Controlled Drug Delivery Applications Research Articles

A Brief Study on Nanogel: A Review

Strong nanoparticles called nanogels may be utilized in controlled drug delivery applications to distribute active pharmaceutical ingredients. Because of their chemical makeup and formulations that are unsuited for other formulations, nanogels provide a safer and more effective drug delivery mechanism for both hydrophilic and hydrophobic medicines. Functionalized nanoparticles, which serve as drug carriers and can be loaded with medications and other active materials to be released in a regulated way at a specific spot, can now be larger thanks to nanogel technology. The objective of this paper is to present a broad overview of nanogels, their innovative applications across several domains, and their latest synthesis process.

Stimuli-responsive azo-functionalized non-ionic amphiphiles for controlled drug delivery applications

A series of stimuli-responsive non-ionic amphiphiles have been synthesized consisting of n-alkyl/fluoroalkyl chain to impart lipophilicity, and lactose/polyethylene glycol units which confers hydrophilicity. To execute the release of encapsulated guest in a controlled manner, the azo and ester functionalities were incorporated in the synthesized amphiphiles. The ability of the azo unit to undergo trans–cis-trans spatiotemporal isomerization under UV irradiation with subsequent release of the encapsulated guest has been studied in the aqueous solution of amphiphiles at 365 and 254 nm. Furthermore, an immobilized enzyme Candida antarctica lipase (Novozym 435), a hydrolase, was observed to facilitate the cleavage of the ester moiety of the synthesized amphiphiles resulting in the gradual collapse of the nano-aggregates and subsequent release of encapsulated guest. The aggregation and guest encapsulation behaviour of synthesized azo-functionalized amphiphiles were studied by dynamic light scattering (DLS), critical micelle concentration (CMC), and transmission electron microscopy, fluorescence and UV–Vis spectroscopy. Entrapment of hydrophobic drug/dye i.e. curcumin/Nile red in the lipophilic core, their cellular uptake, and consequently the stimuli responsive release of payload demonstrated the potential of these nanostructures in controlled drug delivery applications.

Liposome-Hydrogel Composites for Controlled Drug Delivery Applications.

Various controlled delivery systems (CDSs) have been developed to overcome the shortcomings of traditional drug formulations (tablets, capsules, syrups, ointments, etc.). Among innovative CDSs, hydrogels and liposomes have shown great promise for clinical applications thanks to their cost-effectiveness, well-known chemistry and synthetic feasibility, biodegradability, biocompatibility and responsiveness to external stimuli. To date, several liposomal- and hydrogel-based products have been approved to treat cancer, as well as fungal and viral infections, hence the integration of liposomes into hydrogels has attracted increasing attention because of the benefit from both of them into a single platform, resulting in a multifunctional drug formulation, which is essential to develop efficient CDSs. This short review aims to present an updated report on the advancements of liposome-hydrogel systems for drug delivery purposes.

Preparation And Characterization of Polyvinyl Alcohol Nanofiber Loaded With Mafenide For Sustain Release

This paper delves into the intricate process of preparing and characterizing Polyvinyl alcohol (PVA) nanofibers loaded with Mafenide to achieve sustained release functionality. The synthesis involves the careful integration of Mafenide, a pharmaceutical agent known for its antimicrobial properties, into PVA nanofibers. This combination holds promise for controlled drug delivery applications. The preparation begins with the electrospinning technique, a method widely employed for creating nanofibrous structures. During this process, the Mafenide is incorporated into the PVA matrix, forming a composite material. The choice of Polyvinyl alcohol as the base material is strategic, given its biocompatibility and excellent film-forming properties. The characterization phase involves a comprehensive analysis of the resulting nanofibers. Techniques such as scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR). are employed to examine the morphology and chemical composition of the nanofibrous system. These analyses provide insights into the structural integrity and the successful incorporation of Mafenide. The study focuses on the sustained release aspect, aiming to understand how the loaded Mafenide interacts within the PVA nanofibers over time. This sustained release mechanism is crucial for pharmaceutical applications, offering prolonged therapeutic effects and minimizing the need for frequent administration. The potential benefits of this research lie in the development of an efficient drug delivery system.

Pivalic acid based N-doped carbon dots for drug delivery and antioxidant behaviour

Heteroatom doped surface engineered carbon dots has immense potential not only in their fluorescent sensing but also in nanocarrier for drug molecules and antioxidant behavior. Herein, we report a one-step thermal coupling synthesis of carbon dots from pivalic acid and naturally abundant gelatin (PGCDs). The as-synthesized PGCDs exhibited excellent colloidal stability, biocompatibility, and antioxidant activity. The surface of PGCDs was further modified with anticancer drug molecules to assess their drug delivery capabilities. The drug-loaded PGCDs demonstrated sustained release profiles, indicating their potential for controlled drug delivery applications. For understanding the drug delivery mechanism, the cumulative release data have been fitted into Weibull and Higuchi model. The PGCDs also showed pH sensitive release behavior where acidic environment has a better control in release profile compared to the alkaline pH. The concentration dependent radical activity shows more than 80% activity at below 1 mg/mL PGCDs concentration. Their low toxicity against live human cell lines could promote this PGCDs as a potential versatile nano-vector biomedical research area.

Advanced 3D Electrospinning "Xspin" System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery.

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.

Chitosan based hybrid superabsorbent for controlled drug delivery application.

In the present study, a hybrid chitosan-alginate superabsorbent is prepared using maleic acid as a cross-linker and acrylamide as a grafting agent using the free radical mechanism. The composite hydrogel shows good swelling capacity along with hemocompatibility and biocompatibility and hence it is utilized as a drug delivery device. The characterization techniques including x-ray diffraction, Fourier transform infrared, x-ray photoelectron spectroscopy, and thermal analysis indicate the successful synthesis of stable hydrogel with rich functionalities. Metformin hydrochloride is used as a model drug which is used to treat diabetes. The drug encapsulation is done using the swelling diffusion method after the synthesis of hydrogel. The release of metformin from the drug-loaded hydrogel at physiological pH highlights the role of non-covalent interactions between the drug and hydrogel. In vitro release studies of Metformin from the drug-loaded hydrogel show higher release profiles at intestinal pH (7.4) compared to stomach pH (1.2). The observed cumulative release is 82.71% at pH 7.4 and 45.67% at pH 1.2 after 10 h. Brunauer-Emmett-Teller analysis reveals the effect of surface area, pore size, and pore volume of hydrogel on the drug release. The drug release from the hybrid chitosan-alginate hydrogel is found to be more sustained in comparison to the pure chitosan hydrogel. For the present drug delivery system, the swelling-controlled release is found to be more dominating than the pH-controlled release. The synthesized hydrogel can be successfully employed as a potential drug delivery system for controlled drug delivery.

Poly(lactic acid): Synthesis, modification and applications in controlled drug delivery

Poly(lactic acid) (PLA) is the most promising biodegradable alternative to replace conventionalpetrochemical-based polymers in manufacturing high performance materials. Here we review the main methods to obtain polylactic acid and briefly discuss its functionalization and application in the field of controlled drug release. We conducted a bibliographic search of scientific databases and summarized the results of the research carried out by our group. We show that the most commonly used PLA modifications in drug delivery systems are functionalization with glycolic acid (GA) and polyethylene glycol (PEG) through copolymerization or blending, where the use of compatibilizers is essential for good adhesion. Active vectorization is discussed as its choice depends on the size of the nanoparticle and the type of disease to be treated.

Advances in Biomedical and Environmental Applications of Magnetic Hydrogels

Hydrogels have been the focus of research across disciplines or subject perspectives owing to their distinctive chemical, physical, and mechanical characteristics. Hydrogels have been leveraged for their biocompatibility and attractive adhesion or adsorption behavior. Conventional hydrogels suffer from frequent entrapment due to low controllability, limited responsiveness, and weak actuation properties. Magnetic hydrogels address many of these concerns and offer a rapid magnetic response and precise temporal and spatial control. The structural and functional features of magnetic hydrogels can address overlapping requirements in biomedical and environmental applications. The focus of this review is on the progress made in the use of magnetic hydrogels. Specifically, their applications in controlled drug delivery as contrast agents in magnetic resonance imaging and in the treatment and remediation of wastewater are discussed. The first part of the review delineates strategies for preparing magnetic hydrogels and the advantages of each approach. The second part of the review describes a variety of biomedical and environmental applications for highlighting the convergent functionalities of magnetic hydrogels that are relevant to each domain. The challenges in the use of magnetic hydrogels and prospective applications are also included in the review.

Development of Polymer Membrane using Chitosan/ Hydroxyethyl Cellulose for Controlled Release of Bioactive Agent

The present work describes the fabrication of a polymer membrane using chitosan and hydroxyethyl cellulose by the solvent casting evaporation method. The membranes were loaded with curcumin which is taken as a model bioactive agent for controlled drug delivery applications. The developed membranes were characterized by different techniques such as FTIR, DSC, TGA, XRD and SEM. Curcumin-loaded membranes were tested in in vitro drug release studies in a phosphate buffer solution of pH 7.4 at 37 oC to see how quickly they swelled. The drug-encapsulated membranes have a high release rate of roughly 90% for up to 16 hours. The developed membranes follow a non-Fickian diffusion mechanism with values of ‘n’ ranging from 0.506 to 0.624. The results suggest that our developed membranes warrant further development for drug delivery applications.

Evaluating the in vivo stability of water-soluble PEG-PLA copolymers using FRET imaging

Biodegradable and biocompatible polymer materials with tunable physical properties present a great interest for controlled drug delivery applications. A good example is BEPO®, a clinical-stage in situ-forming depot technology based on the utilization of a blend of poly(ethylene glycol)-b-poly(D,L-lactic acid) (PEG-PLA) diblock and triblock amphiphilic copolymers dissolved in an organic solvent. Once injected, this technology will form a bioresorbable solid polymer depot that will allow the release of a drug from weeks to months. The safety of the final degradation products from this technology, i.e., PEG and lactic acid, is well-documented. However, little information exists about the fate of intermediate degradants, specifically of water-soluble PEG-PLA chains where the molecular weights of the PLA block are short. Herein, we designed a Förster Resonance Energy Transfer (FRET) system for short copolymers, suitable for longitudinal in vivo imaging in the subcutaneous space, allowing to follow the stability of these products. Our results confirm that these species, that might be leaked from BEPO® depots during degradation, are rapidly hydrolyzed in the subcutaneous space of mice, forming approved products by Health Authorities, i.e., PEG and PLA homopolymers and/or lactic acid.

Structural and mechanical properties of folded protein hydrogels with embedded microbubbles.

Globular folded proteins are powerful building blocks to create biomaterials with mechanical robustness and inherent biological functionality. Here we explore their potential as advanced drug delivery scaffolds, by embedding microbubbles (MBs) within a photo-activated, chemically cross-linked bovine serum albumin (BSA) protein network. Using a combination of circular dichroism (CD), rheology, small angle neutron scattering (SANS) and microscopy we determine the nanoscale and mesoscale structure and mechanics of this novel multi-composite system. Optical and confocal microscopy confirms the presence of MBs within the protein hydrogel, their reduced diffusion and their effective rupture using ultrasound, a requirement for burst drug release. CD confirms that the inclusion of MBs does not impact the proportion of folded proteins within the cross-linked protein network. Rheological characterisation demonstrates that the mechanics of the BSA hydrogels is reduced in the presence of MBs. Furthermore, SANS reveals that embedding MBs in the protein hydrogel network results in a smaller number of clusters that are larger in size (∼16.6% reduction in number of clusters, 17.4% increase in cluster size). Taken together, we show that MBs can be successfully embedded within a folded protein network and ruptured upon application of ultrasound. The fundamental insight into the impact of embedded MBs in protein scaffolds at the nanoscale and mesoscale is important in the development of future platforms for targeted and controlled drug delivery applications.

Design of ciprofloxacin impregnated dietary fiber psyllium-moringa gum-alginate network hydrogels via green approach for use in gastro-retentive drug delivery system

In order to improve the pharmacokinetic deficiencies and bioavailability of therapeutic agent used in the upper gastro intestinal tract (GIT), herein this article gastro-retentive drug delivery system (DDS) were developed via green approach from medicinally important polysaccharides psyllium, moringa gum and alginate. The antibiotic drug ciprofloxacin was impregnated into DDS. These polymeric DDS were characterized by cryo-SEMs, FTIR, 13C NMR and XRD analysis. The simulated gastric fluid uptake was reduced with rise in crosslinking during ionotropic gelation. The diffusion of ciprofloxacin was non-Fickian and it was fitted in Korsmeyer-Peppas model. The porous nature of the crosslinked network hydrogel beads was observed in cryo SEM images. XRD indicated the amorphous nature of the hydrogel beads. The haemolytic index value of beads was observed less than 5%. The results of the polymer interactions with blood indicated the non-hemolytic nature of the polymers with their suitability for controlled drug delivery applications. The antioxidant property indicated 64.03 ± 0.29% DPPH radicals scavenging assay of the beads. Overall, anti-ulcer activity of the DDS for gastric ulceration could be enhanced due to slow release of ciprofloxacin drug from drug delivery carrier which itself has antiulcer therapeutic potential due to composed dietary fibers psyllium-moringa gum-alginate.

Wireless electromechanical enantio-responsive valves.

Microfluidic valves based on chemically responsive materials have gained considerable attention in recent years. Herein, a wireless enantio-responsive valve triggered by bipolar electrochemistry combined with chiral recognition is reported. A conducting polymer actuator functionalized with the enantiomers of an inherently chiral oligomer was used as bipolar valve to cover a tube loaded with a dye and immersed in a solution containing chiral analytes. When an electric field is applied, the designed actuator shows a reversible cantilever-type deflection, allowing the release of the dye from the reservoir. The tube can be opened and closed by simply switching the polarity of the system. Qualitative results show the successful release of the colorant, driven by chirality and redox reactions occurring at the bipolar valve. The device works well even in the presence of chemically different chiral analytes in the same solution. These systems open up new possibilities in the field of microfluidics, including also controlled drug delivery applications.

Impregnating graphene oxide into polyvinylsulphonic acid–sterculia gum hydrogels to modulate antibiotic drug vancomycin interactions for controlled drug delivery applications

Recently, graphene oxide (GO) has been well explored for biomedical applications due to its stability, biocompatibility and large surface area. Herein this research, GO incorporated sterculia gum-poly(VSA) hydrogels were designed by encapsulating vancomycin antibiotic drug for use in colon specific drug delivery.

Ibuprofen tagged imine RT-COF-1 as customisable vehicle for controlled drug delivery application

Here, we have been synthesized imine linked covalent organic framework (RT-COF-1) using 1,3,5-tris(4-aminophenyl) benzene (TAPB) and 1,3,5-benzenetricarbaldehyde (BTCA) in 1:1 ratio with catalytic amount of glacial acetic acid at room temperature. Synthesized RT-COF1 has been confirmed using Powder X-ray diffraction (PXRD), Field Emission Scanning Electron Microscopy (FESEM), UV -Vis Spectroscopy, Photoluminescence Spectroscopy, Fourier transform infrared spectroscopy (FTIR), and BET Surface area analyzer. Then, synthesised RT-COF1 has been tagged to model drug i.e., ibuprofen (IBU) using simple coordination chemistry. The drug conjugated i.e., [email protected] was confirmed through UV and IR spectroscopy techniques. Importantly, the lone pair of electrons on nitrogen atom present in RT-COF1 forms hydrogen bonding with the model drug molecules. Prominently, the model drug profile i.e., loading and release rate has been analysed using spectroscopic analysis.

Photoswitchable polyurethane based nanoaggregates for on-command release of noncovalent guest molecules

The self-assembly of light responsive amphiphilic polymers has been of great interest in spatially and temporally controlled drug delivery applications. In this article, we report the design, synthesis and characterization of amphiphilic main chain azobenzene polyurethane as well as its self-assembly in aqueous milieu. This polymer self-assembles into micellar nanostructure (investigated by dynamic light scattering and scanning electron microscopy imaging) and shows hydrophobic guest sequestration with high encapsulation stability (probed by FRET experiment). The photoswitching (trans-to-cis) of these nanoaggregates has been investigated by irradiation with UV light (λ = 365 nm), which results significant change in the hydrophobic environment and molecular arrangement in the micellar core. This leads to encapsulated guest release in a controlled manner as probed by UV-vis spectroscopy. Furthermore, we demonstrated tumor-relevant pH (∼6.5-6.8) induced surface charge modulation (neutral to positive) by zeta potential measurements. The light responsive guest release and pH-specific charge modulation, we believe, will have significant impact in development of delivery systems for targeted and controlled delivery of drug molecules.

Synthesis of a New Molecular Imprinted Polymer for Oxycodone Opioid and Its Formulation for Transdermal Controlled Drug Delivery Application: A Joint Experimental and Quantum Chemical Study

AbstractIn the present project, a molecular imprinted polymer (MIP) was synthesized by using oxycodone (as the molecular template as well as the guest drug). The precipitation polymerization approach was used for preparation of the nano‐composites. Methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and 2,2‐azobisissobutyronitrile (AIBN), were used as the functional monomer, the crosslinker, and as the photoinitiator, respectively. Moreover, to decrease the release rate of the drug, the bacterial cellulose (BC) was used in formulation of MIP contained‐transdermal patch. The release study of the drug by high performance liquid chromatography (HPLC) system (fitted with the Higuchi expression) has indicated that the MIP‐BC is a good candidate for the controlled transdermal drug delivery systems (TDDS). Finally, both the MIP‐, and the non‐molecular imprinted polymers (NIP)‐drug systems were designed and studied by the density functional theory (DFT) quantum chemical method, to investigate the potential energy surface (PES), structural properties, and adsorption behavior in the molecular view. The results showed that the formation of MIP‐oxycodone (−12.85 kcal mol−1) system is more favorable than the formation of the NIP‐oxycodone one (−11.35 kcal mol−1) (due to more hydrogen bonds, and polar interactions).

Genetically Engineered Viral Vectors and Organic-Based Non-Viral Nanocarriers for Drug Delivery Applications.

Conventional drug delivery systems are challenged by concerns related to systemic toxicity, repetitive doses, drug concentrations fluctuation, and adverse effects. Various drug delivery systems are developed to overcome these limitations. Nanomaterials are employed in a variety of biomedical applications such as therapeutics delivery, cancer therapy, and tissue engineering. Physiochemical nanoparticle assembly techniques involve the application of solvents and potentially harmful chemicals, commonly at high temperatures. Genetically engineered organisms have the potential to be used as promising candidates for greener, efficient, and more adaptable platforms for the synthesis and assembly of nanomaterials. Genetically engineered carriers are precisely designed and constructed in shape and size, enabling precise control over drug attachment sites. The high accuracy of these novel advanced materials, biocompatibility, and stimuli-responsiveness, elucidate their emerging application in controlled drug delivery. The current article represents the research progress in developing various genetically engineered carriers. Organic-based nanoparticles including cellulose, collagen, silk-like polymers, elastin-like protein, silk-elastin-like protein, and inorganic-based nanoparticles are discussed in detail. Afterward, viral-based carriers are classified, and their potential for targeted therapeutics delivery is highlighted. Finally, the challenges and prospects of these delivery systems are concluded.

Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight.

Polyanhydrides have been synthesized for decades by melt-polycondensation of diacid monomers and 5 to >10 times mole excess acetic anhydride to diacid monomers to form polymers with a polydispersity ranging from 2.5 to 6 and low reproducibility. Hydrophobic segments in polyanhydrides are beneficial to hinder the characteristic hydrolytic cleavage of an anhydride bond that provides stable polyanhydrides at room temperature. The objective of this work is to synthesize aliphatic polyanhydrides with various hydrophobic segments, controllable and reproducible molecular weight, and low polydispersity that are essential for potential use as drug carriers. A series of polyanhydrides of suberic, azelaic, sebacic, and dodecanedioic acids with controlled molecular weight, reduced polydispersity, and standard deviation of molecular weights, have been synthesized. All synthesized polyanhydrides were thoroughly characterized by NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography. Molecular weights of the synthesized polyanhydrides are highly controllable, depending on the degree of activation of the dicarboxylic acid monomers, i.e., the amount of acetic anhydride used during synthesis. Polyanhydrides have been synthesized in triplicate by melt-polycondensation, using various mole ratios of acetic anhydride to diacids. The standard deviation of the molecular weights of the polyanhydrides is minute when using 1 equivalent of acetic anhydride during the activation of dicarboxylic acids, whereas if excess acetic anhydride is used, the standard deviation is very high. The effect of safe and natural inorganic catalysts, Calcium oxide, Zinc oxide, and Calcium carbonate on polymerization is also studied. As-synthesized poly(sebacic acid) can offer convenience to use in controlled drug delivery applications. In vitro drug release study using Temozolamide (TMZ), a medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma, shows 14% TMZ release after the first hour and 70% release over one day from the poly(sebacic acid) wafers.