Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine.

DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection. In this study, we have engineered a range of polymer-based nanocarriers based on the poly(beta-amino ester) (PBAE) polycation platform to investigate the role that surface poly(ethylene glycol) (PEG) density has on pDNA encapsulation, formulation properties and gene transfectability both in vitro and in vivo. We achieved this by synthesising a non-PEGylated and PEGylated PBAE and produced formulations containing these PBAEs, and mixed polyplexes to tune surface PEG density. All polymers and co-formulations produced small polyplex nanoparticles with almost complete encapsulation of the cargo in all cases. Despite high gene transfection in HEK293T cells, only the fully PEGylated and mixed formulations displayed significantly higher expression of the reporter gene than the negative control in dendritic cells. Further in vivo studies with a bivalent SARS-CoV-2 pDNA vaccine revealed that only the mixed formulation led to strong antigen specific T-cell responses, however this did not translate into the presence of serum antibodies indicating the need for further studies into improving immunisation with polymer delivery systems.

Multiple drug-delivery strategies to enhance the pharmacological and toxicological properties of Mefenamic acid.

OBJECTIVE: To improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS). METHODS: The in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer. RESULTS: When the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS. CONCLUSIONS: These preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs.

Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models.

Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we performed in vitro screening of combinations of these drugs, administered directly or encapsulated within polymer nanoparticles, in both 2D and in 3D spheroid models of breast cancer. A variety of assays were used to evaluate drug potency, and calculations of combination index (CI) values indicated that synergistic effects of drug combinations occurred in a molar-ratio dependent manner. It is suggested that the mechanisms of synergy were related to enhancement of DNA damage as shown by the level of double-strand DNA breaks, and mechanisms of antagonism associated with mitochondrial mediated cell survival, as indicated by reactive oxygen species (ROS) generation. Enhanced drug delivery and potency was observed with nanoparticle formulations, with a greater extent of doxorubicin localised to cell nuclei as evidenced by microscopy, and higher cytotoxicity at the same time points compared to free drugs. Together, the work presented identifies specific combinations of doxorubicin and olaparib which were most effective in a panel of TNBC cell lines, explores the mechanisms by which these combined agents might act, and shows that formulation of these drug combinations into polymeric nanoparticles at specific ratios conserves synergistic action and enhanced potency in vitro compared to the free drugs.

Glycerol-based sustainably sourced resin for volumetric printing.

Volumetric Additive Manufacturing (VAM) represents a revolutionary advancement in the field of Additive Manufacturing, as it allows for the creation of objects in a single, cohesive process, rather than in a layer-by-layer approach. This innovative technique offers unparalleled design freedom and significantly reduces printing times. A current limitation of VAM is the availability of suitable resins with the required photoreactive chemistry and from sustainable sources. To support the application of this technology, we have developed a sustainable resin based on polyglycerol, a bioderived (e.g., vegetable origin), colourless, and easily functionisable oligomer produced from glycerol. To transform polyglycerol-6 into an acrylate photo-printable resin we adopted a simple, one-step, and scalable synthesis route. Polyglycerol-6-acrylate fulfils all the necessary criteria for volumetric printing (transparency, photo-reactivity, viscosity) and was successfully used to print a variety of models with intricate geometries and good resolution. The waste resin was found to be reusable with minimal performance issues, improving resin utilisation and minimising waste material. Furthermore, by incorporating dopants such as poly(glycerol) adipate acrylate (PGA-A) and 10,12-pentacosadyinoic acid (PCDA), we demonstrated the ability to print objects with a diverse range of functionalities, including temperature sensing probes and a polyester excipient, highlighting the potential applications of these new resins.

Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers.

The therapeutic efficacy of nanomedicines is highly dependent on their access to target sites in the body, and this in turn is markedly affected by their size, shape and transport properties in tissue. Although there have been many studies in this area, the ability to design nanomaterials with optimal physicochemical properties for in vivo efficacy remains a significant challenge. In particular, it is often difficult to quantify the detailed effects of cancer drug delivery systems in vivo as tumour volume reduction, a commonly reported marker of efficacy, does not always correlate with cytotoxicity in tumour tissue. Here, we studied the behaviour in vivo of two specific poly(2-hydroxypropyl methacrylamide) (pHPMA) pro-drugs, with hyperbranched and chain-extended branched architectures, redox-responsive backbone components, and pH-sensitive linkers to the anti-cancer drug doxorubicin. Evaluation of the biodistribution of these polymers following systemic injection indicated differences in the circulation time and organ distribution of the two polymers, despite their very similar hydrodynamic radii (∼10 and 15 nm) and architectures. In addition, both polymers showed improved tumour accumulation in orthotopic triple-negative breast cancers in mice, and decreased accumulation in healthy tissue, as compared to free doxorubicin, even though neither polymer-doxorubicin pro-drug decreased overall tumour volume as much as the free drug under the dosing regimens selected. However, the results of histopathological examinations by haematoxylin and eosin, and TUNEL staining indicated a higher population of apoptotic cells in the tumours for both polymer pro-drug treatments, and in turn a lower population of apoptotic cells in the heart, liver and spleen, as compared to free doxorubicin treatment. These data suggest that the penetration of these polymer pro-drugs was enhanced in tumour tissue relative to free doxorubicin, and that the combination of size, architecture, bioresponsive backbone and drug linker degradation yielded greater efficacy for the polymers as measured by biomarkers than that of tumour volume. We suggest therefore that the effects of nanomedicines may be different at various length scales relative to small molecule free drugs, and that penetration into tumour tissue for some nanomedicines may not be as problematic as prior reports have suggested. Furthermore, the data indicate that dual-responsive crosslinked polymer-prodrugs in this study may be effective nanomedicines for breast cancer chemotherapy, and that endpoints beyond tumour volume reduction can be valuable in selecting candidates for pre-clinical trials.

Poly (diglycerol adipate) variants as enhanced nanocarrier replacements in drug delivery applications.

Sustainably derived poly(glycerol adipate) (PGA) has been deemed to deliver all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability. To overcome this, in the present work, we applied a more significant variation of the polyester backbone while maintaining mild and sustainable polymerisation conditions. We have investigated the effect of the variation of both hydrophilic and hydrophobic segments upon physical properties and drug interactions as well as self-assembly and NPs stability. For the first time we have replaced glycerol with the more hydrophilic diglycerol, as well as adjusting the final amphiphilic balance of the polyester repetitive units by incorporating the more hydrophobic 1,6-n-hexanediol (Hex). The properties of the novel poly(diglycerol adipate) (PDGA) variants have been compared against known polyglycerol-based polyesters. Interestingly, while the bare PDGA showed improved water solubility and diminished self-assembling ability, the Hex variation demonstrated enhanced features as a nanocarrier. In this regard, PDGAHex NPs were tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo (whole organism) experiments.

Long-circulating magnetoliposomes as surrogates for assessing pancreatic tumour permeability and nanoparticle deposition.

Nanocarriers are candidates for cancer chemotherapy delivery, with growing numbers of clinically-approved nano-liposomal formulations such as Doxil® and Onivyde® (liposomal doxorubicin and irinotecan) providing proof-of-concept. However, their complex biodistribution and the varying susceptibility of individual patient tumours to nanoparticle deposition remains a clinical challenge. Here we describe the preparation, characterisation, and biological evaluation of phospholipidic structures containing solid magnetic cores (SMLs) as an MRI-trackable surrogate that could aid in the clinical development and deployment of nano-liposomal formulations. Through the sequential assembly of size-defined iron oxide nanoparticle clusters with a stabilizing anionic phospholipid inner monolayer and an outer monolayer of independently-selectable composition, SMLs can mimic physiologically a wide range of nano-liposomal carrier compositions. In patient-derived xenograft models of pancreatic adenocarcinoma, similar tumour deposition of SML and their nano-liposomal counterparts of identical bilayer composition was observed in vivo, both at the tissue level (fluorescence intensities of 1.5 × 108 ± 1.8 × 107 and 1.2 × 108 ± 6.3 × 107, respectively; ns, 99% confidence interval) and non-invasively using MR imaging. We observed superior capabilities of SML as a surrogate for nano-liposomal formulations as compared to other clinically-approved iron oxide nano-formulations (ferumoxytol). In combination with diagnostic and therapeutic imaging tools, SMLs have high clinical translational potential to predict nano-liposomal drug carrier deposition and could assist in stratifying patients into treatment regimens that promote optimal tumour deposition of nanoparticulate chemotherapy carriers. STATEMENT OF SIGNIFICANCE: Solid magnetoliposomes (SMLs) with compositions resembling that of FDA-approved agents such as Doxil® and Onivyde® offer potential application as non-invasive MRI stratification agents to assess extent of tumour deposition of nano-liposomal therapeutics prior to administration. In animals with pancreatic adenocarcinoma (PDAC), SML-PEG exhibited (i) tumour deposition comparable to liposomes of the same composition; (ii) extended circulation times, with continued tumour deposition up to 24 hours post-injection; and (iii) MRI capabilities to determine tumour deposition up to 1 week post-injection, and confirmation of patient-to-patient variation in nanoparticulate deposition in tumours. Hence SMLs with controlled formulation are a step towards non-invasive MRI stratification approaches for patients, enabled by evaluation of the extent of deposition in tumours prior to administration of nano-liposomal therapeutics.

A holistic NMR framework to understand environmental impact: Examining the impacts of superparamagnetic iron oxide nanoparticles (SPIONs) in Daphnia magna via imaging, spectroscopy, and metabolomics.

Superparamagnetic iron oxide nanoparticles (SPIONs) are a contaminant of emerging interest, often used in the medical field as an imaging contrast agent, with additional uses in wastewater treatment and as food additives. Although the use of SPIONs is increasing, little research has been conducted on the toxic impacts to living organisms beyond traditional lethal concentration endpoints. Daphnia magna are model organisms for aquatic toxicity testing with a well understood metabolome and high sensitivity to SPIONs. Thus, as environmental concentrations continue to increase, it is becoming critical to understand their sub-lethal toxicity. Due to the paramagnetic nature of SPIONs, a range of potential nuclear magnetic resonance spectroscopy (NMR) experiments are possible, offering the potential to probe the physical location (via imaging), binding (via relaxation weighted spectroscopy), and the biochemical pathways impacted (via in vivo metabolomics). Results indicate binding to carbohydrates, likely chitin in the exoskeleton, along with a decrease in energy metabolites and specific biomarkers of oxidative stress. The holistic NMR framework used here helps provide a more comprehensive understanding of SPIONs impacts on D. magna and showcases NMR's versatility in providing physical, chemical, and biochemical insights.

Hybrid Poly(ß-amino ester) Triblock Copolymers Utilizing a RAFT Polymerization Grafting-From Methodology.

The biocompatibility, biodegradability, and responsiveness of poly(ß-amino esters) (PBAEs) has led to their widespread use as biomaterials for drug and gene delivery. Nonetheless, the step-growth polymerization mechanism that yields PBAEs limits the scope for their structural optimization toward specific applications because of limited monomer choice and end-group modifications. Moreover, to date the post-synthetic functionalization of PBAEs has relied on grafting-to approaches, challenged by the need for efficient polymer-polymer coupling and potentially difficult post-conjugation purification. Here a novel grafting-from approach to grow reversible addition-fragmentation chain transfer (RAFT) polymers from a PBAE scaffold is described. This is achieved through PBAE conversion into a macromolecular chain transfer agent through a multistep capping procedure, followed by RAFT polymerization with a range of monomers to produce PBAE-RAFT hybrid triblock copolymers. Following successful synthesis, the potential biological applications of these ABA triblock copolymers are illustrated through assembly into polymeric micelles and encapsulation of a model hydrophobic drug, followed by successful nanoparticle (NP) uptake in breast cancer cells. The findings demonstrate this novel synthetic methodology can expand the scope of PBAEs as biomaterials.

N-Hydroxyethyl acrylamide as a functional eROP initiator for the preparation of nanoparticles under "greener" reaction conditions.

N-Hydroxyethyl acrylamide was used as a functional initiator for the enzymatic ring-opening polymerisation of ε-caprolactone and δ-valerolactone. N-Hydroxyethyl acrylamide was found not to undergo self-reaction in the presence of Lipase B from Candida antarctica under the reaction conditions employed. By contrast, this is a major problem for 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate which both show significant transesterification issues leading to unwanted branching and cross-linking. Surprisingly, N-hydroxyethyl acrylamide did not react fully during enzymatic ring-opening polymerisation. Computational docking studies helped us understand that the initiated polymer chains have a higher affinity for the enzyme active site than the initiator alone, leading to polymer propagation proceeding at a faster rate than polymer initiation leading to incomplete initiator consumption. Hydroxyl end group fidelity was confirmed by organocatalytic chain extension with lactide. N-Hydroxyethyl acrylamide initiated polycaprolactones were free-radical copolymerised with PEGMA to produce a small set of amphiphilic copolymers. The amphiphilic polymers were shown to self-assemble into nanoparticles, and to display low cytotoxicity in 2D in vitro experiments. To increase the green credentials of the synthetic strategies, all reactions were carried out in 2-methyl tetrahydrofuran, a solvent derived from renewable resources and an alternative for the more traditionally used fossil-based solvents tetrahydrofuran, dichloromethane, and toluene.

Formation of hydrated PEG layers on magnetic iron oxide nanoflowers shows internal magnetisation dynamics and generates high in-vivo efficacy for MRI and magnetic hyperthermia.

Multicore magnetic iron oxide nanoparticles, nanoflowers (NFs), have potential biomedical applications as efficient mediators for AC-magnetic field hyperthermia and as contrast agents for magnetic resonance imaging due to their strong magnetic responses arising from complex internal magnetic ordering. To realise these applications amenable surface chemistry must be engineered that maintain particle dispersion. Here a catechol-derived grafting approach is described to strongly bind polyethylene glycol (PEG) to NFs and provide stable hydrogen-bonded hydrated layers that ensure good long-term colloidal stability in buffers and media even at clinical MRI field strength and high concentration. The approach enables the first comprehensive study into the MRI (relaxivity) and hyperthermic (SAR) efficiencies of fully dispersed NFs. The predominant role of internal magnetisation dynamics in providing high relaxivity and SAR is confirmed, and it is shown that these properties are unaffected by PEG molecular weight or corona formation in biological environments. This result is in contrast to traditional single core nanoparticles which have significantly reduced SAR and relaxivity upon PEGylation and on corona formation, attributed to reduced Brownian contributions and weaker NP solvent interactions. The PEGylated NF suspensions described here exhibit usable blood circulation times and promising retention of relaxivity in-vivo due to the strongly anchored PEG layer. This approach to biomaterials design addresses the challenge of maintaining magnetic efficiency of magnetic nanoparticles in-vivo for applications as theragnostic agents. STATEMENT OF SIGNIFICANCE: Application of multicore magnetic iron-oxide nanoflowers (NFs) as efficient mediators for AC-field hyperthermia and as contrast agents for MR imaging has been limited by lack of colloidal stability in complex media and biosystems. The optimized materials design presented is shown to reproducibly provide PEG grafted NF suspensions of exceptional colloidal stability in buffers and complex media, with significant hyperthermic and MRI utility which is unaffected by PEG length, anchoring group or bio-molecular adsorption. Deposition in the selected pancreatic tumour model mirrors liposomal formulations providing a quantifiable probe of tissue-level liposome deposition and relaxivity is retained in the tumour microenvironment. Hence the biomaterials design addresses the longstanding challenges of maintaining the in vivo magnetic efficiency of nanoparticles as theragnostic agents.

Oxygen-Tolerant RAFT Polymerization Initiated by Living Bacteria.

Living organisms can synthesize a wide range of macromolecules from a small set of natural building blocks, yet there is potential for even greater materials diversity by exploiting biochemical processes to convert unnatural feedstocks into new abiotic polymers. Ultimately, the synthesis of these polymers in situ might aid the coupling of organisms with synthetic matrices, and the generation of biohybrids or engineered living materials. The key step in biohybrid materials preparation is to harness the relevant biological pathways to produce synthetic polymers with predictable molar masses and defined architectures under ambient conditions. Accordingly, we report an aqueous, oxygen-tolerant RAFT polymerization platform based on a modified Fenton reaction, which is initiated by Cupriavidus metallidurans CH34, a bacterial species with iron-reducing capabilities. We show the synthesis of a range of water-soluble polymers under normoxic conditions, with control over the molar mass distribution, and also the production of block copolymer nanoparticles via polymerization-induced self-assembly. Finally, we highlight the benefits of using a bacterial initiation system by recycling the cells for multiple polymerizations. Overall, our method represents a highly versatile approach to producing well-defined polymeric materials within a hybrid natural-synthetic polymerization platform and in engineered living materials with properties beyond those of biotic macromolecules.

Graphene oxide modulates inter-particle interactions in 3D printable soft nanocomposite hydrogels restoring magnetic hyperthermia responses.

Hydrogels loaded with magnetic iron oxide nanoparticles that can be patterned and which controllably induce hyperthermic responses on AC-field stimulation are of interest as functional components of next-generation biomaterials. Formation of nanocomposite hydrogels is known to eliminate any Brownian contribution to hyperthermic response (reducing stimulated heating) while the Néel contribution can also be suppressed by inter-particle dipolar interactions arising from aggregation induced before or during gelation. We describe the ability of graphene oxide (GO) flakes to restore the hyperthermic efficiency of soft printable hydrogels formed using Pluronics F127 and PEGylated magnetic nanoflowers. Here, by varying the amount of GO in mixed nanocomposite suspensions and gels, we demonstrate GO-content dependent recovery of hyperthemic response in gels. This is due to progressively reduced inter-nanoflower interactions mediated by GO, which largely restore the dispersed-state Néel contribution to heating. We suggest that preferential association of GO with the hydrophobic F127 blocks increases the preponderance of cohesive interactions between the hydrophilic blocks and the PEGylated nanoflowers, promoting dispersion of the latter. Finally we demonstrate extrusion-based 3D printing with excellent print fidelity of the magnetically-responsive nanocomposites, for which the inclusion of GO provides significant improvement in the spatially-localized open-coil heating response, rendering the prints viable components for future cell stimulation and delivery applications.

Polymer Pro-Drug Nanoparticles for Sustained Release of Cytotoxic Drugs Evaluated in Patient-Derived Glioblastoma Cell Lines and In Situ Gelling Formulations.

Glioblastoma (GBM) is the most common, malignant and aggressive brain tumour in adults. Despite the use of multimodal treatments, involving surgery, followed by concomitant radiotherapy and chemotherapy, the median survival for patients remains less than 15 months from diagnosis. Low penetration of drugs across the blood-brain barrier (BBB) is a dose-limiting factor for systemic GBM therapies, and as a result, post-surgical intracranial drug delivery strategies are being developed to ensure local delivery of drugs within the brain. Here we describe the effects of PEGylated poly(lactide)-poly(carbonate)-doxorubicin (DOX) nanoparticles (NPs) on the metabolic activity of primary cancer cell lines derived from adult patients following neurosurgical resection, and the commercially available GBM cell line, U87. The results showed that non-drug-loaded NPs were well tolerated at concentrations of up to 100 µg/mL while tumour cell-killing effects were observed for the DOX-NPs at the same concentrations. Further experiments evaluated the release of DOX from polymer-DOX conjugate NPs when incorporated in a thermosensitive in situ gelling poly(DL-lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) matrix paste, in order to simulate the clinical setting of a locally injected formulation for GBM following surgical tumour resection. These assays demonstrated drug release from the polymer pro-drugs, when in PLGA/PEG matrices of two formulations, over clinically relevant time scales. These findings encourage future in vivo assessment of the potential capability of polymer-drug conjugate NPs to penetrate brain parenchyma efficaciously, when released from existing interstitial delivery systems.

Enhanced Stability and Emission Properties of Perylene Dyes by Surface Tethering: Preparation of Fluorescent Ru Nanoparticle Suspensions by Alkyne Linker Chemistry.

Spherical ruthenium nanoparticles (NPs) with a narrow size distribution were synthesised in ethanol by a facile low-temperature solvothermal process without the assistance of templates, structure-directing agents or post annealing/reduction treatments. Surface passivation with a fluorescent perylene dye (EP), and with silane ligands (ETMS), both initially bearing alkyne groups and subsequently forming vinylidene linkages, provided stable suspensions of the marginally soluble free EP. Quantitative analysis of the suspension gave an estimated EP surface coverage of 15 %, corresponding to an EP/ETMS mole ratio of ≈1:6. Photophysical evaluation of the bound and free dye revealed similar absorption bands and extinction coefficients and improved properties for the bound state, including enhanced fluorescence in the visible range for the bound dye, an extended absorption range into the near-UV providing strong emission in the visible, and significantly improved photostability. The physical basis of the enhanced photophysical properties, potential routes to further improvements and the implications for applications are discussed.

Photoswitchable Layer-by-Layer Coatings Based on Photochromic Polynorbornenes Bearing Spiropyran Side Groups.

Herein, we present the synthesis of linear photochromic norbornene polymers bearing spiropyran side groups (poly(SP-R)) and their assembly into layer-by-layer (LbL) films on glass substrates when converted to poly(MC-R) under UV irradiation. The LbL films were composed of bilayers of poly(allylamine hydrochloride) (PAH) and poly(MC-R), forming (PAH/poly(MC-R)) n coatings. The merocyanine (MC) form presents a significant absorption band in the visible spectral region, which allowed tracking of the LbL deposition process by UV-vis spectroscopy, which showed a linear increase of the characteristic MC absorbance band with increasing number of bilayers. The thickness and morphology of the (PAH/poly(MC-R)) n films were characterized by ellipsometry and scanning electron microscopy, respectively, with a height of ∼27.5 nm for the first bilayer and an overall height of ∼165 nm for the (PAH/poly(MC-R))5 multilayer film. Prolonged white light irradiation (22 h) resulted in a gradual decrease of the MC band by 90.4 ± 2.9% relative to the baseline, indicating the potential application of these films as coatings for photocontrolled delivery systems.