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Background: Recently, several strategies have been proposed for skin cancer therapy by transdermal delivery, and particularly the use of nanotechnology. Methods: This process disrupts the stratum corneum to deliver a drug through the skin, allowing it to accumulate at the tumor site. Results: Nanogels are drug delivery systems that can be applied to many diseases. Nanogel engineering has been widely studied for use in drug delivery, particularly in cancer theranostics. This review summarizes specific strategies for using nanogels to treat skin cancer, a topic that is limited in recent literature. Conclusion: Advanced techniques for effective skin cancer therapy based on the nanogel’s penetration and cellular uptake abilities will be discussed. Moreover, techniques for penetrating the skin, as well as drug release, permeation studies, and microscopic observations, will also be discussed.

The application of single-walled carbon nanotubes (SWCNTs) as drug carriers is limited by their poor dispersal in aqueous medium. This study aimed to prepare chitosan (CS)-modified SWCNTs (CS-SWCNTs) and to evaluate their physicochemical properties and cytotoxicity. Oxidized SWCNTs (O-SWCNTs) were prepared with the use of strong acid, and the effects of acidizing conditions on the oxidation degree of the O-SWCNTs were investigated. CS was then non-covalently modified on the surfaces of O-SWCNTs. O-SWCNTs and CS-SWCNTs were characterized through ultraviolet spectroscopy, Fourier transform-infrared spectroscopy, Raman spectroscopy, and transmission electron microscopy. The cytotoxic effects of the functionalized SWCNTs were determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. O-SWCNTs with relatively complete structure were successfully synthesized through 5 h of treatment with 5 M acid. The amine group of the CS and the carboxyl group of O-SWCNTs interacted in CS-SWCNTs. The functionalized SWCNTs did not aggregate or precipitate in water and exerted no cytotoxic effects on A549 and MCF-7 tumor cells. The CS-SWCNTs possess the advantages of a simple preparation process, excellent water dispersibility, and biocompatibility for drug loading.

Sprouted grains, which is a natural polysaccharide, is the subject of increasing scientific interest due to many benefits for human health. The aim of the present work was to develop sprouted rice (SR) as a safe and useful material for application in dissolution enhancement of anticancer poorly water-soluble drugs such as curcumin by solid dispersions (SDs). SDs were prepared with pure SR and modified sprouted rice (MSR) by the melting method. The dissolution rate, drug crystallinity changes, molecular interactions and wettability were characterized and compared between the formulations. The use of MSR could result in a promising system for improving the dissolution rate of poorly water-soluble drugs. MSR could induce a greater amorphous state and improved wettability of drugs for dissolution enhancement compared to SR. Although both SR and MSR showed hydrogen bonding interaction, insignificant differences between SR and MSR were observed. We found that the crystallinity, interactions and wettability of the drug were significantly affected and modulated by MSR.

The aims of this work were to design pH-independent controlled release (CR) tablet containing nanonizing solid dispersion (SD) adsorbed on hydrophilic silica (Aeroperl®300/30). Valsartan (VAL) was chosen to simultaneously modulate solubility and release rate due to its poor water solubility in low pH condition and short elimination half-life. Based on extensive equilibrium solubility and compatibility studies, poloxamer 407 was selected as a SD carrier. The melted mixtures of drug and poloxamer 407 were adsorbed onto hydrophilic fumed silica (Aeroperl®300/30). Ternary SD system changed crystalline drug into an amorphous state and had intermolecular hydrogen bonding as confirmed by FT-IR with poloxamer 407. The dissolution rate of SD system was markedly enhanced as compared with pure VAL or commercial Diovan®tablet in simulated gastric fluid (pH 1.2). Interestingly, the particle size of SD system was gradually nanonized for 2 hr, ranging from 600 nm to 150 nm during dissolution process. The SD-loaded CR (SD-CR) tablets using hydroxypropylmethylcellulose (HPMC 4000) showed pH-independent zero-order release and good stability at accelerated conditions for six months. The SD-CR tablet showed minimized inter-subject variation of maximum plasma concentration as compared with commercial Diovan®tablets in healthy human volunteers.

New blends of hydroxypropylmethylcellulose (HPMC, 4000 cps) and Gelucire®44/14 (GE) were utilized to modulate the solubility and release rate of poorly water-soluble drug in a controlled manner. HPMC was used as sustained release polymer while GE was blended as a solubilizing carrier. The binary blends of HPMC and GE with proportional ratios (0, 25, 50, 70, 100%) were prepared by three different preparation methods: simple physical mixing, solvent evaporation and hot-melting. The physical properties such as surface morphology, thermal behavior and crystallinity pattern of the binary blends without loading drugs were then characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), respectively. Finally, the ternary solid dispersions (SD) were prepared by dispersing model drugs in a binary blend. Two model drugs, water-soluble acetaminophen (AAP) and poorly water-soluble pranlukast (PLK) were applied to the binary blends. In case of AAP, HPMC retarded release rate but GE had no significant solubilizing effect due to the high AAP solubility, In contrast, the release rate of PLK was efficiently modulated release rate in a controlled manner with an aid of HPMC and GE. Surely, GE could play a key role in enhancing the dissolution rate while HPMC efficiently controlled release rate of drugs without losing drug crystallinity.

The aim of this study was to develop esomeprazole magnesium (EMZ-Mg) enteric-coated pellets and pellet-based tablets, as well as to investigate the effects of pellet size and compression method on acid tolerance, content uniformity, compressibility, and stability of preparations. This study used two types of pellet cores, namely, microcrystalline cellulose (MCC) core with a particle size of 150–300 μm and sucrose core with a particle size of 600–700 μm. Enteric-coated pellets, which consisted of a drug-free core, a drug layer, a sub-coating layer (hydroxypropyl methylcellulose, 6 cps), and an enteric-coating layer (Eudragit®L30D-55), were prepared by using a bottom-spray fluidized bed-coating technique. Pellet-based tablets were prepared by using a direct compression method or a wet granulation method. The acid tolerances of the two types of enteric-coated pellets (MCC and sucrose cores) reached up to 98% in simulated gastric fluid (pH 1.0) within 2 h, and the dissolution rates in simulated intestinal fluid (pH 6.8) reached up to 85% of the labeled amount within 15 min. When compressed into tablets, the pellets based on MCC core (smaller particle size) displayed a significantly higher acid tolerance (up to 92%) compared with the pellets based on sucrose core (larger particle size). In addition, the MCC core-based tablets (F8), especially those prepared by using a granulation method, showed higher drug content uniformity and compressibility than the sucrose core-based tablets (F10), and no lamination phenomenon was observed during compression. The crystallinity of EMZ-Mg was altered during drug layering process, and some physicochemical interactions were observed between the drug and excipients. Moreover, the two types of enteric-coated pellets showed a relatively high stability after storage under high temperature and strong light. However, they showed poor stability under high humidity, resulting in remarkable degradation of active compound. The EMZ-Mg enteric-coated pellets and pellet-based tablets were successfully developed, and reduction in pellet size and wet granulation reduced the differences in content uniformity and better protected the pellet coating from damages during compression.

The aim of this new work was to improve the dissolution rate of poorly water-soluble cilostazol (CLT) by adsorbing dissolved drug molecules onto the surface of undissolved carriers via reprecipitation and deposition process as the solvent (methylene chloride) was evaporated. The adsorption mixtures of CLT with Aerosil 300 and lactose monohydrate provided better drug dissolution rate as compared to mannitol. However, Aerosil-based adsorption powders were unable to be compressed into tablet due to low and unsatisfactory compressibility. The optimized CLT-loaded tablets containing lactose-based adsorption powders displayed almost complete dissolution within 90 min and showed significantly higher dissolution in intestinal fluid (pH 6.8) containing 0.2% sodium lauryl sulfate than the control tablet and the commercial reference product Pletaal®(Otsuka). Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) indicated that the crystalline property of CLT remained in adsorption powders with diminutive peak intensity. Fourier transform infrared spectroscopy (FT-IR) spectra indicated that the intermolecular hydrogen bond was formed between drug molecule and lactose monohydrate. Field-emission scanning electron microscope (Fe-SEM) clearly confirmed that CLT crystals with reduced size around 10 μm were adsorbed and deposited onto the surface of adsorbent material.

The combination of immunotherapy and chemotherapy is becoming a very promising cancer treatment method. However, the effective delivery of chemical drug or immune molecule to targeting tissues is a scientific issue to be solved urgently. A novel core–shell structure of single-walled carbon nanohorns (SWCNHs) and pH-sensitive liposome (PSL) was constructed for doxorubicin (DOX) and tumor-associated macrophage (TAM) polarization factor interleukin-21 (IL-21) codelivery in this study. The physicochemical properties, cytotoxicity, cellular uptake, macrophage polarization, and antitumor efficacy of functionalized nanocarriers were fully evaluated. DOX was incorporated into oxidized SWCNHs via π–π interaction (DOX-O-SWCNH) and then coated with IL-21-loaded PSL to obtain IL-21-loaded PSL (IL-21-PSL)-DOX-O-SWCNHs. The release rates of IL-21 and DOX from functionalized nanocarriers at the pH 7.4 of were lower than those at the pH of 5.5, thereby indicating a pH-sensitive drug release. Blank nanocarriers showed relatively low cytotoxicity to A549 cells and 293T cells. The half maximal inhibitory concentration (IC50) value of PSL-DOX-O-SWCNHs for A549 cells was 164.85 μg/mL. The PSL-DOX-O-SWCNHs can be effectively uptaken by A549 cells and the IL-21-PSL-DOX-O-SWCNHs can significantly downregulate the expression of M2 macrophage-related factors (IL-10 levels) and upregulate that of M1 macrophage-related factors (iNOs levels). The IL-21-PSL-DOX-O-SWCNHs also showed significantly high tumor targeting and distribution and significantly low tumor volume of A549 lung cancer cell-bearing nude mice, showing the cooperating effects of DOX and IL-21. The functionalized nanocarriers were mainly distributed in the tumor tissues and liver and less in the spleen, lung, and heart of mice. In conclusion, the functionalized IL-21-PSL-DOX-O-SWCNHs showed high drug loading, excellent cellular uptake, pH-sensitive release, TAM polarization, and remarkable antitumor efficacy in vivo.

The aim of this study was to develop an innovative fixed-dose combination (FDC) containing the sustained release of acetaminophen (AAP) and solubilized ibuprofen (IBF) using double-melt extrusion (DME) technology. The hot-melt extrusion (HME)-based formulation of AAP was screened by seven types of polymers (Polyvinyl alcohol, polyvinylpyrrolidone (Kollidon 30), polyvinyl acetate-polyvinylpyrrolidone mixture (Kollidon SR), hydroxypropyl cellulose (Klucel™ LF, Klucel™ HF), ethylcellulose (Aqualon™ N7, Aqualon™ N100). Poloxamer, polyethyleneglycol (PEG), and (meth)acrylate copolymers (Eudragit E PO, Eudragit E 100) were screened to optimize the IBF composition of the final DME formulations. Based on the transition temperature of the polymers, single-melt extrudates (SME) with AAP and Klucel™ LF were processed into pellets in a core, and the AAP SME pellets were covered with second extrudates of IBF and Eudragit E PO to achieve the final DME formulations. TGA, PXRD, and FT-IR analyses were employed to determine the physicochemical characteristics of the formulations containing APIs. These analyses were to evaluate the potential impact of the HME manufacturing process on the crystalline state of each API and to assess their stability when subjected to the temperatures involved in HME processing. Reference products, raw APIs, physical mixtures, and HME-based formulations were analyzed using a pH-shift dissolution method to compare the drug release behavior. Structural analysis of drug distribution was also performed using confocal laser scanning microscopy (CLSM) with different fluorescent dyes. As the DME extrudates were manufactured in a two-stage process, the green color for coumarin-6 (for AAP) added in the first HME process could easily be distinguished from rhodamine B (for IBF) that was added in the second HME. Furthermore, the dissolution rate of IBF in DME increased 6.7 times compared to the Raw API. Additionally, the AAP in DME formulation constantly released a 65.2% drug for 2 h without any fluctuations or interruptions. Consequently, these findings suggested that different drugs in one dosage form could be combined to achieve sustained release as well as immediate release with solubilizing effects using DME technology.