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The use of inhalable nanoparticulate-based systems in the treatment of lung cancer allows for efficient localized delivery to the lungs with less undesirable systemic exposure. For this to be attained, the inhaled particles should have optimum properties for deposition and at the same time avoid pulmonary clearance mechanisms. Drug delivery to solid tumors is furthermore challenging, due to dense extracellular matrix (ECM) formation, which hinders the penetration and diffusion of therapeutic agents. To this end, the aim of the current work is to develop an ECM-modulating nano-structured microparticulate carrier, that not only enables the delivery of therapeutic nanoparticles (NPs) to the lungs, but also enhances their intratumoral penetration. The system is composed of acetalated maltodextrin (AcMD) NPs embedded into a water-soluble trehalose/leucine matrix, in which collagenase was loaded with different mass concentrations (10 %, 30 % and 50 %). The collagenase-containing AcMD nano-structured microparticles (MPs) exhibited suitable median volume diameters (2.58 ± 1.35 to 3.01 ± 0.68 µm), hollow corrugated morphology, sufficient redispersibility, low residual moisture content (2.71 ± 0.17 % to 3.10 ± 0.20 %), and favorable aerodynamic properties (Mass median aerodynamic diameter (MMAD): 1.93 ± 0.06 to 2.80 ± 0.10 µm and fine particle fraction (FPF): 68.02 ± 6.86 % to 69.62 ± 2.01 %). Importantly, collagenase retained as high as 89.5 ± 6.7 % of its enzymatic activity after spray drying. MPs containing 10 % mass content of collagenase did not show signs of cytotoxicity on either human lung adenocarcinoma A549 cells or lung MRC-5 fibroblasts. The nanoparticle penetration was tested using adenocarcinoma A549/MRC-5 co-culture spheroid model, where the inclusion of collagenase resulted in deeper penetration depth of AcMD-NPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Exploiting materials for nanoparticle production has never halted to address the diversity in cargos and applications. Herein, maltodextrin (MD) was selected for being economic, nontoxic, biocompatible, and biodegradable. Different MDs were modified through acetal modification, turning the polymer hydrophobic and allowing pH-dependent tunable degradability. The synthesized acetalated MD (AcMD) polymers exhibited different thermal decomposition profiles and lower glass transition temperatures. Nanoprecipitation yielded uniform AcMD nanoparticles (NPs) with diameters ranging from 141 to 258 nm. The particles were loaded with hydrophobic model drug, resveratrol (67.86% entrapment efficiency and 3.75% drug loading). The degradation and the in vitro release were studied at pH 7.4 and pH 5.0 and revealed different kinetics in dependence on the amount of cyclic/acyclic acetalation. Cell viability and cellular interaction were studied on adenocarcinoma human lung epithelial A549 and differentiated human monocytic THP-1 cells. The AcMD-NPs were well tolerated by both cell lines but exhibited different uptake behaviors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the current study, the transdermal route has been investigated to deliver the poorly bioavailable drug; curcumin into the systemic circulation, aiming to target both superficial and subcutaneous tumors such as the breast tumors. Accordingly, different colloidal carriers viz. ultradeformable nanovesicles comprising various penetration enhancers were exploited. Curcumin-loaded deformable vesicles were prepared by the thin film hydration method followed by extrusion. Sodium cholate and Tween 80 were set as standard edge activators and Labrasol, Transcutol, limonene and oleic acid were the penetration enhancers that were evaluated for their efficacy in skin permeation. The particle size and zeta potential of the prepared vesicles were significantly affected by the type of surfactant/penetration enhancer. The polydispersity measurements showed uniform particle size distribution indicating the sufficiency of the extrusion cycles performed. Curcumin, as a hydrophobic molecule, was well accommodated within the lipid bilayers of the prepared vesicles with entrapment efficiency (EE%) percentages and drug loading percentages (DL%) as high as 93.91% and 7.04%, respectively. The ex-vivo permeation studies were performed on male albino mice skin mounted on Franz diffusion cells. Oleic acid and Transcutol exhibited comparable fluxes to sodium cholate and Tween 80 (∼16 μg cm -2  h -1 ), whereas the fluxes of Labrasol and limonene were significantly lower. Cytotoxicity studies were performed using MTT assay on human breast cancer cell lines (MCF-7 cells). The results of the MTT assay demonstrated that oleic acid ultradeformable nanovesicles scored an IC 50 of 20 μg/ml which introduce these new curcumin-loaded nanovesicles as a successful delivery system for breast cancer therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Curcumin-loaded chitosan nanoparticles intended for transdermal delivery were successfully prepared, optimized and their fate, interaction and pathway through the skin were tracked. D-optimal response surface methodology was used for the nanoparticles optimization. Xy and z-stack confocal laser scanning microscopic images were used for the particles tracking after measuring the drug permeation through the skin using Franz diffusion cells. Very small particle sizes in the range of 33.85-199.23nm accompanied with low PDI values of 0.129-0.536 of the prepared curcumin-loaded chitosan nanoparticles were obtained. TEM images revealed the spherical and non-aggregating curcumin-loaded chitosan nanoparticles. The ex-vivo permeation studies have proven the ability of the prepared chitosan nanoparticles to deliver curcumin through the skin reaching fluxes viz 5.14±1.31μgcm -2 h -1 . The confocal laser scanning microscopy has proven that the appendageal route is the main route of penetration of the prepared nanoparticles and has demonstrated the localization of the chitosan nanoparticles within the hair follicles from which the drug diffuses to deep layers of the skin and beyond., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study is to utilize statistical designs and mathematical modeling to end the continuous debate about the different variables that influence the production of nanoparticles using the ionic gelation method between the biopolymer chitosan (CS) and tripolyphosphate (TPP) ion. Preliminary experiments were adopted to extract the optimum conditions for the nanoparticles preparation and model construction. Critical process parameters were screened using the one-factor-at-a-time (OFAT) approach to select optimum experimental regions. Finally, these factors were optimized using two different methods of response surface modeling; the Box-Behnken and the D-optimal. The significant models showed excellent fitting of the data. The two methods were validated using a set of check points and were subsequently compared. Good agreement between actual and predicted values was obtained though the D-optimal model was more successful in predicting the particle size of the prepared nanoparticles with percentage bias as small as 1.49%. Nanoparticles were produced with diameters ranging from 52.21 nm to 400.30 nm, particle polydispersity from 0.06 to 0.40 and suitable morphology. This work provides an overview on the production of chitosan nanoparticles with desirable size enabling their successful use in drugs delivery and targeting or in any nanotechnology or interfacial application., (Copyright © 2013 Elsevier B.V. All rights reserved.)