Water-soluble Anticancer Drug Research Articles

A novel nanodrug for the sensitization of photothermal chemotherapy for breast cancer in vitro.

Owing to the complexity of tumor treatment, clinical tumor treatment has evolved from a single treatment mode to multiple combined treatment modes. Reducing the tolerance of tumors to heat and the toxicity of chemotherapy drugs to the body, as well as increasing the sensitivity of tumors to photothermal therapy and chemotherapy drugs, are key issues that urgently need to be addressed in the current cancer treatment. In this work, polylactic acid-based drug nanoparticles (PLA@DOX/GA/ICG) were synthesized with good photothermal conversion ability by encapsulating the water-soluble anticancer drug doxorubicin (DOX), photothermal conversion agent indocyanine green (ICG) and liposoluble drug gambogic acid (GA) using a double emulsion method. The preparation process of PLA@DOX/GA/ICG was examined. Gambogic acid entrapped in PLA@DOX/GA/ICG nanoparticles could act as an HSP90 protein inhibitor to achieve bidirectional sensitization to chemotherapy and photothermal therapy under 808 nm laser irradiation for the first time, effectively ablating breast cancer cells in vitro. This nanodrug was expected to be used for the efficient treatment of tumors.

Dual stimuli-responsive polymeric nanoparticles combining soluplus and chitosan for enhanced breast cancer targeting.

A dual stimuli-responsive nanocarrier was developed from smart biocompatible chitosan and soluplus graft copolymers. The copolymerization was investigated by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), and Fourier transform infrared (FTIR). The optimized chitosan-soluplus nanoparticles (CS-SP NPs) were further used for the encapsulation of a poorly water-soluble anticancer drug. Tamoxifen citrate (TC) was used as the model drug and it was loaded in CS-SP NPs. TC CS-SP NPs were characterized in terms of particle size, zeta potential, polydispersity, morphology, encapsulation efficiency, and physical stability. The nanoparticles showed homogenous spherical features with a size around 94 nm, a slightly positive zeta potential, and an encapsulation efficiency around 96.66%. Dynamic light scattering (DLS), in vitro drug release, and cytotoxicity confirmed that the created nano-system is smart and exhibits pH and temperature-responsive behavior. In vitro cellular uptake was evaluated by flow cytometry and confocal microscopy. The nanoparticles revealed a triggered increase in size upon reaching the lower critical solution temperature of SP, with 70% of drug release at acidic pH and 40 °C within the first hour and a 3.5-fold increase in cytotoxicity against MCF7 cells incubated at 40 °C. The cellular uptake study manifested that the prepared nanoparticles succeeded in delivering drug molecules to MCF7 and MDA-MB-231 cells. In summary, the distinctive characteristics provided by these novel CS-SP NPs result in a promising nano-platform for effective drug delivery in cancer treatment.

Pegylated magnetic carbon nanotubes for efficient and safe delivery of poorly water-soluble platinum anticancer drugs

In this work, a new PEGylated magnetic carbon nanotube was developed for efficient and safe delivery of poorly water-soluble platinum anticancer drugs. Nanocarriers based on PEGylated magnetic carbon nanotubes were chemically synthesized through simple methods and finally platinum(II) complex conjugated to the synthesized delivery system (carbon nanotubes/polyethyleneglycol@Fe3O4/CPTMS@Cis-dichloro-bis(5-(4-pyridyl)-5-phenylhydantoin)platinum(II)) (CNTs/PEG@M/CPTMS@CisPt(II)). This nanomaterial was characterized by Transmission electron microscopes (TEM), Scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDS), X-Ray diffraction analysis (XRD), Ultraviolet–visible (UV–Vis) spectroscopy, Inductively coupled plasma mass spectrometry (ICP-MS), Fourier-transform infrared spectroscopy (FT-IR), Elemental mapping, Raman spectroscopy, and Nuclear Magnetic Resonance (NMR) analysis. The pattern of drug release from the CNTs/PEG@M/CPTMS@CisPt(II) was affected by pH at a certain temperature and time. In vitro cytotoxicity studies shown that despite the acceptable biocompatibility of the drug-free carrier, the drug-conjugated carrier has a good efficiency in limiting the growth and killing cancer cells. These findings revealed that CNTs/PEG@M/CPTMS@CisPt(II) carrier may provide a promising approach for delivery of the anticancer drugs to cancer cells.

Comprehensive NMR Investigation of Imidazolium-Based Ionic Liquids [BMIM][OSU] and [BMIM][Cl] Impact on Binding and Dynamics of the Anticancer Drug Doxorubicin Hydrochloride.

For the design of an efficient drug delivery system utilizing an ionic liquid (IL) as a carrier, it is prudent to gain molecular/atomistic level insights of a drug with IL in terms of binding and dynamics. In this scenario, the influence of anionic counterpart of imidazolium-based ILs, namely, 1-butyl-3-methyl-imidazolium octyl sulfate [BMIM][OSU] and 1-butyl-3-methyl-imidazolium chloride [BMIM][Cl] in their submicellar region ([IL] = 20 mM) on the model water-soluble anticancer drug doxorubicin hydrochloride (DOX) was probed by employing an arsenal of nuclear magnetic resonance (NMR) approaches. The salient feature of the present study includes the significant interaction of DOX with [BMIM][OSU], whereas the lack of such an interaction with [BMIM][Cl] is gauged by 1H NMR translation self-diffusometry and is further corroborated by 13C chemical shift perturbation. The two-step model was utilized to estimate the bound fraction (pb) and equivalent partition coefficient (K) of DOX with [BMIM][OSU]. A combination of selective and nonselective spin-lattice relaxation rates (R1SEL and R1NS, respectively) enables to gauze the significant interaction of DOX with [BMIM][OSU] over [BMIM][Cl]. Furthermore, 1D transient and truncated driven nuclear Overhauser enhancement (NOE) data analyses in the initial rate limit permits the evaluation of the cross-relaxation efficacy of DOX with the investigated ILs. An Arrhenius-type temperature dependence of the drug's self-diffusion was observed for DOX, DOX-[BMIM][OSU], and DOX-[BMIM][Cl] aqueous mixtures and the corresponding activation energies were evaluated.

Development of Amphiphilic Short Peptides to Control Drug Inclusivity through Metal Complexation Reactions

We previously reported that amphiphilic peptides containing one Lys and two His in the hydrophilic domain—KHHAAAAAA7 (KHHA7)—formed ternary complexes with intermediate metal ions and a poorly water-soluble anticancer drug—paclitaxel (Ptx)—which improved the water dispersibility of Ptx. In this study, the effect of ternary complexes of KHHA7 on cell viability is evaluated in vitro using HeLa cells. The ternary complexes reduced the cell viability by approximately 60%, suggesting that complex formation enhanced the cytotoxicity by increasing the water dispersibility of Ptx. Furthermore, the novel amphiphilic short peptides KHHAAAAAAW (KHHA6W) and KHHAAAWAAA (KHHA3WA3) were synthesized by Fmoc solid phase synthesis as dispersants for Ptx. These peptides differed from KHHA7 owing to the presence or absence of Trp and its position. The change in amino acid residues from Ala to Trp and the position of Trp in the hydrophobic domain of the amphiphilic peptide had little effect on the water dispersibility of Ptx.

GPP-TSAIII nanocomposite hydrogel-based photothermal ablation facilitates melanoma therapy

ABSTRACT Background Photothermal therapy (PTT) is a promising cancer treatment, but its application is limited by low photoconversion efficiency. In this study, we aimed to develop a novel graphene oxide (GO)-based nanocomposite hydrogel to improve the bioavailability of timosaponin AIII (TSAIII) while maximizing PTT efficacy and enhancing the antitumor effect. Methods GO was modified via physical cross-linking with polyvinyl alcohol. The pore structure of the gel was adjusted by repeated freeze-thawing and the addition of polyethylene glycol 2000 to obtain a nanocomposite hydrogel (GPP). The GPP loaded with TSAIII constituted a GPP-TSAIII drug delivery system, and its efficacy was evaluated by in vitro cytotoxicity, apoptosis, migration, and uptake analyses, and in vivo antitumor studies. Results The encapsulation rate of GPP-TSAIII was 66.36 ± 3.97%, with slower in vitro release and higher tumor cell uptake (6.4-fold) compared to TSAIII. GPP-TSAIII in combination with PTT showed better bioavailability and antitumor effects in vivo than did TSAIII, with a 1.9-fold higher tumor suppression rate than the TSAIII group. Conclusions GPP is a potential vehicle for delivery of TSAIII-like poor water-soluble anticancer drugs. The innovative PTT co-delivery system may serve as a safe and effective melanoma treatment platform for further anticancer translational purposes.

Development of multi-functionalized graphene oxide based nanocarrier for the delivery of poorly water soluble anticancer drugs

Development of multi-functionalized graphene oxide based nanocarrier for the delivery of poorly water soluble anticancer drugs

Electrospun self-emulsifying core-shell nanofibers for effective delivery of paclitaxel.

The poor solubility of numerous drugs pose a long-existing challenge to the researchers in the fields of pharmaceutics, bioengineering and biotechnology. Many "top-down" and "bottom-up" nano fabrication methods have been exploited to provide solutions for this issue. In this study, a combination strategy of top-down process (electrospinning) and bottom-up (self-emulsifying) was demonstrated to be useful for enhancing the dissolution of a typical poorly water-soluble anticancer model drug (paclitaxel, PTX). With polyvinylpyrrolidone (PVP K90) as the filament-forming matrix and drug carrier, polyoxyethylene castor oil (PCO) as emulsifier, and triglyceride (TG) as oil phase, Both a single-fluid blending process and a coaxial process were utilized to prepare medicated nanofibers. Scanning electron microscope and transmission electron microscope (TEM) results clearly demonstrated the morphology and inner structures of the nanofibers. The lipid nanoparticles of emulsions after self-emulsification were also assessed through TEM. The encapsulation efficiency (EE) and in vitro dissolution tests demonstrated that the cores-shell nanofibers could provide a better self-emulsifying process int terms of a higher EE and a better drug sustained release profile. Meanwhile, an increase of sheath fluid rate could benefit an even better results, suggesting a clear process-property-performance relationship. The protocols reported here pave anew way for effective oral delivery of poorly water-soluble drug.

Structural Determination of the Nanocomplex of Borate with Styrene-Maleic Acid Copolymer-Conjugated Glucosamine Used as a Multifunctional Anticancer Drug.

The development of effective anticancer drugs is essential for chemotherapy that specifically targets cancer tissues. We recently synthesized a multifunctional water-soluble anticancer polymer drug consisting of styrene-maleic acid copolymer (SMA) conjugated with glucosamine and boric acid (BA) (SGB complex). It demonstrated about 10 times higher tumor-selective accumulation compared with accumulation in normal tissues because of the enhanced permeability and retention effect, and it inhibited tumor growth via glycolysis inhibition, mitochondrial damage, and thermal neutron irradiation. Gaining insight into the anticancer effects of this SGB complex requires a determination of its structure. We therefore investigated the chemical structure of the SGB complex by means of nuclear magnetic resonance, infrared (IR) spectroscopy, and liquid chromatography-mass spectrometry. To establish the chemical structure of the SGB complex, we synthesized a simple model compound─maleic acid-glucosamine (MAG) conjugate─by using a maleic anhydride (MA) monomer unit instead of the SMA polymer. We obtained two MAG-BA complexes (MAGB) with molecular weights of 325 and 343 after the MAG reaction with BA. We confirmed, by using IR spectroscopy, that MAGB formed a stable complex via an amide bond between MA and glucosamine and that BA bound to glucosamine via a diol bond. As a result of this chemical design, identified via analysis of MAGB, the SGB complex can release BA and demonstrate toxicity to cancer cells through inhibition of lactate secretion in mild hypoxia that mimics the tumor microenvironment. For clinical application of the SGB complex, we confirmed that this complex is stable in the presence of serum. These findings confirm that our design of the SGB complex has various advantages in targeting solid cancers and exerting therapeutic effects when combined with neutron irradiation.

NMR Studies on the Interaction of Anticancer Drug Doxorubicin with Membrane Mimetic SDS.

In the formulation of efficient drug delivery systems, it is essential to unravel the structural and dynamical aspects of the drug's interaction with biological membranes. This has been done for the anticancer drug-membrane system comprising doxorubicin hydrochloride (DOX), a water-soluble anticancer drug, and the micellar sodium dodecyl sulfate (SDS), the latter serving as a useful mimic for membrane proteins. Using a multimodal NMR approach involving 1H, 2H, and 13C as probe nuclei and through the determination of chemical shifts, spin-relaxation, nuclear Overhauser enhancements (NOE), and translational self-diffusion (SD), the binding characteristics of the DOX with SDS have been determined. The perturbation to 13C chemical shifts of SDS indicate the penetration of DOX into the SDS micelle, which is further revealed by 1H-1H NOESY and SD measurements. 2H spin-relaxation measurements and their analysis using a two-step model show DOX induced SDS micellar volume changes, which determine the correlation times involved in the DOX-SDS mobility.

Cholesterol-Inulin Conjugates for Efficient SN38 Nuclear Delivery: Nanomedicines for Precision Cancer Therapy.

Simple SummarySevere limitations of conventional chemotherapy including unspecific biodistribution both at the tissue and cell organelle level have led to the necessity of developing precise and personalized therapeutic strategies. Accordingly, nanomedicine has aroused increased attention due to the versatility and precision of nano-sized drug delivery systems. One of the main advantage offered by well-designed nanoplatforms is the possibility to load, stabilize, and deliver (also at intracellular level) hydrophobic anticancer drugs, whose clinical use is strongly affected by their lower bioavailability. In this overview, the synthesis of polymeric nano-sized core-shell micelle-like nanostructures is a promising delivery strategy for hydrophobic drugs due to their excellent drug loading efficacy, stability in aqueous media, and versatile design. On these grounds, we developed stable and biodegradable inulin-based micelles for the delivery of SN38, chosen as a powerful poorly water-soluble anticancer drug. We designed an amphiphilic polysaccharide hydrophobized by partial functionalization with thiocholesterol moieties (INU-Cys-TC) via disulfide redox-sensitive bridges. We demonstrated that INU-Cys-TC can self-assemble into micelles at low concentration, encapsulating a high amount of SN38 (INU-Cys-TC@SN38) to be released in a sustained fashion. INU-Cys-TC@SN38 has proven to be capable of entering cancer and normal cells, releasing their payload, especially inside cell nuclei, where SN38 can act, providing the maximum inhibition of its molecular target. However, due to a different cell localization, INU-Cys-TC@SN38 was much more toxic for cancer cells, improving the SN38 selectivity, precision, and enhancing its anticancer effect not only toward colorectal cells, but also for breast cancer cells. This is a good example of drug repurposing due to innovative environment-sensitive delivery strategies. An amphiphilic inulin-thiocholesterol conjugate (INU-Cys-TC) was strategically designed as a biodegradable core-shell nanocarrier of 7-ethyl-10-hydroxy-camptothecin (SN38) to enhance its solubility and stability in aqueous media, thus exploiting its brilliant anticancer effect. INU-Cys-TC was designed to have the hydrophilic inulin backbone (external shell) partially functionalized with hydrophobic thiocholesterol moieties (internal core) through a biodegradable disulfide bond due to cysteamine bridges. Thiocholesterol moieties impair redox-sensitive self-assembling abilities, yielding to nano-sized micelles in aqueous media capable of efficiently encapsulating a high amount of SN38 (DL = 8.1%). Micelles (INU-Cys-TC@SN38) were widely characterized, demonstrating an effective and stable delivery strategy to overcome the poor water-solubility of SN38. SN38-loaded micelles showed a gradual and prolonged release of SN38 over time, and a cell- and time-dependent cytotoxicity. In particular, we show that micelles efficiently deliver SN38 inside cell nuclei, and, compared to normal cell lines, they can also enter cancer cells by endo-lysosomes, where a complete degradation can occur releasing the drug payload. Overall, the proposed micelles appear potentially effective as nanomedicines for precision cancer therapies of colorectal and breast cancer, thus improving the SN38 therapeutic index and extending its use in a huge plethora of cancers.

Synthesis, characterization, and micelle formation of novel PEGylated derivatives of noscapine with anti-cancer activity

In this work, regarding the poor water solubility of noscapine that limits its therapeutic effect, novel PEGylated derivatives of noscapine were synthesized via covalent crosslinking through a succinate linker. In order to study the effect of the PEG chain on the physicochemical properties and anti-cancer activity of the new compounds, different molecular weights of the PEG chain (1000, 4000, 6000 g/mol) were employed. The chemical structures of the synthesized compounds were characterized by 1HNMR, 13CNMR, HRMS, FT-IR, and UV–vis techniques. The micelle formation properties of the PEGylated compounds (CMC) were determined via the iodine UV-absorption method. The results exhibited that by increasing the PEG chain length, the CMC value was increased accordingly. The morphological analysis of the polymeric micelles via TEM showed spherical shapes with a mean particle size of 200–300 nm. In vitro cytotoxicity assay of the PEGylated derivatives of noscapine on MCF-7 breast cancer cells using MTT assay revealed that by increasing the water solubility of the PEGylated noscapine derivatives, the cytotoxicity effect enhanced dramatically from IC50 = 242.0 ± 1.01 µM for noscapine to 66.0 ± 0.43, 22.0 ± 0.23, and 15.0 ± 0.81 µM for PEGylated derivatives of 1000, 4000 and 6000 g/mol, respectively. It can be concluded that new PEGylated derivatives of noscapine with enhanced solubility may have the potential to be developed as a class of novel anticancer medicines. Moreover, they may provide a nano-delivery system for coadministration of low water-soluble anticancer drugs.

Investigation of self-assembled poly(ethylene glycol)-poly(L-lactic acid) micelle as potential drug delivery system for poorly water soluble anticancer drug abemaciclib

Polymer-based drug delivery systems have the ability to organize stable self-assembled nanocarriers containing hydrophobic cores allow to delivery of poorly water-soluble anticancer drugs by drug encapsulation process. Computational investigations can assist in designing of efficient drug-delivery systems. However, the high computational cost of simulation of nanocarrier self-assembly processes due to long-timescale required for equilibration are challenging. In this study we investigated the assembly mechanism of the abemaciclib anticancer drug encapsulated by the PEG-PLA copolymer micelle; molecular dynamics simulations were carried out for analyzing the aggregation of the PEG-PLA copolymer chains. The process of drug encapsulation is mostly operated by the hydrophobic and hydrophilic interactions. The hydrogen bonding and electrostatic interactions also play an important role in aggregation of the PEG-PLA copolymer chains. Analyses of radial distribution function and solvent accessible surface area show that the PEG-PLA copolymer micelles can increase the hydrophobic drugs solubility. The study presents insights into the mechanism of the structure of drug-loaded PEG-PLA copolymer micelles to design the drug delivery systems with helpful properties.

Fabrication of a pH-Responsive Magnetic Nanocarrier Based on Carboxymethyl Cellulose-Aminated Graphene Oxide for Loading and In-Vitro Release of Curcumin

In this study, a pH-responsive magnetic drug delivery system was prepared by cross-linking of Cofe2O4/graphene oxide to carboxymethyl cellulose (CMC) biopolymer with adipic acid dihydrazide (ADH) and then investigated for loading and release of a poorly water-soluble anti-cancer drug, curcumin (CUR). The CoFe2O4/GO-ADH-CMC bio-nanocomposite was characterized by FE–SEM/EDX, TEM, FT–IR, XRD, TGA, VSM, and zeta-potential techniques. The highest amount of drug loading was achieved as 23.7 mg g–1 at 323 K, pH 6.0, and 120 mg L–1 CUR concentration. The study of adsorption isotherms revealed that the Sips model was best fitted to the equilibrium data (R2 > 0.997 and RMSE < 0.48), which indicated the contribution of both chemisorption and physisorption in drug loading. Furthermore, the release profile of CUR from drug-loaded CoFe2O4/GO-ADH-CMC was studied in mimicking the endosomal (pH = 5.6) and physiological (pH = 7.4) conditions. After 24 h, the maximum cumulative releases were found to be 86 and 38% at pH = 5.6 and 7.4, respectively. Also, the Peppas-Sahlin kinetic model was followed for the release data. The MTT assay exhibited good biocompatibility of the CoFe2O4/GO-ADH-CMC. The results implied that CoFe2O4/GO-ADH-CMC magnetic bio-nanocomposite might be utilized as a potentially safe carrier with the continuous and slow release of CUR.Graphical Abstract

Functionalized Liposome and Albumin-Based Systems as Carriers for Poorly Water-Soluble Anticancer Drugs: An Updated Review.

Cancer is one of the leading causes of death worldwide. In the available treatments, chemotherapy is one of the most used, but has several associated problems, namely the high toxicity to normal cells and the resistance acquired by cancer cells to the therapeutic agents. The scientific community has been battling against this disease, developing new strategies and new potential chemotherapeutic agents. However, new drugs often exhibit poor solubility in water, which led researchers to develop functionalized nanosystems to carry and, specifically deliver, the drugs to cancer cells, targeting overexpressed receptors, proteins, and organelles. Thus, this review is focused on the recent developments of functionalized nanosystems used to carry poorly water-soluble drugs, with special emphasis on liposomes and albumin-based nanosystems, two major classes of organic nanocarriers with formulations already approved by the U.S. Food and Drug Administration (FDA) for cancer therapeutics.

Preparation of magnetic methotrexate nanocarrier coated with extracted hydroxyapatite of sea urchin (Echinometra mathaei)

New polymer-coated magnetic nanocarrier using magnetic iron oxide nanoparticles coated with chitosan and nanohydroxyapatite extracted from Sea urchin that both have anti-cancer properties showed good ability to Methotrexate (MTX) delivery. Iron oxide nanoparticles and hydroxyapatite prepared by co-precipitation and hydrothermal methods respectively. To stabilize the nanoparticles and optimization of the nanoparticles with hydroxyapatite, 3-chloropropyltrioethoxysilane and chitosan were performed. The water-soluble anticancer drug Methotrexate was selected as the drug model. The drug loading percentage was % 86.66, loading efficiency was % 99.5 and the polydispersity of the nanoparticles was 0.01. The kinetic pattern of drug release is consistent with the Peppas equation and the results of the thermal analysis confirm the stability of the crystalline form of the drug. The FTIR results and FE-SEM images showed that the nanoparticles were successfully prepared and coated and their size ranged from 30 nm to 1.5μm. The VSM analysis confirms the magnetic properties of the nanoparticles and the magnetic indices for the magnetic nanocarrier and the magnetic nanocarrier carrying MTX are 23 and 19 emu/g–1, respectively. The present study demonstrates the potential of iron oxide nanoparticles for the design of new magnetic nanocarrier and for guiding Methotrexate drug therapy in cancer chemotherapy.

Establishment and characterization of lung co‐culture spheroids for paclitaxel loaded Eudragit® RL 100 nanoparticle evaluation

3D cell cultures are regarded as a better and more relevant approach for screening drugs and therapeutics, particularly due to their likeness with the in vivo conditions. Spheroids offer an intermediate platform between in vitro and in vivo models, for conducting tumor-based investigations. In this study, a simple setup was developed for consistent generation of lung co-culture spheroids, which were developed using the cancer cell lines A549, NCI H460, and fibroblast cells WI-38. The potential of these spheroids for evaluating the toxicity of Eudragit® RL 100 nanoparticles (ENP) was explored. Monodisperse ENP, having the size range of 140-200 nm was prepared using the nanoprecipitation method. These were loaded with the poorly water-soluble anticancer drug paclitaxel. The evaluation of toxicity and uptake of drug-loaded ENP revealed that 2D monolayers were more sensitive to treatment than 3D spheroids. Within spheroids, co-cultures were more resistant to the treatment than monocultures. Overall, our findings demonstrated that the lung co-culture spheroids were a suitable model for accelerating the efficacy and toxicity-related investigations of novel drug delivery systems.

An experimental and computational study to evaluation of chitosan/gum tragacanth coated-natural lipid-based nanocarriers for sunitinib delivery

This study aimed to introduce two natural lipids including the fat tail (FT) and the local oil (Roghan Kermanshahi) in order to design lipid nanocarriers for loading of sunitinib malate as a poorly water-soluble anticancer drug. The drug-loaded solid lipid nanoparticles (SLNs) were fabricated using the modified solvent evaporation-ultrasonic combination method. Coating with chitosan and gum tragacanth (GT) was performed. The physicochemical properties of nanoparticles were analyzed by dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC) and scanning electron microscopy (SEM). Also, in vitro drug release and cytotoxicity effect was investigated. Furthermore, the atomic details of SLNs formation and drug encapsulation were investigated by the computational study. The results showed that polymer-FT-SLNs and polymer-Roghan-SLNs had the particle size in the nanometer range (below 150 nm) with the zeta potential values of higher than |−28 mV| and possessed high entrapment efficiency and loading content of sunitinib. The release of drugs from as prepared delivery systems has demonstrated a sustained release pattern, which was fitted to Higuchi’s kinetics. Prepared free SLNs had shown no cytotoxicity effect while sunitinib loaded SLNs had suitable cytotoxicity against acute myeloid leukemia cells (THP-1). The computational approach has demonstrated that the drug-lipid binding energies are higher in the FT system than RK. Our results indicated that the as-prepared chitosan/tragacanth encapsulated natural lipid SLNs can be a good drug nanocarrier for the hydrophobic anticancer drug.

Formulation and optimization of gefitinib-loaded nanosuspension prepared using a newly developed dendritic lipopeptide oligomer material

Amino acid derived polypeptides are often biocompatible, and hence the materials of choice in nanoparticle formulations to avoid nanotoxicity and associated complications. A hydrophilic linear polypeptide γ-poly(l-glutamic acid) can form self-assembled nanoparticles only when made amphiphilic by chemical modification. Present work investigated pharmaceutical feasibility of a newly synthesized l-glutamic acid-based dendritic lipopeptide oligomer, which was found to be biocompatible and devoid of any inherent anticancer activity in vitro. Gefitinib, a poorly water-soluble anticancer drug, was used as the model drug to prepare an oligomeric nanosuspension by solvent evaporation–ultrasonication method. The formulation was optimized using response surface methodology and Box–Behnken model of design of experiments. The optimized gefitinib-loaded oligomeric nanosuspension demonstrated acceptable particle-size distribution, surface morphology, colloidal stability, entrapment efficiency, and drug release profile. Overall, current work highlights competence of a newly synthesized dendritic lipopeptide oligomer for drug delivery applications.

Docetaxel-Loaded Poly(3HB-co-4HB) Biodegradable Nanoparticles: Impact of Copolymer Composition

Polyhydroxyalkanoate (PHA) copolymers show a relatively higher in vivo degradation rate compared to other PHAs, thus, they receive a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water-soluble anticancer drug docetaxel (DCX) were produced using poly(3-hydroxybutyrate-co-4-hydroxybutyrate), P(3HB-co-4HB), copolymers biosynthesised from Cupriavidus malaysiensis USMAA1020 isolated from the Malaysian environment. Three copolymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB-co-4HB). Blank and DCX-loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Preformulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in terms of average particle size around 150 nm and narrow particle size distribution (polydispersity index (PDI) below 0.100). The encapsulation efficiency result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX; DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticle system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug-to-polymer ratio while for the 30% and 40% drug-to-polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.