Preparation of thermoresponsive poly(N-vinylcaprolactam-co-2-methoxyethyl acrylate) nanogels via inverse miniemulsion polymerization

Stimuli-responsive polymeric nanogels hold great potential in biological applications. In this work, thermoresponsive polymeric nanogels were conveniently prepared through inverse miniemulsion polymerization of two monomers with a good biocompatibility, N-vinylcaprolactam and 2-methoxyethyl acrylate. A macromolecular crosslinker, poly(ethylene glycol) dimethacrylate (PEGDMA), was used to achieve a better thermoresponsiveness, compared with low-molecular-weight crosslinkers. The prepared poly(N-vinylcaprolactam-co-2-methoxyethyl acrylate) (poly(NVCL-co-MEA)) nanogels could be well redispersed in aqueous systems, displaying a reversible thermoresponsive transition behavior. The influences of the synthesis parameters including the emulsifier content, PEGDMA content, and monomer composition on the particle properties of poly(NVCL-co-MEA) nanogels both in inverse emulsions and in aqueous dispersions were systematically investigated. Furthermore, the impacts of the monomer composition and PEGDMA content on the thermoresponsiveness of poly(NVCL-co-MEA) nanogels were also studied. Promisingly, the introduction of MEA monomeric units to the copolymer chains only slightly reduced the thermoresponsiveness of poly(NVCL-co-MEA) nanogels. This feature allows to improve the biocompatibility of polymeric nanogels by using MEA as the comonomer without need to compromise the thermoresponsiveness of nanogels. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48237.     

Poly(hexylacrylate)Core‐poly(ethyleneglycol methacrylate)Shell nanogels as fillers for poly(2‐hydroxyethyl methacrylate) nanocomposite hydrogels

The preparation of poly(hexylacrylate)_core‐poly(ethyleneglycol methacrylate)_shell (PHA‐co‐PEGMA) nanogels, to be used as fillers in nanocomposite hydrogels, is reported. Stable nanogels with particle sizes between 90–300 nm were obtained varying the conditions of synthesis. The synthesis recipe of the nanogels could be easily scaled up. Purified and dispersed nanogels in aqueous solution were used as soft fillers for poly(2‐hydroxyethyl methacrylate) (PHEMA) hydrogels, crosslinked with ethylene glycol dimethacrylate (EGDMA). The obtained nanocomposite hydrogels exhibit a larger swelling capacity and a higher thermal stability in comparison with the non‐filled PHEMA hydrogels. Young, storage, and lost moduli, increase largely, in the better case up to 72.5% in the swollen state; while in the dry state the storage modulus increase up to 4.7 fold with a very low load on nanogels (0.64 wt%); resulting in biomaterials with improved properties with potential applications in medical devices. POLYM. ENG. SCI., 59:170–181, 2019. © 2018 Society of Plastics Engineers     

Curcumin Loaded Nanocarriers with Varying Charges Augmented with Electroporation Designed for Colon Cancer Therapy

(1) Background: The size and surface charge are the most significant parameters of nanocarriers that determine their efficiency and potential application. The poor cell uptake of encapsulated drugs is the main limitation in anticancer treatment. The well-defined properties of nanocarriers will enable to target specific tissue and deliver an active cargo. (2) Methods: In the current study, poly(D,L -lactide) (PLA) nanocarriers loaded with curcumin (CUR) and differing surface charge were evaluated for transport efficacy in combination with electroporation (EP) in dependence on the type of cells. The obtained CUR-loaded nanoparticles with diameters ranging from 195 to 334 nm (derived from dynamic light scattering (DLS)) were characterized by atomic force microscopy (AFM) (morphology and shape) and Doppler electrophoresis (ζ-potential) as well as UV-vis spectroscopy (CUR encapsulation efficiency (about 90%) and photobleaching rate). The drug delivery properties of the obtained PLA nanocarriers enhanced by electroporation were assessed in human colon cancer cells (LoVo), excitable normal rat muscle cells (L6), and free of voltage-gated ion channels cells (CHO-K1). CLSM studies, viability, and ROS release were performed to determine the biological effects of nanocarriers. (3) Results: The highest photodynamic activity indicated anionic nanocarriers (1a) stabilized by C₁₂(COONa)₂ surfactant. Nanocarriers were cytotoxic for LoVo cells and less cytotoxic for normal cells. ROS release increased in cancer cells with the increasing electric field intensity, irradiation, and time after EP. Muscle L6 cells were less sensitive to electric pulses. (4) Conclusions: EP stimulation for CUR-PLA nanocarriers transport was considered to improve the regulated and more effective delivery of nanosystems differing in surface charge.     

Preparation of xanthan gum nanogels and their pH/redox responsiveness in controlled release

Crosslinked xanthan gum nanogels with pH/Redox responsiveness were prepared through an amidation reaction of xanthan gum with cystamine tetra-hydrazide in aqueous solution by “one pot.” The structures and morphologies of the nanogels were characterized by Fourier transform infrared spectroscopy, proton magnetic resonance, dynamic light scattering, scanning electron microscope, and transmission electron microscope. It was found that the nanogels demonstrated good pH/redox dual-responsiveness due to the presence of disulfide bonds and both of amino and carboxyl groups in the polymers. Doxorubicin was loaded in the nanogels and the drug-controlled release was investigated. The disulfide bonds in the crosslinked structure could be reduced by glutathione solutions，leading to breakdown of the crosslinking structure and drug release. The nanogels were biocompatible and they had promising prospects as anti-cancer drug carriers for targeted release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47921.     

Surface‐active amphiphilic poly[(2‐acrylamido‐2‐methylpropanesulfonic acid)‐co‐(N‐isopropylacrylamide)] nanoparticles as stabilizer in aqueous emulsion polymerization

This work reports the effect of nanogel solid particles on the surface and interfacial tension of water/air and water/styrene interfaces. Moreover, the work aimed to use nanogels as a stabilizer for miniemulsion aqueous polymerization. A series of amphiphilic crosslinked N‐isopropylacrylamide (NIPAm) and 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS) copolymer nanogels were synthesized based on an aqueous copolymerization batch method. Divinylbenzene and N,N‐methylene bisacrylamide were used as crosslinkers. The morphologies of the prepared nanogels were investigated using transmission and scanning electron microscopies. The lower critical transition temperatures were determined using differential scanning calorimetry. The surface tension of colloidal NIPAm/AMPS dispersions was measured as functions of surface age, temperature and the morphology of the NIPAm/AMPS nanogels. The NIPAm/AMPS nanogels reduced the surface tension of water to about 30.1 mN m^?1 at 298 K with a small increase at 313 K. Surface activities of these nanogels in water were determined by surface tension measurements. The NIPAm/AMPS dispersions had high surface activity and were used as a stabilizer to prepare a crosslinked poly(styrene‐co‐AMPS) microgel based on emulsion crosslinking polymerization. © 2013 Society of Chemical Industry     

Synthesis and evaluation of luliconazole loaded biodegradable nanogels prepared by pH-responsive Poly (acrylic acid) grafted Sodium Carboxymethyl Cellulose using amine based cross linker for topical targeting: In vitro and Ex vivo assessment

ABSTRACT

Fungal infection in immuno compromised patients causes skin syndromes and problems. At Present, innovative alternatives are required to cure skin disorders and infections. Luliconazole is a novel, broad spectrum, imidazole antifungal agent. The purpose of this study was to develop biodegradable, pH responsive, chemically cross-linked and Poly (acrylic acid) grafted sodium carboxymethyl cellulose nanogels. Nanogels had been synthesized to evaluate its applicability as an effective carrier of luliconazole for topical (skin) targeting. Chemically cross-linked sodium carboxymethyl cellulose-grafted-Poly acrylic acid (NaCMC-g-PAA) was synthesized from acrylic acid and sodium carboxymethyl cellulose using N, N’-methylene bisacrylamide (cross-linker) and potassium persulfate (initiator) using free radical polymerization. Variation of reaction parameters such as pH, cross linker, initiator and temperature has been used to optimize the best one. The developed nanogels reveal significant pH sensitive drug releasing behavior. NaCMC-g-PAA nanogels has been characterized using various physicochemical characterization techniques. Nanogels characteristics were evaluated through the In vitro drug release, Ex vivo permeation study, Nuclear magnetic resonance spectroscopy, Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscope, Stability Study and antifungal activity. All batches were characterized for particle size analysis and ranged from 78.82 nm to 190 nm. The viscosity of developed nanogels was found to be 5941 cps. It was observed that the developed drug-loaded NaCMC-g-PAA nanogels were more effective in killing the fungus. Consequently, Nanogels incorporated with luliconazole could be a new approach with improved antifungal activity and increased topical delivery for a drug with poor aqueous solubility rather than coarse drug-containing cream.     

Peptide Amphiphilic Supramolecular Nanogels: Competent Host for Notably Efficient Lipase-Catalyzed Hydrolysis of Water-Insoluble Substrates

The present work depicts the development of stable nanogels in an aqueous medium that were exploited for efficient surface-active lipase-catalyzed hydrolysis of water-insoluble substrates. Surfactant-coated gel nanoparticles (neutral NG1 , anionic NG2 , and cationic NG3 ) were prepared from peptide amphiphilic hydrogelator ( G1 , G2 , and G3 , respectively) at different hydrophilic and lipophilic balance (HLB). Chromobacterium viscosum (CV) lipase activity towards hydrolysis of water-insoluble substrates (p-nitrophyenyl-n-alkanoates (C4–C10)) in the presence of nanogels got remarkably improved by ~1.7–8.0 fold in comparison to that in aqueous buffer and other self-aggregates. An increase in hydrophobicity of the substrate led to a notable improvement in lipase activity in the hydrophilic domain (HLB>8.0) of nanogels. The micro-heterogeneous interface of small-sized (10–65 nm) nanogel was found to be an appropriate scaffold for immobilizing surface-active lipase to exhibit superior catalytic efficiency. Concurrently, the flexible conformation of lipase immobilized in nanogels was reflected in its secondary structure having the highest α-helix content from the circular dichroism spectra.     

pH/redox/thermo-stimulative nanogels with enhanced thermosensitivity via incorporation of cationic and anionic components for anticancer drug delivery

To explore the potential biomedical applications of nanogels, it is a key factor to improve their thermosensitivity. In this paper, triple-responsive nanogels poly(N-isopropylacrylamide–N,N′-dimethylaminoethyl methacrylate–acrylic acid) (PNDA) were synthesized via in situ incorporating both cationic components and anionic components into a normal thermosensitive polymer matrix. The triple-monomer constructed PNDA nanogels displayed an enhanced thermosensitivity as compared with dual-monomer constructed PND nanogels. The PNDA nanogels presented higher encapsulation efficiency (～89%) and exhibited better pH/redox/thermo-responsivenesses in an anticancer drug delivery. In vitro biological study indicated that the PNDA nanogels have excellent biocompatibility and improved anticancer cytotoxicity to A549 cells after loading drug DOX.     

Antimicrobial Activity of Curcumin in Nanoformulations: A Comprehensive Review

Curcumin (CUR) is a natural substance extracted from turmeric that has antimicrobial properties. Due to its ability to absorb light in the blue spectrum, CUR is also used as a photosensitizer (PS) in antimicrobial Photodynamic Therapy (aPDT). However, CUR is hydrophobic, unstable in solutions, and has low bioavailability, which hinders its clinical use. To circumvent these drawbacks, drug delivery systems (DDSs) have been used. In this review, we summarize the DDSs used to carry CUR and their antimicrobial effect against viruses, bacteria, and fungi, including drug-resistant strains and emergent pathogens such as SARS-CoV-2. The reviewed DDSs include colloidal (micelles, liposomes, nanoemulsions, cyclodextrins, chitosan, and other polymeric nanoparticles), metallic, and mesoporous particles, as well as graphene, quantum dots, and hybrid nanosystems such as films and hydrogels. Free (non-encapsulated) CUR and CUR loaded in DDSs have a broad-spectrum antimicrobial action when used alone or as a PS in aPDT. They also show low cytotoxicity, in vivo biocompatibility, and improved wound healing. Although there are several in vitro and some in vivo investigations describing the nanotechnological aspects and the potential antimicrobial application of CUR-loaded DDSs, clinical trials are not reported and further studies should translate this evidence to the clinical scenarios of infections.     

Atom transfer radical polymerization in inverse miniemulsion: A versatile route toward preparation and functionalization of microgels/nanogels for targeted drug delivery applications

This short review describes application of atom transfer radical polymerization (ATRP) in inverse miniemulsion and disulfide–thiol exchange to prepare well-defined biodegradable functional nanogels (ATRP-nanogels). Due to the formation of uniform network, the ATRP-nanogels have higher swelling ratios, better colloidal stability, and controlled degradation, as compared to nanogels prepared by conventional free-radical polymerization. Various water-soluble biomolecules such as anticancer drugs, carbohydrates, proteins, and star branched polymers were incorporated into ATRP-nanogels at high loading level, by in-situ physical loading or by in-situ chemical incorporation via covalent bonds. The nanogels crosslinked with disulfide or polyester linkages were degraded either in the presence of biocompatible reducing agents or by hydrolysis for controllable release of the encapsulated drugs. ATRP-nanogels contain bromine end groups that enable further chain extension and functionalization with biorelated molecules. They are also easily functionalized by copolymerization with functional monomers or use of functional ATRP initiator during synthesis. These functional nanogels have capability to be further chemically modified and bioconjugated with cell-targeting proteins, antibodies, and integrin-binding peptides to increase cellular uptake via clathrin-mediated endocytosis. These results suggest that such well-defined functional nanogels have great potential for targeted drug delivery applications.     

Milk-Derived Exosomes as Nanocarriers to Deliver Curcumin and Resveratrol in Breast Tissue and Enhance Their Anticancer Activity

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encapsulation in milk-derived EXOs (EXO-CUR and EXO-RSV). A kinetic breast tissue disposition was performed in rats. CUR and RSV were analyzed using UPLC-QTOF-MS and GC-MS, respectively. Antiproliferative activity was tested in MCF-7 and MDA-MB-231 breast cancer and MCF-10A non-tumorigenic cells. Cell cycle distribution, apoptosis, caspases activation, and endocytosis pathways were determined. CUR and RSV peaked in the mammary tissue (41 ± 15 and 300 ± 80 nM, respectively) 6 min after intravenous administration of EXO-CUR and EXO-RSV, but not with equivalent free polyphenol concentrations. Nanomolar EXO-CUR or EXO-RSV concentrations, but not free CUR or RSV, exerted a potent antiproliferative effect on cancer cells with no effect on normal cells. Significant (p < 0.05) cell cycle alteration and pro-apoptotic activity (via the mitochondrial pathway) were observed. EXO-CUR and EXO-RSV entered the cells primarily via clathrin-mediated endocytosis, avoiding ATP-binding cassette transporters (ABC). Milk EXOs protected CUR and RSV from metabolism and delivered both polyphenols to the mammary tissue at concentrations compatible with the fast and potent anticancer effects exerted in model cells. Milk EXOs enhanced the bioavailability and anticancer activity of CUR and RSV by acting as Trojan horses that escape from cancer cells’ ABC-mediated chemoresistance.     

Glucose‐sensitive and blood‐compatible nanogels for insulin controlled release

For insulin delivery, many reported glucose‐sensitive materials are designed to response to the glucose in the blood. However, few particular studies on their blood compatibility have been reported. In this article, for controlled insulin release in diabetes therapy, a glucose‐sensitive nanogel was prepared through thermally initiated precipitation polymerization using the aminophenylboronic acid‐containing monomer to copolymerize with methacrylic acid. The obtained nanogels showed the uniform and spheroidal morphology as observed by SEM, and their sizes in aqueous solution are dependent on the concentration of glucose. Through in vitro and in vivo insulin release tests, it was found that nanogels showed the glucose‐dependent insulin release and prolonged effect of lowing blood glucose level. The blood compatibility of nanogels has also been explored through various assays including the hemolysis, activated partial thromboplastin time, prothrombin time as well as the thromboelastography. All results indicated that the obtained glucose‐sensitive nanogels showed good blood safety. Moreover, their low cytotoxicity suggested a potential application in diabetes therapy. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43504.     

pH sensitive supramolecular vesicles from cyclodextrin graft copolymer and benzimidazole ended block copolymer as dual drug carriers

Supramolecular assemblies from chitosan-graft-β-cyclodextrin (CS-g-CD) and benzimidazole ended poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL-BM) were formed based on the inclusion complexation between β-cyclodextrin and benzimidazole. The supra-amphiphiles self-assembled into complex vesicles with PCL/β-CD as the hydrophobic membrane, hydrophilic PEG and CS as the corona. The hydrophobic membrane and aqueous lumen of vesicles exhibited efficient entrapment both for hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX). The drug loading of vesicles was more than 20.2% and 38.4% for CUR and DOX, respectively. Decreasing pH to acidic condition or increasing temperature, more controllable and rapid release of two drugs was observed. Cytotoxicity assays revealed that dual drug-loaded vesicles retained high cell proliferation inhibition efficiency than free drugs.GRAPHICAL ABSTRACT     

Targeting of a Thermosensitive Nanogel Copolymerized With Macromonomer for Cell Uptake and Drug Controlled Release

In this study, N-isopropylacrylamide (NIPAAm), propyl acrylic acid (PAAC), and poly(N-isopropylacrylamide-co-undecylenic acid) acrylamide were introduced to synthesize PNIPAAm-based nanogels (NG). The morphology of NG particles was characterized via transmission electron microscopy (TEM). The nanogels exhibited a lower critical solution temperature (LCST) of 34°C and a temperature-induced drug release in vitro. After conjugation of arginine-glycine-aspartic acid (RGD)–containing peptide (GRGDS), the cellular uptake of doxorubicin (Dox)-loaded nanogel by HeLa cells had been greatly enhanced. The Dox molecules in endocytosed nanogels could be released efficiently at 37°C and subsequently kill tumor cells, suggesting that the nanogel has great potential for targeting delivery.     

One-step synthesis of pegylated cationic nanogels of poly(N,N′-dimethylaminoethyl methacrylate) in aqueous solution via self-stabilizing micelles using an amphiphilic macroRAFT agent

Cationic nanogels of Pegylated poly(N,N′-Dimethylaminoethyl methacrylate) (PEG-PDAEMA) have been synthesized in aqueous solution by a one-step surfactant-free reversible addition-fragmentation transfer (RAFT) process. A Pegylated amphiphilic macroRAFT agent (mPEG₅₅₀-TTC) with a hydrophobic dodecyl chain was utilized to stabilize the micelles and control the polymerization and crosslinking of DMAEMA in aqueous solution. ¹H NMR, GPC, Elemental analysis, Dynamic light scattering (DLS), Zeta potential and Atomic force microscopy (AFM) measurements confirmed the formation of the cationic nanogels in size of about 20 nm with a narrow distribution. It also revealed that the concentration of monomer and the kinds of crosslinker are the key factors to control the formation of nanogel. This cationic nanogel has potential application in gene delivery.     

Photoresponsive nanogels synthesized using spiropyrane‐modified pullulan as potential drug carriers

Reversible light‐responsive nanogels were constructed from an amphiphilic spiropyrane‐modified pullulan (SpP). The polymer was synthesized by modifying a biodegradable pullulan with carboxyl‐containing spiropyrane (Sp) molecules. The SpP structure was confirmed by the appearance of a carbonyl signal in the FT‐IR and ¹H NMR spectra. The nanogels can be controlled by photostimulation, which results in the reversible structural transformation of the hydrophobic Sp to the hydrophilic merocyanine. The physical properties of the nanogels were confirmed to change dramatically after being irradiated with different wavelengths of light. Drug delivery tests showed that the model drug pyrene was completely captured by the nanogels and then released from the SpP nanogels in a light‐dependent manner. This study provides an alternative approach to constructing light‐responsive nanocarriers with excellent biocompatibility for drug uptake and release. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40288.     

Temperature- and pH-sensitive core–shell nanogels as efficient carriers of doxorubicin with potential application in lung cancer treatment

Temperature- and pH-sensitive core–shell nanogels were prepared by one-pot soapless emulsion polymerization of N-isopropylacrylamide and 2-methacryloyloxy benzoic acid with the aid of a crosslinker (core) using poly(ethylene glycol) methyl ether methacrylate as stabilizer (shell). The size of nanogels depended on the crosslinker used, being considerable smaller (around 100?nm) with the use of the acid-labile crosslinker 9-divinyl-2,4,8,10-tetraoxaspiro[5.5]-undecane (DVA). Doxorubicine (DOX) was loaded in nanogels with good efficiency. The empty nanogels were biocompatible for a lung cancer cell line (NCI-H1437), while the DOX-loaded, DVA-crosslinked nanogels resulted with efficient cytotoxicity for that cell line.     

Synthesis of poly(N,N-dimethylaminoethyl methacrylate) nanogels in reverse micelles for delivery of plasmid DNA and small interfering RNAs into living cells

Hydrogel nanoparticles of poly(N,N-dimethylaminoethyl methacrylate) with hydrodynamic radii of 40?C50 nm are synthesized via the copolymerization of a water-soluble monomer and N,N??-methylenebis(acrylamide) in a solution of Brij-97 reverse micelles in cyclohexane. All amino groups of nanoparticles are protonated in a weakly acidic solution; however, almost one-third of them remain inaccessible to a flexible polystyrenesulfonate polyanion, while almost two-thirds of them remain inaccessible to rigid double-helical DNA. Complexes of nanogels with plasmid DNA carrying the firefly luciferase gene transfect eukaryotic cells in a cultural medium, and the products of interaction of nanogels with small interfering RNAs suppress expression of the marker enzyme. In both systems, the replacement of linear polyamine with nanogel significantly increases the efficiency of delivery. The activity of nanogels in transfection experiments depends in an extremum pattern on the crosslink degree and achieves a maximum value at a crosslinking-agent concentration of 5 mol %. The results of this study suggest that the developed procedure offers promise for the synthesis of cationic nanogels as vectors for delivery of genetic material into living cells.     

Enhanced therapeutic efficacy of clotrimazole by delivery through poly(ethylene oxide)-block-poly(ε-caprolactone) copolymer-based micelles

Amphiphilic block copolymers have been the subject of great scientific interests due to their applications in various fields including nano drug delivery. Three amphiphilic block copolymers based on poly(ε-caprolactone) as a hydrophobic segment and methoxy poly(ethylene oxide) ( as a hydrophilic part were synthesized by the ring-opening polymerization of ε-caprolactone using MeO-PEO_5K as macroinitiator by varying initial feed ratios. The synthesized polymers were further explored for their drug delivery potential using clotrimazole as model hydrophobic drug. Drug-loaded micelles were characterized for shape, size, drug encapsulation efficiency, in vitro release, and thermal stability using atomic force microscope, zetasizer, UV–visible spectrophotometry, FTIR, differential scanning calorimetry, and thermogravimetric analysis. Clotrimazole loaded in micelles were also investigated for its antifungal activity through an in vitro assay and scanning electron microscopy. The antifungal activity of drug increased significantly by delivering through polymeric micelles. Current study provides insight into different factors that can be maneuvered to achieve a variety of desired properties of micelles for improved therapeutic efficacy of drugs like clotrimazole. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47769.     

High-Payload Buccal Delivery System of Amorphous Curcumin–Chitosan Nanoparticle Complex in Hydroxypropyl Methylcellulose and Starch Films

Oral delivery of curcumin (CUR) has limited effectiveness due to CUR’s poor systemic bioavailability caused by its first-pass metabolism and low solubility. Buccal delivery of CUR nanoparticles can address the poor bioavailability issue by virtue of avoidance of first-pass metabolism and solubility enhancement afforded by CUR nanoparticles. Buccal film delivery of drug nanoparticles, nevertheless, has been limited to low drug payload. Herein, we evaluated the feasibilities of three mucoadhesive polysaccharides, i.e., hydroxypropyl methylcellulose (HPMC), starch, and hydroxypropyl starch as buccal films of amorphous CUR–chitosan nanoplex at high CUR payload. Both HPMC and starch films could accommodate high CUR payload without adverse effects on the films’ characteristics. Starch films exhibited far superior CUR release profiles at high CUR payload as the faster disintegration time of starch films lowered the precipitation propensity of the highly supersaturated CUR concentration generated by the nanoplex. Compared to unmodified starch, hydroxypropyl starch films exhibited superior CUR release, with sustained release of nearly 100% of the CUR payload in 4 h. Hydroxypropyl starch films also exhibited good payload uniformity, minimal weight/thickness variations, high folding endurance, and good long-term storage stability. The present results established hydroxypropyl starch as the suitable mucoadhesive polysaccharide for high-payload buccal film applications.