effects including cardiotoxicity. Many efforts were made to lessen the side effects of doxorubicin and improve its efficacy. Pegylated liposomal doxorubicin (PLD) is a product claimed to achieve these two objectives because of its different pharmacokinetic profile. The aim of this study was to determine the side-effect profile of PLD in MBC through a systematic review of phase II clinical trials. A literature search in PubMed-MEDLINE was performed using terms covering nano-based pharmaceutical systems, 'breast cancer' and 'doxorubicin'. Articles were evaluated according to the inclusion criteria. Reported hematological and non-hematological side effects were categorized. Out of 718 articles that were initially identified, 8 were in accordance with the inclusion criteria. We found that the most important side effects of PLD were skin toxicity and mucositis, but the proportion of patients who showed grade III and IV of these side effects was relatively low. On the other hand, the occurrence of cardiotoxicity, the most important problem with doxorubicin, was considerably reduced in patients treated with PLD. Although PLD has demonstrated a lower toxicity profile than conventional anthracyclines, it has also new side effects. However, it seems that the reduced cardiotoxicity of PLD has made it a more appropriate option in patients with MBC, especially in those with risk factors for cardiac diseases.

Delivery to the lungs is an efficient way to deliver drugs directly to the site of action or to the blood circulation. Because of limitations of direct administration of free drugs, particulate drug delivery systems such as DPI formulations based on nanoparticles (NPs) have been of interest for pulmonary drug delivery. The prolonged residence of NPs in the lungs due to ability to escape from the clearance mechanisms such as mucociliary escalator, macrophage uptake (a size of 1-2 µm is ideal for macrophage phagocytosis), and translocation to the systemic circulation is amongst the key advantages of NPs. By this approach, the controlled pulmonary delivery of drugs, peptides, proteins, genes, siRNA, and vaccines is possible. Both natural (albumin, gelatin, alginate, collagen, cyclodextrin, and chitosan) and synthetic (poly (lactide-co-glycolide) (PLGA), polyacrylates and polyanhydrides) polymers have been used in formulation of pulmonary nanovectors. As direct pulmonary administration of NPs is not feasible, by using the safe excipients, NPs could be converted to dry powder inhaler (DPI) formulations. These can provide a promising deposition and stability of NPs. In this article, the DPI formulations based on polymeric nanoparticles have been reviewed and categorized based on the polymer type used for preparation of NPs.

Regenerative endodontics is the creation and delivery of tissues to replace diseased, missing, and traumatized pulp. A call for a paradigm shift and new protocol for the clinical management of these cases has been brought to attention. These regenerative endodontic techniques will possibly involve some combination of disinfection or debridement of infected root canal systems with apical enlargement to permit revascularization and use of stem cells, scaffolds, and growth factors. Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells (DPSCs)) and deciduous teeth (stem cells from human exfoliated deciduous teeth). Stem cells are characterized as multipotent cells for regeneration.These three case reports describe the treatment of necrotic or immature teeth with periradicular periodontitis, which was not treated with conventional apexification techniques. All cases presented here developed mature apices and bone healing after 3 to 4 months after the initial treatment without complications, and faster than traditional treatments. Our clinical observations support a shifting paradigm toward a biologic approach by providing a favorable environment for tissue regeneration. The mechanism of this continued development and formation of the root end and faster tissue healing is discussed.

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Purpose: Direct delivery of aminoglycosides to the lungs was under extensive evaluations during the last decades. Because of large particle size, low density and porous structure, large porous particles (LPPs) are versatile carriers for this purpose. In this study, poly (lactic-co-glycolic acid) (PLGA) LPPs encapsulating gentamicin sulfate were prepared and in vitro characteristics of their freeze-dried powder as a dry powder inhaler (DPI) were evaluated. Methods: To prepare PLGA LPPs, a double emulsification-solvent evaporation method was optimized and gentamicin sulfate was post-loaded in the LPPs. In vitro characteristics including morphological features, thermal behavior, aerodynamic profile and cumulative drug release were evaluated by the scanning electron microscope (SEM), differential scanning calorimetry (DSC), next-generation cascade impactor (NGI) and Franz diffusion cell respectively. Results: The obtained results revealed that the preparation method was capable to produce spherical large homogenous highly porous particles. 94% of gentamicin sulfate released from LPPs up to 30 minutes. Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) were 4.9 µm and 39% respectively. Conclusion: In this study, dry powder formulation composed of PLGA LPPs encapsulating gentamicin sulfate showed a promising in vitro behavior as a pulmonary delivery carrier. Improvements on the aerodynamic behavior and in vivo evaluations recommended for further developments.

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