Non-ionic Surfactant Vesicles Research Articles

Non-ionic surfactant vesicles exert anti-inflammatory effects through inhibition of NFκB

Inflammation can be an unwanted consequence or cause of debilitating diseases of infectious and non-infectious aetiologies. Current anti-inflammatory medications have several deficiencies including lack of specificity and undesirable side effects. Herein, the potential of non-ionic surfactant vesicles (NISV) comprised of monopalmityol glycerol, dicetyl phosphate and cholesterol) as an anti-inflammatory drug and their mode of action is investigated. NISV were able to inhibit LPS-induced IL-6 from BMD macrophages. The individual components of NISV, monopalmityol glycerol, dicetyl phosphate and cholesterol did not affect LPS induced IL-6 levels, proving that formulation of NISV is essential for their anti-inflammatory effects. Transcriptomic analyses showed NISV mediated down-regulation of transcripts for inflammatory mediators in LPS stimulated macrophages. Notably, NISV downregulate NF-κB transcripts in LPS stimulated macrophages. Measurement of inflammatory mediators by cytometric bead array validated a number of transcriptomic findings as NISV were found to inhibit LPS induced IL-6, IL-12, and multiple chemokines. Further investigation demonstrated that NISV inhibited Poly(I:C) or Pam3csk4 induced inflammatory mediators. This indicates that the effects of NISV are distal to both MyD88 and TRIF signalling. Overall, the data generated highlights the potential of NISV as an anti-inflammatory therapeutic.

Niosomes: A promising approach for targeted drug delivery

Niosomes, also known as nonionic surfactant vesicles, are small lamellar structures that are created by combining nonionic surfactants from the alkyl or dialkyl polyglycerol ether category with cholesterol, and then hydrating them in water-based solutions. These are vesicle systems resembling liposomes that can be utilized as carriers for drugs that are both amphiphilic and lipophilic. The production process of niosomes is derived from liposome technology. The fundamental manufacturing method remains unchanged, wherein the lipid phase is hydrated by the aqueous phase. The lipid phase can consist of either a pure surfactant or a combination of surfactant and cholesterol. Niosomes effectively tackle the challenges associated with medication insolubility, instability, inadequate bioavailability, and fast degradation. The amphiphilic character of niosomes, which combines both hydrophilic and lipophilic properties, enhances their capacity to encapsulate medicines that are either hydrophilic or lipophilic. Cholesterol is frequently utilized as one of the ingredients. Preserving the stiffness of the niosome structure. The present article discusses the essential elements of niosomes, including their structural constituents, methods of manufacturing, and their uses in different disorders.

A glance into factors affecting the possible combined entrapment of curcumin and methylene blue into niosomal formulations as a potential anticancer therapy

Niosomes are non-ionic surfactant vesicles that has successfully attracted a great deal of attention over the last few decades. The best ratio between main components is the key to creating the optimum formulations with substantial loading capacity. Therefore, this study investigated formulation factors that could affect the entrapment of two compounds with different solubilities, namely Methylene blue (MB) and curcumin (CUR) as model hydrophilic and hydrophobic compounds, respectively. The aim was to propose an optimum formula to encapsulate both compounds as a potential hybrid anticancer therapy. The factors with potential influence on the entrapment efficiency (EE) included the type of the non-ionic surfactants (Span 60 versus Span 65), cholesterol to surfactant ratio, and the concentrations of the co-surfactant (Cremophor RH40). Niosomes were prepared by thin film hydration technique and downsized using probe sonicator. The morphology, vesicle size and polydispersity index (PDI) of the prepared vesicles were inspected. The data showed the superiority of Span 65 over Span 60 in terms of higher encapsulation efficiency for MB and CUR. The results reflected positive impact of cholesterol and Cremophor RH40 concentration on EE of the two compounds. The optimum composition of Span 65:cholesterol:Ccremophor RH40 was at the mol% ratio of 45:45:10, respectively, with EE of 91.19 % for CUR alone, 51.70 % for MB alone, and 45.32 %/84.40 % for combined MB/CUR loaded formulations. The vesicle size of the formulations after probe sonication, fall into the range of 100–200 nm, ideal for parenteral delivery to the target sites.

Advancement and Characteristics of Non-Ionic Surfactant Vesicles (Niosome) and their Application for Analgesics

Advancement and Characteristics of Non-Ionic Surfactant Vesicles (Niosome) and their Application for Analgesics

Exploring Niosomes: A Comprehensive Review of their Structure, Formulation, and Biomedical Applications

Niosomes are a novel class of non-ionic surfactant vesicles. They have emerged as promising vesicles for the delivery of a diverse range of therapeutic agents. Niosomes are implied for the improvement of stability and solubility of molecules used in pharmaceutical components. The current study delved into the formulation methods, applications, and recent advancements in niosomal technology. They offer various benefits over other drug delivery systems due to their biocompatibility, biodegradability, and versatility. The first section of this study outlined the background, detailed structure, and characteristics of niosomes. Niosomes are quite distinct in their characteristics as they have the ability to encapsulate both hydrophilic and lipophilic drugs. The second section of the current study highlighted various methods employed for niosome preparation, such as film hydration, reverse-phase evaporation, and microfluidic techniques. By modifying the lipid composition and surfactants, specific physicochemical properties, such as size, lamellarity, and surface charge can be achieved.The final section discussed applications of niosomes across pharmaceutical, cosmetic, and biotechnological fields. These include targeted drug delivery, gene delivery, cosmetic ingredient encapsulation, and vaccine adjuvant systems. Additionally, the recent advancements in niosome research have been discussed as well.

A Comprehensive Review on Niosomes as a Tool for Advanced Drug Delivery.

Over the past few decades, advancements in nanocarrier-based therapeutic delivery have been significant, and niosomes research has recently received much interest. The self-assembled nonionic surfactant vesicles lead to the production of niosomes. The most recent nanocarriers, niosomes, are self-assembled vesicles made of nonionic surfactants with or without the proper quantities of cholesterol or other amphiphilic molecules. Because of their durability, low cost of components, largescale production, simple maintenance, and high entrapment efficiency, niosomes are being used more frequently. Additionally, they enhance pharmacokinetics, reduce toxicity, enhance the solubility of poorly water-soluble compounds, & increase bioavailability. One of the most crucial features of niosomes is their controlled release and targeted diffusion, which is utilized for treating cancer, infectious diseases, and other problems. In this review article, we have covered all the fundamental information about niosomes, including preparation techniques, niosomes types, factors influencing their formation, niosomes evaluation, applications, and administration routes, along with recent developments.

Current developments in Niosomes: Brand new extended release- An Introduction to Nonionic Stable Vesicular Systems

Vesicular systems are an innovative way to distribute drugs in a controlled way, improving bioavailability and achieving a longer-lasting therapeutic effect. When non-ionic surfactant vesicles self-assemble, niosomes are formed. The niosome formation is influenced by a number of variables, including the kind of non-ionic surfactant utilized, the preparation technique, the hydration temperature, etc. We have tried to include all the fundamental information about niosomes in this review article, including the different preparation techniques, types of niosomes, Advantages and disadvantages, niosome characterization, applications, and Drug delivery via niosomes. Lastly, the delivery system's limitations and prospects have also been covered.

Formulation, Evaluation, and Characterization of Indapamide Niosomes

Niosomes, also known as nonionic surfactant vesicles, are one of the many carriers used to carry drug molecules to their target sites. They can hold both hydrophilic and hydrophobic medicines. Indapamide is an angiotensin II type 1 receptor (AT1) antagonist medication primarily used to treat high blood pressure. Niosomes containing Indapamide were created utilizing the thin film hydration process with various cholesterol concentrations and nonionic surfactants (span 60). All noisome formulations were assessed for entrapment efficiency, drug content, reproducibility, vesicular diameter, shape and size distribution microphotography, FTIR analysis, and in vitro release experiments. The results indicate that in all of the created niosomal formulations, as the surfactant content increases, the entrapment efficiency also increases. The drug content ranged between 90.06±0.57 and 96.15±0.42, with a low standard deviation. Niosomes range in size from 0.280±0.098µm to 0.299±0.044µm and have a spherical shape. The IR spectrum analysis indicated no interaction between the medication and the formulation ingredients. Membrane diffusion cells were used to study the in vitro dissolution parameters. The results demonstrate that formulation F6 had a better-controlled release action than other formulations, with an 'n' value of 0.917, indicating that the medication was released using zero-order kinetics.

An Overview of Niosomes

In recent times, there has been a significant shift towards developing targeted biological substances for the treatment of infectious diseases and vaccination. Non-ionic surfactant vesicles, known as niosomes, have emerged as a distinctive vesicular structure in contemporary drug delivery methods due to their biological breakdown, compatibility, chemical resistance, cost-effectiveness, ease of manufacturing and preservation, and low toxicity. The progress in nanocarrier technology has garnered attention for its safety and associated advantages, including enhanced therapeutic administration with diverse pharmacological effects, improved targeting capabilities, and reduced side effects. Niosomes serve as vesicular carriers for drugs, composed of non-ionized surfactants, cholesterol or analogs, and charged molecules that enable controlled and targeted drug delivery. They are categorized as unilamellar, oligolamellar, or multilamellar structures. This comprehensive review article provides an overview of niosomes, covering their structure, types, formulation methods, characterization, advantages and disadvantages, preparation techniques, influencing factors, evaluation criteria, applications, and currently available formulations in the market.
 Keywords: Niosomes, drug delivery system, methods of Preparation, Applications.

Radiolabeling, Characterization, And In Vitro Cell Culture Studies of Donepezil-Loaded Niosome Formulations For Brain Imaging

Dementia has posed a significant public health challenge for aging populations in developed countries for many years. Alzheimer's Disease (AD) is the most prevalent cause of dementia, marked by cognitive and behavioral irregularities resulting from cholinergic dysfunction, a progressive and irreversible neurodegenerative disorder. Restoring cholinergic neurotransmission can alleviate impaired cognitive and behavioral symptoms in AD patients. Donepezil (DNP) is an acetylcholinesterase inhibitor utilized to treat mild to moderate AD symptoms. Niosomes, non-ionic surfactant vesicles, present an array of benefits as drug delivery systems, including stability, non-immunogenicity, permeation potential, and controlled release ability. In this research, we prepared, characterized, radiolabeled with 99mTc, and evaluated DNP-loaded niosome formulations as radiopharmaceuticals for brain imaging agents. The findings suggest that this innovative radiopharmaceutical ([99mTc]Tc-formulation) has the potential to serve as a promising alternative imaging agent for neurological disorders.

Formulation, Evaluation and Characterization of Hydrochlorothiazide Niosomes

One of the many different carriers for getting a drug molecule to its site of action is a niosome, also known as a nonionic surfactant vesicle. Hydrophilic and hydrophobic medicines can both be trapped by them. The primary purpose of the medication hydrochlorothiazide, an angiotensin II type 1 receptor (AT1) antagonist, is to treat high blood pressure. Using cholesterol and nonionic surfactants (span 60) at varying concentrations, niosomes containing hydrochlorothiazide were created by the thin film hydration method. FTIR investigations, in vitro release studies, vesicular diameter, drug content, repeatability, shape and size distribution microphotography, and entrapment efficiency were all assessed for each niosome formulation.According to the findings, entrapment efficiency rises with surfactant concentration in all developed niosomal formulations. Low SD was found for the drug content, which ranged from 90.060.57 to 96.150.42. It was discovered that niosomes ranged in size from 0.280±0.098µm to 0.299±0.044µm and had a spherical shape. The medicine and formulation additives did not interact, according to the IR spectral analysis. Membrane diffusion cells were used to study the in vitro dissolution parameters. The findings indicate that formulation F6 exhibits a more controlled release action compared to the other formulation, with a 'n' value of 0.917, indicating that zero order kinetics were used to release the medication.

Review on Niosome-A Future of Targeted Drug Delivery System

Niosome are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or their lipids. They are vesicular systems similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs. Niosome appears to be a well preferred drug delivery system over liposome as niosome being stable and economic. Also niosomes have great drug delivery potential for targeted delivery of anti-cancer, anti-infective agents. Niosomes can entrap both hydrophilic and lipophilic drugs and can prolong the circulation of the entrapped drug in body. Encapsulation of drug in vesicular system can be predicted to prolong the existence of drug in the systemic circulation and enhance penetration into target tissue, perhaps reduce toxicity if selective uptake can be achieved. This review article focuses on the advantages, disadvantages, preparation methods, factors affecting, characterizations, mechanism of action, and applications of noisome.

C-end rule peptide-guided niosomes for prostate cancer cell targeting

The use of nanoformulations in drug delivery has a significant impact to increase the drug therapeutic efficacy and improve their safety in anticancer treatments. Non-ionic surfactant vesicles (NSVs), or niosomes, are a class of nanocarriers that are low-cost, physiochemical stable, and represent a promising alternative to liposomes. Tumor-penetrating C-end Rule (CendR) peptides, that target neuropilin-1 (NRP-1), a cell surface receptor commonly overexpressed on solid tumor cells, are widely used for precise delivery of diagnostic and therapeutic nanoparticles to malignant lesions. In this study, we investigated the impact of NSV functionalization with prototypic CendR peptide RPARPAR (abbr. RPAR) on NRP-1-dependent targeting of prostate cancer cells. Doxorubicin (DOX)-loaded NSVs, with or without RPAR conjugation, were prepared, physicochemical characterized, and finally tested for NRP-1 binding in human primary prostate carcinoma-1 and prostate carcinoma epithelial cell lines (PPC-1 and 22Rv1, respectively) that are NRP-1 positive, and melanoma (M21) cells that are NRP-1 negative. We demonstrated that the cellular uptake of RPAR-NSVs was NRP-1-dependent and the uptake rate of RPAR-NSVs was ca. ten times higher than un-targeted NSVs in PPC-1 cells; while no significant differences, between targeted and un-targeted nanocarriers, were obtained in M21 cell line. These data were further confirmed by using NRP-1 CendR-binding pocket-blocking (mAb7E8) antibody, which significantly inhibited the internalization of RPAR-NSVs in PPC-1 cells from ca. 80%–3%. The resulting data obtained of cytotoxic studies agreed the uptake results, thus showing a significant increase of cytotoxic effect for RPAR-NSVs@DOX in PPC-1 and 22Rv1 cells compared to NSVs@DOX. These results provide a proof of concept that the conjugation of CendR peptides on the surface of NSVs can increase the specific targeting of nanoparticles in NRP-1 positive cells, thus improving the therapeutic efficacy of resulting targeted nanocarriers for cancer treatment. Our results have important implications for the development of more efficient and selective cancer therapies and support further in vivo studies by using more complex targeting peptides, such as iRGD or other CendR peptides, that are also targeting primary recruitment receptors (i.e. integrins) and are then proteolytically activated into CendR peptides in the tumor microenvironment.

Development and Evaluation of Curcumin-loaded Niosomal Gel for Wound Healing in Rats

Background: The process of wound healing is a complicated series of organized biochemical and cellular phenomena that restore the integrity of the skin and subcutaneous tissue. A drug molecule can be transported to the site of action through a variety of carriers, including niosomes or non-ionic surfactant vesicles. They can trap medications that are both hydrophilic and hydrophobic. It has been demonstrated that curcumin has strong analgesic, anti-inflammatory, and wound-healing qualities. Methods: In the current study, an effort has been made to create a curcumin-loaded niosomal gel for efficient wound healing therapy. Utilizing non-ionic surfactants (Span 60, Span 20, Tween 20, and Tween 60) and cholesterol at various concentrations, a modified thin-film hydration process was used to create niosomal gels containing curcumin. Particle size, shape, entrapment effectiveness, deformability, and in vitro skin penetration were used to describe the vesicles. The 1% carbopol 940 gel was then made using the improved formulation. In wound-induced rats, the effectiveness of the in vivo wound healing was assessed. Results: The manufactured niosomes were discovered to be homogeneous in size and spherical in shape. According to the IR spectrum study, the medication and formulation additives did not interact. It was discovered that the niosomal gel (S-3) loaded with curcumin was not irritating to the skin. According to studies on in vivo wound healing, curcumin-loaded niosomal gel exhibited the highest percentage of wound contraction. Following 21 days of niosomal gel treatment, the histopathological evaluation found a noticeable improvement in the skin's histological architecture. Curcumin-loaded niosomal gel was easily made using the thin film hydration process. Conclusion: The results of this study demonstrate the potential of niosomal gel as a cutting-edge therapeutic strategy for wound healing.

Formulation, optimization and evaluation of amisulpride-loaded niosomal intranasal gel for brain targeting.

Aim: To develop stable non-ionic surfactant vesicles containing amisulpride (AMS) to improve brain uptake via nose to brain mechanism. Methods: Niosomes were developed using a modified ethanol injection technique, optimized using 32 factorial design and evaluated for the vesicle size (VS), percent encapsulation efficiency (EE), zeta potential (ZP) and % cumulative drug release (%CDR). Results: Optimized niosomes (Span-60: cholesterol ratio 0:1) showed 191.4nm VS, 84.25% EE, -38.2ZP and 81.31% CDR. In situ gel with these niosomes displayed 78% CDR. TEM analysis revealed spherical niosomes. Pharmacokinetic and brain tissue distribution studies in rats showed enhanced plasma and brain concentrations, indicating successful brain targeting. Conclusion: This strategy demonstrates improved AMS permeation via the nasal cavity, enhancing bioavailability for treating schizophrenia.

FUS and surfactant-based nanocarriers: A combined strategy for nose to brain drug delivery

Brain drug delivery is hampered by the presence of the blood brain barrier and nanocarriers, administered by intranasal route, could represent an alternative and efficient strategy to improve drug localization in the Central Nervous System (CNS). The aim of this work is to design and characterize non-ionic surfactant vesicles (NSVs) and perfluorocarbon gas non-ionic surfactant based nanobubbles (VNBs) suitable for Nose to Brain Delivery (N2B). In particular, Pluronic F127, Span 85 and cholesterol have been employed to prepare NSVs and VNBs. Both systems have been characterized in terms of (a) hydrodynamic diameter, ζ-potential and morphology (b) vesicle bilayer feature (anisotropy), (c) physical-chemical stability and (d) fluorescent model probe release capability. VNBs have been also studied in terms of gas entrapment and acoustic efficiency. In addition, in order to understand optimal ultrasound (US) parameters to obtain in vitro stable cavitation, the acoustic pressure effect on VNBs fluorescent probes release kinetics was evaluated. The obtained results suggest that NSVs and VNBs show a hydrodynamic diameter suitable for N2B delivery. Moreover, in this study, we develop a new kind of protocol to evaluate an in vitro US characterization of VNBs and our data suggest a stable and controlled probe release, encouraging the possibility to deliver VNBs in mixture with NSVs loaded neuroprotective drugs for brain delivery coupled to US obtaining stable cavitation. In this context, extracellular field recordings in specific area of hippocampus (CA1-CA3) have been carried out in order to assure that empty NSVs do not affect synaptic plasticity in the form of long-term potentiation, a molecular mechanism which underlies learning and memory.

Niosomal Drug Delivery for Oral Route

Abstract: Niosomes are artificial vesicles with potential technological advantages. They are non-ionic surfactant vesicles. As efficient drug delivery systems with a wide range of uses, niosomes have the same potential benefits as phospholipid vesicles (liposomes), including the capacity to hold both water- and lipid-soluble pharmaceutical molecules. Niosomes can also be thought of as more cost-effective, chemically stable, and occasionally physically stable alternatives to liposomes. Simple preparation techniques and commonly used surfactants in pharmaceutical technology can be employed to create niosomes. Numerous studies have covered noisome physicochemical characteristics and their uses as drug delivery vehicles. In this report, a brief and simplified summary of different theories of self-assembly are discussed. Furthermore, manufacturing methods, physical characterization techniques, bilayer membrane additives, unconventional niosomes (discomes, proniosomes, elastic and polyhedral niosomes), their recent applications as drug delivery systems, limitations and directions for future research will be discussed.

Preparation and Evaluation of Niosomal Transdermal Patch of Clozapine

Niosomes are the non-ionic surfactant vesicles obtained on hydration of synthetic non-ionic surfactants. These are the promising vehicles for effective transdermal drug delivery. The present research work was aimed to develop niosomal-based transdermal Clozapine patch containing a stable formulation with improved drug permeation. Niosomes were prepared by solvent casting method. All the formulations were evaluated for vesicle size, zeta potential and percent entrapment efficiency. All the patches were then characterized for thickness, folding endurance, drug content determination, Flatness, and in vitro permeation studies. F3 formulation having optimum vesicle size (2.6m), highest zeta potential (-32.56mV) and maximum percent entrapment efficiency (98.09%) was selected as optimized formulation. The transdermal patch was prepared using solvent casting method from the optimised niosomes formulation F3 formulation. The prepared optimised niosomes F3 formulation were loaded into the patch formulation. Patches loaded with niosomes (F3NT3) showed 95.78 % cumulative amount of drug permeated. The optimized formulation (F3NT3) followed first order release kinetics.

Construction of pH and Temperature Dual-Responsive Ceramide Delivery System in the Stratum Corneum

Ceramides are major components within the intercellular lamella of the stratum corneum and play an important role in the barrier function of skin. Thus, cosmetic products containing ceramides are expected to maintain and improve the skin barrier. However, maintaining the stability of ceramides within cosmetic products remains a challenge owing to their high crystallinity. Our previous study demonstrated a promising method for the incorporation of ceramides into a lotion via complexation with nonionic surfactant vesicles (i.e., niosomes). However, the stable complexation of ceramides within niosomes may interfere with their beneficial properties, because ceramides improve the skin barrier via lamella formation. Consequently, the skin moisturizing effect of the ceramide-complexed niosomes (CCNs) was insufficient. Thus, it was hypothesized that the properties of ceramide could be maximized by encouraging the collapse of the CCNs upon contact with the stratum corneum. The destabilization of nanoparticles is often achieved using stimuli-responsive polymers, which change their hydrophobicity depending on the external environment and disrupt the nanoparticle structure through hydrophobic interaction. A range of pH and temperature dual-responsive polymers (poly(MD-MAA-LT)s) was been developed in our previous study, and is responsive to the slightly acidic pH and moderately high temperature of human skin. In this study, we construct pH and temperature dual-responsive CCNs (Res-CCNs) through the modification of the CCNs with poly (MD-MAA-LT) s. The Res-CCNs were stable throughout a wide temperature range of 5 to 50°C when held at a constant pH of 6.5. However, the size of Res-CCNs increased significantly when the temperature was increased under the slightly more acidic conditions of human skin (pH of 5.0), which led to the release of ceramide. In addition, Res-CCNs showed a moisturizing effect for an extended period, when applied on human skin. This novel approach to the application of ceramides is expected to promote the benefits of ceramides in the skin care field.

Nanovesicles as Vanillin Carriers for Antimicrobial Applications.

Vanillin is a natural compound easily extracted from plants. It has neuroprotective, anti-carcinogenic, antioxidant, antimicrobial, and anti-biofilm properties. It also presents high volatility, high hydrophilicity, and low bioavailability. Nanomaterials can be used to improve pharmacodynamics, solubility, and stability and to enhance pharmacokinetics. In this work, non-ionic surfactant vesicles were synthesized as vanillin carriers: neutral niosomes formed by Span60 and cholesterol, positive charged niosomes formulated with cetyltrimethylammonium bromide (CTAB), and negatively charged niosomes formulated with sodium dodecyl sulfate (SDS). Niosomes synthesis was carried out with two commonly used methods: thin film hydration (TFH) and ethanol injection method (EIM). The niosomes synthesized were used to prepare two different materials: (i) a powder containing the lyophilized noisome with vanillin systems and (ii) a gelatin matrix film containing niosomes with vanillin. Lyophilization was carried out using maltodextrin as a cryoprotectant. The lyophilization of colloidal structures allows for storage at room temperature for long periods of time, keeping their organoleptic characteristics invariable. Niosomes were characterized before and after the lyophilization process in terms of morphological characterization, size, polydispersity index (PDI), and zeta potential. Moreover, niosomes cargo was evaluated by calculating the encapsulation efficiency (EE) and loading capacity (LC). Results showed that the use of the TFH method allowed us to obtain niosomes of 255 nm with high EE (up to 40%) and LC values higher than EIM. The lyophilization process decreased the LC of the vesicles prepared, but this decrease was mitigated by up to 20% when ionic surfactants were used on the membrane bilayer. Gelatin films are biodegradable materials suitable for food packing applications. The incorporation of a natural compound with antimicrobial activity would be a clear advantage for such an application. The films prepared were characterized in terms of morphology, water solubility, color, and transparency. Niosomes synthesized by thin film hydration had better chemical and physical properties to load vanillin. Especially in the case of application in films, niosomes with a negative charge, formed by SDS, and vanillin loaded gave better mechanical and chemical characteristics to the film.