Controlled Release Profile Research Articles

Mucoadhesive 3D printed vaginal ovules to treat endometriosis and fibrotic uterine diseases

Gynaecological health is a neglected field of research that includes conditions such as endometriosis, uterine fibroids, infertility, viral and bacterial infections, and cancers. There is a clinical need to develop dosage forms for gynecological diseases that increase efficacy and reduce side effects and explore new materials with properties tailored to the vaginal mucosa and milieu. Here, we developed a 3D printed semisolid vaginal ovule containing pirfenidone, a repurposed drug candidate for endometriosis. Vaginal drug delivery allows direct targeting of the reproductive organs via the first uterine pass effect, but vaginal dosage forms can be challenging to self-administer and retain in situ for periods of more than 1–3 h. We show that a semisoft alginate-based vaginal suppository manufactured using semisolid extrusion additive manufacturing is superior to vaginal ovules made using standard excipients. The 3D-printed ovule showed a controlled release profile of pirfenidone in vitro in standard and biorelevant release tests, as well as better mucoadhesive properties ex vivo. An exposure time of 24 h of pirfenidone to a monolayer culture of an endometriotic epithelial cell line, 12Z, is necessary to reduce the cells’ metabolic activity, which demonstrates the need for a sustained release formulation of pirfenidone. 3D printing allowed us to formulate mucoadhesive polymers into a semisolid ovule with controlled release of pirfenidone. This work enables further preclinical and clinical studies into vaginally administered pirfenidone to assess its efficacy as a repurposed endometriosis treatment.

Co-delivery of paclitaxel and regorafenib by F127/TPGS mixed micelles for triple negative breast cancer treatment

Finding effective treatment for triple negative breast cancer (TNBC) is highly challenging. This study aims to design a co-delivery system to suppress TNBC cells’ growth and migration. Paclitaxel (PTX) and regorafenib (REG) co-loaded mixed micelles (PTX-REG-MMs) were developed. The critical micelle concentration (CMC) of micelles composed of F127 and TPGS (4:1) was 0.028 mg/ml. The morphological studies by TEM showed a core-shell micelle structure with a size of around 25 nm. The size of PTX-REG-MM by dynamic laser scattering (DLS) was about 29.96 ± 2.31, with the polydispersity index (PDI) about 0.27 ± 0.11. PTX and REG encapsulation efficacy% (EE) were found to be 42.93% ± 1.33 and 89.88% ± 3.99, respectively. In vitro release study showed a controlled release profile. Several cellular tests such as MTT, colony-forming, and wound healing assay showed the ability of PTX-REG-MM to inhibit proliferation and migration of TNBC cells (MDA-MB-231). Furthermore, mixed micelle exhibited high cellular uptake in the cancer cells. In conclusion, PTX-REG-MM showed promising potential to enhance the therapeutic efficacy of PTX and overcome multi-drug resistance (MDR).

Controlled Release and Cell Viability of Ketoconazole Incorporated in PEG 4000 Derivatives.

In recent years, polymeric materials have been gaining prominence in studies of controlled release systems to obtain improvements in drug administration. These systems present several advantages compared with conventional release systems, such as constant maintenance in the blood concentration of a given drug, greater bioavailability, reduction of adverse effects, and fewer dosages required, thus providing a higher patient compliance to treatment. Given the above, the present work aimed to synthesize polymeric matrices derived from polyethylene glycol (PEG) capable of promoting the controlled release of the drug ketoconazole in order to minimize its adverse effects. PEG 4000 is a widely used polymer due to its excellent properties such as hydrophilicity, biocompatibility, and non-toxic effects. In this work, PEG 4000 and derivatives were incorporated with ketoconazole. The morphology of polymeric films was observed by AFM and showed changes on the film organization after drug incorporation. In SEM, it was possible to notice spheres that formed in some incorporated polymers. The zeta potential of PEG 4000 and its derivatives was determined and suggested that the microparticle surfaces showed a low electrostatic charge. Regarding the controlled release, all the incorporated polymers obtained a controlled release profile at pH 7.3. The release kinetics of ketoconazole in the samples of PEG 4000 and its derivatives followed first order for PEG 4000 HYDR INCORP and Higuchi for the other samples. Cytotoxicity was determined and PEG 4000 and its derivatives were not cytotoxic.

Darifenacin Self-assembled Liquid Crystal Cubic Nanoparticles: a Sustained Release Approach for an Overnight Control of Overactive Bladder

The current study is regarding the development and characterization of Darifenacin-loaded self-assembled liquid crystal cubic nanoparticles (LCCN). An anhydrous approach was used for the preparation of these cubic nanoparticles using a hydrotropic agent (propylene glycol), with minimal energy input. Upon dispersion in aqueous medium, the system was successfully transformed to cubosomal nanoparticles counterpart as depicted by transmission electron micrographs. A Box-Behnken design was used to optimize formulation variables, namely A: amount of GMO, B: amount of Pluronic F127, C: amount of PG, and D: amount of HPMC. The design has generated 29 formulae which were tested regarding drug content uniformity, dispersibility in water, particle size, zeta potential, polydispersity index, and in vitro release behavior. The numerical optimization algorithms have generated an optimized formula with high desirability ≈ 1. The optimized formula displayed small particle size, good homogeneity, and zeta potential along with controlled in vitro release profile and ex vivo permeation through rabbit intestine. Thus, self-assembled LCCN might offer an alternative anhydrous approach for the preparation of cubosomal nanoparticles with controlled release profile for a possibly better control of overactive bladder syndrome which tremendously affect the overall life quality.Graphical

Development of Carvedilol-Loaded Albumin-Based Nanoparticles with Factorial Design to Optimize In Vitro and In Vivo Performance.

Carvedilol, an anti-hypertensive medication commonly prescribed by healthcare providers, falls under the BCS class II category due to its low-solubility and high-permeability characteristics, resulting in limited dissolution and low absorption when taken orally. Herein, carvedilol was entrapped into bovine serum albumin (BSA)-based nanoparticles using the desolvation method to obtain a controlled release profile. Carvedilol-BSA nanoparticles were prepared and optimized using 32 factorial design. The nanoparticles were characterized for their particle size (Y1), entrapment efficiency (Y2), and time to release 50% of carvedilol (Y3). The optimized formulation was assessed for its in vitro and in vivo performance by solid-state, microscopical, and pharmacokinetic evaluations. The factorial design showed that an increment of BSA concentration demonstrated a significant positive effect on Y1 and Y2 responses with a negative effect on Y3 response. Meanwhile, the carvedilol percentage in BSA nanoparticles represented its obvious positive impact on both Y1 and Y3 responses, along with a negative impact on Y2 response. The optimized nanoformulation entailed BSA at a concentration of 0.5%, whereas the carvedilol percentage was 6%. The DSC thermograms indicated the amorphization of carvedilol inside the nanoparticles, which confirmed its entrapment into the BSA structure. The plasma concentrations of carvedilol released were observable from optimized nanoparticles up to 72 h subsequent to their injection into rats, revealing their longer in vivo circulation time compared to pure carvedilol suspension. This study offers new insight into the significance of BSA-based nanoparticles in sustaining the release of carvedilol and presents a potential value-added in the remediation of hypertension.

Transdermal delivery of doxorubicin and methotrexate from polyelectrolyte three layer nanoparticle of graphene oxide/polyethyleneimine/dextran sulphate for chemotherapy: In vitro and in vivo studies

In the present work, novel dual drug loaded - anionic graphene oxide/cationic polyethyleneimine/poly anionic dextran sulfate (GO/PEI/DS) was synthesized by a layer-by-layer self-assembly technique for transdermal anti-cancer drug delivery. Doxorubicin (DOX) was loaded onto folic acid conjugated graphene oxide (GO) and methotrexate (MTX) was loaded onto dextran sulfate (DS). The drug carrier was characterized by fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, dynamic light scattering analysis, scanning electron microscopy, atomic force microscopy, transmission electron microscopy, zeta-potential analysis, drug loading and encapsulation efficiency, equilibrium swelling studies, in vitro drug release studies, hemocompatibility assays, in vitro cytotoxicity assay, skin irritation studies, ex vivo skin permeation studies and in vivo pharmacokinetic studies.The cytotoxicity of synthesized materials was evaluated against MCF-7 breast cancer cells using an MTT assay and apoptosis assay. The synergistic effect of DOX and MTX to inhibit the growth of cancer cells was also confirmed. The final dual drug-loaded carrier showed a cell viability of 36.38 % towards MCF-7 cancer cells while it showed a cell viability of >87.65 % towards normal L929 cell lines. The in vivo pharmacokinetic studies in Wistar rats through oral and transdermal routes of administration, the transdermal route of administration of dual drug-loaded material provided a sustained and prolonged drug existence in the blood circulation system. The mean residence time of drugs in the bloodstream via oral administration was 83.98 ± 3.71 h, while that of the transdermal route of administration was 149.62 ± 6.11 h. The results revealed that the synthesized dual drug-loaded material showed a good pH-dependent controlled and sustained release profile for both DOX and MTX via the transdermal route of administration in comparison with oral delivery.

A Novel Strategy as a Potential Rapid Therapy Modality in the Treatment of Corneal Ulcers: Fluconazole/Vancomycin Dual Drug‐Loaded Nanofibrous Patches

AbstractCorneal ulcer, which is brought on by a breach in the epithelial barrier, is a dangerous infection of the avascular corneal stroma. New treatment strategies are needed, suppressing the aggressive nature of the disease and including a combination of different drugs. In this study, vancomycin (VAN) and fluconazole (FLU) dual‐drug loaded dual‐layered polyvinyl alcohol and gelatin (PVA/GEL) nanofibrous patches are produced by electrospinning. Scanning electron microscopy (SEM) images show smooth surfaces are obtained for both pure and drug‐loaded nanofibrous patches. The tensile test results report that loading the FLU and VAN separately into the PVA/GEL patches decrease both the tensile strength and elongation at break and it is further reduced when combining two drug‐loaded layers in one patch. According to drug release results, the FLU and VAN‐loaded nanofibrous patches show a controlled release profile extending up to 96 h. Moreover, PVA/GEL/FLU, PVA/GEL/VAN, and PVA/GEL/FLU/VAN nanofibrous patches display significant antimicrobial activity against Candida albicans and Staphylococcus aureus. SEM, 4'‐6diamidynofenyloindol (DAPI) staining, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay show that PVA/FLU and PVA/GEL/FLU/VAN nanofibrous patches have a superior effect on NIH3T3 cell spreading and proliferation. The novelty of this study lays in the development of a potential dual drug rapid treatment for corneal ulcers of aggressive nature.

Sustained-Release Powders Based on Polymer Particles for Pulmonary Delivery of Beclomethasone Dipropionate in the Treatment of Lung Inflammation.

Inhaled corticosteroids are the mainstay in the management of lung inflammation associated to chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Nonetheless, available inhalation products are mostly short-acting formulations that require frequent administrations and do not always produce the desired anti-inflammatory effects. In this work, the production of inhalable beclomethasone dipropionate (BDP) dry powders based on polymeric particles was attempted. As starting material, the PHEA-g-RhB-g-PLA-g-PEG copolymer was chosen, obtained by grafting 0.6, 2.4 and 3.0 mol%, respectively, of rhodamine (RhB), polylactic acid (PLA) and polyethylene glycol 5000 (PEG) on alpha,beta-poly(N-2-hydroxyethyl)DL-aspartamide (PHEA). The drug was loaded into the polymeric particles (MP) as an inclusion complex (CI) with hydroxypropyl-cyclodextrin (HP-β-Cyd) (at a stoichiometric ratio of 1:1) or as free form. The spray-drying (SD) process to produce MPs was optimized by keeping the polymer concentration (0.6 wt/vol%) constant in the liquid feed and by varying other parameters such as the drug concentration. The theoretical aerodynamic diameter (daer) values among the MPs are comparable and potentially suitable for inhalation, as confirmed also through evaluation of the experimental mass median aerodynamic diameter (MMADexp). BDP shows a controlled release profile from MPs that is significantly higher (more than tripled) than from Clenil®. In vitro tests on bronchial epithelial cells (16HBE) and adenocarcinomic human alveolar basal epithelial cells (A549) showed that all the MP samples (empty or drug-loaded) were highly biocompatible. None of the systems used induced apoptosis or necrosis. Moreover, the BDP loaded into the particles (BDP-Micro and CI-Micro) was more efficient than free BDP to counteract the effects of cigarette smoke and LPS on release of IL-6 and IL-8.

A pH and Temperature Dual-Responsive Microgel-Embedded, Adhesive, and Tough Hydrogel for Drug Delivery and Wound Healing

Stimuli-responsive hydrogels have attracted much attention over the past decade for potential bioengineering applications such as wound dressing and drug delivery. In this work, a pH and temperature dual-responsive microgel-embedded hydrogel has been fabricated by incorporating poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAAm-co-AAc) based microgel particles into polyacrylamide (PAAm)/chitosan (CS) semi-interpenetrating polymer network (semi-IPN), denoted as microgel@PAM/CS. The resultant hydrogel possesses excellent mechanical properties including stretchability, compressibility, and elasticity. In addition, the microgel@PAM/CS hydrogels can tightly adhere to the surfaces of a variety of tissues such as porcine skin, kidney, intestine, liver, and heart. Moreover, it shows controlled dual-drug release profile of both bovine serum albumin (BSA) (as a model protein) and sulfamethoxazole (SMZ), an antibiotic. Excellent antimicrobial properties are obtained for SMZ-loaded microgel@PAM/CS hydrogels. Compared with traditional drug administration methods such as by mouth, injection, and inhalation, the microgel@PAM/CS hydrogels possess advantages such as higher drug loading efficiency (by more than 80%) and controllable and sustained (over 48 h) release. The microgel@PAM/CS hydrogels can significantly enhance the wound healing process. This work provides a facile approach for the fabrication of multifunctional stimuli-responsive microparticle-embedded hydrogels with semi-IPN structures, and the as-prepared microgel@PAM/CS hydrogels have great potential for applications as smart wound dressing materials in biomedical engineering.

Polymer coated polymeric microneedles for intravitreal delivery of dexamethasone

The polymer coated polymeric (PCP) microneedles (MNs) is a novel approach for controlled delivery of drugs (without allowing release of the excipients) to the target site. PCP MNs was explored as an approach to deliver the drug intravitreally to minimize the risks associated with conventional intravitreal injections. The core MNs was fabricated with polyvinyl pyrrolidone K30 (PVP K30) and coating was with Eudragit E100. Preformulation studies revealed that the films prepared using Eudragit E 100 exhibited excellent integrity in the physiological medium after prolonged exposure. FTIR studies were performed to investigate the possible interaction between the API and the polymer. The PCP MNs fabricated with different drug loads (dexamethasone sodium phosphate) were subjected to in vitro drug release studies. The drug release from uncoated MNs was instantaneous and complete. On the other hand, a controlled release profile was observed in case of PCP MNs. Likewise, even in the ex vivo porcine eye model, the drug release was gradual into the vitreous humor in case of PCP MNs. The uncoated microneedles released all the drug instantaneously where the PCP MNs retarded the release up to 3 h.

Fabrication of Polymeric Hydrogels Containing Esomeprazole for Oral Delivery: In Vitro and In Vivo Pharmacokinetic Characterization

Hydrogel is one of the most interesting and excellent candidates for oral drug delivery. The current study focuses on formulation development of hydrogels for controlled oral delivery of esomeprazole. The hydrogels were prepared by solution casting method by dissolving polymers in Polyvinyl alcohol (PVA) solution. Calcium alginate, Hydroxyl propyl methylcellulose (HPMC), acrylic acid and chondroitin sulfate were used in the preparation of hydrogels. Fourier transform infrared (FTIR) analysis showed no incompatibilities between drug and excipients used in the preparation of formulations. The hydrogels were characterized for size and surface morphology. Drug encapsulation efficiency was measured by Ultraviolet-visible (UV-VIS) spectroscopy. In vitro release studies were carried out using dissolution apparatus. The formulated hydrogels were then compared with the marketed product in vivo using rabbits. The result indicates that prepared hydrogels have a uniform size with a porous surface. The esomeprazole encapsulation efficiency of the prepared hydrogels was found to be 83.1 ± 2.16%. The esomeprazole-loaded hydrogel formulations showed optimum and Pharmacopeial acceptable range swelling behavior. The release of esomeprazole is controlled for 24 h (85.43 ± 0.32% in 24 h). The swelling and release of drug results make the prepared hydrogels a potential candidate for the controlled delivery of esomeprazole. The release of the drug from prepared hydrogel followed the super case transport-2 mechanism. The in vivo studies showed that prepared hydrogel formulations showed controlled and prolonged release of esomeprazole as compared to drug solution and marketed product. The formulations were kept for stability studies; there was no significant change observed in physical parameters, i.e., (appearance, color change and grittiness) at 40 °C ± 2/75% ± RH. There was a negligible difference in the drug content observed after the stability study suggested that all the formulations are stable under the given conditions for 60 days. The current study provides a valuable perspective on the controlled release profile of Hydroxyl propyl methylcellulose (HPMC) and calcium alginate-based esomeprazole hydrogels.

Investigation of the antitumor effect on breast cancer cells of the electrospun amygdalin-loaded poly(l-lactic acid)/poly(ethylene glycol) nanofibers

In this study, PLA/PEG nanofibers (NFs) loaded with amygdalin (AMG) and bitter almond kernels extract were produced by electrospinning to prevent local breast cancer recurrence, and the effect of produced NFs on the MCF-7 cell line was investigated in vitro. The electrospun NFs were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis (DSC) and tensile strength and physical analyzes were performed. Loading of AMG to nanofibers increased fiber diameters from 827.93 ± 174.507 nm to 1855.32 ± 291.057 μm. When drug release results were analyzed, the NFs showed a controlled release profile extending up to 10 h. The encapsulation efficiency of AMG-loaded NFs was calculated at 100 ± 0,01 %, 94 ± 0,02 %, and 88 ± 0,02 %. When in vitro cytotoxicity results were analyzed, showed that all NFs are effective in inducing cytotoxicity against MCF-7 breast cancer cells. Importantly, 20 mg AMG-loaded NFs displayed effectively higher cytotoxic effects against breast cancer cells relative to the other NFs. Considering all the results, AMG-loaded NFs can give sustained release of drugs at the local sites. Therefore, AMG-loaded nanofibers can reduce the risk of local recurrence of cancer after surgery and can be directly implanted into solid tumor cells for treatment.

2-Hydroxyethyl Methacrylate/Gelatin/Alginate Scaffolds Reinforced with Nano TiO2 as a Promising Curcumin Release Platform.

The idea of this study was to create a new scaffolding system based on 2-hydroxyethyl methacrylate, gelatin, and alginate that contains titanium(IV) oxide nanoparticles as a platform for the controlled release of the bioactive agent curcumin. The innovative strategy to develop hybrid scaffolds was the modified porogenation method. The effect of the scaffold composition on the chemical, morphology, porosity, mechanical, hydrophilicity, swelling, degradation, biocompatibility, loading, and release features of hybrid scaffolds was evaluated. A porous structure with interconnected pores in the range of 52.33-65.76%, favorable swelling capacity, fully hydrophilic surfaces, degradability to 45% for 6 months, curcumin loading efficiency above 96%, and favorable controlled release profiles were obtained. By applying four kinetic models of release, valuable parameters were obtained for the curcumin/PHEMA/gelatin/alginate/TiO2 release platform. Cytotoxicity test results depend on the composition of the scaffolds and showed satisfactory cell growth with visible cell accumulation on the hybrid surfaces. The constructed hybrid scaffolds have suitable high-performance properties, suggesting potential for further in vivo and clinical studies.

Carbon nanotubes as a nitric oxide nano-reservoir improved the controlled release profile in 3D printed biodegradable vascular grafts

Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system improves biocompatibility by using the NO effect to promote endothelial cell (EC) migration and proliferation while preventing bacterial infection. To circumvent the instability of NO donors and to prolong NO releasing, S-nitroso-N-acetyl-d-penicillamine (SNAP) as a NO donor was loaded in multi-walled carbon nanotubes (MWCNTs). Successful loading was confirmed with a maximum SNAP amount of ~ 5% (w/w) by TEM, CHNS analysis and FTIR spectra. SDVGs were 3D printed from polycaprolactone (PCL) and coated with a 1:1 ratio of polyethylene glycol and PCL dopped with different concentrations of SNAP-loaded matrix and combinations of MWCNTs-OH. Coating with 10% (w/w) SNAP-matrix-10% (w/w) SNAP-MWCNT-OH showed a diminished burst release and 18 days of NO release in the range of 0.5–4 × 10–10 mol cm−2 min−1 similar to the NO release from healthy endothelium. NO-releasing SDVGs were cytocompatible, significantly enhanced EC proliferation and migration and diminished bacterial viability. The newly developed SNAP-loaded MWCNT-OH has a great potential to develop NO releasing biomaterials with a prolonged, controlled NO release promoting in-situ endothelialization and tissue integration in vivo, even as an approach towards personalized medicine.

A Micro-In-Macro Gastroretentive System for the Delivery of Narrow-Absorption Window Drugs.

A micro-in-macro gastroretentive and gastrofloatable drug delivery system (MGDDS), loaded with the model-drug ciprofloxacin, was developed in this study to address the limitations commonly experienced in narrow-absorption window (NAW) drug delivery. The MGDDS, which consists of microparticles loaded in a gastrofloatable macroparticle (gastrosphere) was designed to modify the release of ciprofloxacin, allowing for an increased drug absorption via the gastrointestinal tract. The prepared inner microparticles (1-4 µm) were formed by crosslinking chitosan (CHT) and Eudragit® RL 30D (EUD), with the outer gastrospheres prepared from alginate (ALG), pectin (PEC), poly(acrylic acid) (PAA) and poly(lactic-co-glycolic) acid (PLGA). An experimental design was utilized to optimize the prepared microparticles prior to Fourier Transition Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM) and in vitro drug release studies. Additionally, the in vivo analysis of the MGDDS, employing a Large White Pig model and molecular modeling of the ciprofloxacin-polymer interactions, were performed. The FTIR results determined that the crosslinking of the respective polymers in the microparticle and gastrosphere was achieved, with the SEM analysis detailing the size of the microparticles formed and the porous nature of the MGDDS, which is essential for drug release. The in vivo drug release analysis results further displayed a more controlled ciprofloxacin release profile over 24 h and a greater bioavailability for the MGDDS when compared to the marketed immediate-release ciprofloxacin product. Overall, the developed system successfully delivered ciprofloxacin in a control-release manner and enhanced its absorption, thereby displaying the potential of the system to be used in the delivery of other NAW drugs.

In situ forming dialdehyde xanthan gum-gelatin Schiff-base hydrogels as potent controlled release fertilizers

Controlled release fertilizer (CRF) hydrogels have blossomed into promising materials in agriculture owing to the sustained release of the fertilizer and also as soil conditioner. Apart from the traditional CRF hydrogels; Schiff-base hydrogels have garnered significant thrust that release nitrogen slowly in addition to reducing the environmental pollution. Herein, we have fabricated Schiff-base CRF hydrogels composed of dialdehyde xanthan gum (DAXG) and gelatin. The formation of the hydrogels was accomplished via the simplistic in situ crosslinking reaction between the aldehyde groups of DAXG and the amino groups of gelatin. The hydrogels acquired a compact network upon increasing the DAXG content in the matrix. The phytotoxic assay on different plants indicated the hydrogels to be nontoxic. The hydrogels demonstrated good water-retention behaviour in soil, along with reusability even after 5 cycles. A controlled release profile for urea was evident from the hydrogels wherein macromolecular relaxation played a crucial role in the release mechanism. Growth assays on Abelmoschus esculentus (Okra) plant presented an intuitive evaluation on the growth and water-holding capacity of the CRF hydrogel. The present work demonstrated a facile preparation of CRF hydrogels to enhance the utilization of urea and retain soil humidity as fertilizer carriers.

Effect of cold plasma treatment on polylactic acid and polylactic acid/poly (ethylene glycol) films developed as a drug delivery system for streptomycin sulfate

Polylactic acid (PLA) being a renewable polyester have extensively researched in the biomedical field due to its non-toxicity, high biocompatibility, and easy processing properties. However, low functionalization ability and hydrophobicity limit its applications and hence demands physical and chemical modifications to overcome these limitations. Cold plasma treatment (CPT) is frequently used to improve the hydrophilic properties of PLA-based biomaterials. This provides an advantage to obtain a controlled drug release profile in drug delivery systems. The rapid drug release profile may be advantageous in some applications such as wound application. The main objective of this study is to determine the effects of CPT on PLA or PLA@polyethylene glycol (PLA@PEG) porous films fabricated by solution casting method for use as a drug delivery system with a rapid release profile. The physical, chemical, morphological and drug release properties of PLA and PLA@PEG films, such as surface topography, thickness, porosity, water contact angle (WCA), chemical structure, and streptomycin sulfate release properties, after CPT were systematically investigated. XRD, XPS and FTIR results showed that oxygen-containing functional groups were formed on the film surface with CPT without changing the bulk properties. Along with the changes in the surface morphology such as surface roughness and porosity, the new functional groups provide the films hydrophilic properties by reducing the water contact angle. The improved surface properties enabled the selected model drug, streptomycin sulfate, to exhibit a faster release profile with drug-released mechanism fitted by first order kinetic model. Considering all the results, the prepared films showed an enormous potential for future drug delivery applications, especially in wound application where rapid drug release profile is an advantage.

Fabricating transdermal film formulations of montelukast sodium with improved chemical stability and extended drug release

Montelukast Sodium (MK) is a leukotriene receptor antagonist, an oral drug generally prescribed to control chronic asthma symptoms. This research aims to provide the transdermal delivery of this drug in a controlled release profile as a better mode of drug delivery, specifically for the pediatric and elderly population. Transdermal delivery of the drug not only improves the drug's bioavailability but also maintains the concentration of the drug in the plasma without increasing the frequency of the drug dosage. Transdermal film formulations were developed using sodium alginate (SA) and lignosulphonic acid (LS) as the matrix and PEG-400 or Glycerine (Gly) as the plasticizers. Various physiochemical characteristic evaluations of the formulated films were conducted, revealing that the formulation with Glycerine as the plasticizer had a smooth surface and was flexible. It was observed that this formulation had the highest moisture uptake capacity and the lowest moisture loss capacity when compared with the other two formulations. It was also observed that the barium chloride cross-linked formulation had a higher swelling index when compared with calcium chloride cross-linked films. The surface pH of all the formulations was monitored to be around 7.5. In the in vitro release studies, the cross-linked films showed a controlled release over 36 h compared with the non-cross-linked films. Based on the observations and results, the cross-linked film formulation showed a better-controlled release of the drug and could potentially increase its bioavailability. TGA analysis of the polymeric mixture demonstrated the thermal stability of the SA blends, which enhanced the flexibility of the SALS blend with Glycerine. XRD of samples confirmed the amorphous nature of SALS blends with Gly, which influences the flexibility of the blend. The blends are further investigated for morphology using SEM to test their compatibility with the drug.

Formation of phenolic compound-loaded zein films at the air–liquid interface and their controlled release profiles: Effects of the polarity of phenolic compounds

Polyphenols are frequently utilized antioxidants in active packaging and anti-immflamotary bioactives in tissue engineering. Herein, we introduced a novel method for the rapid (<5 s) fabrication of interfacial self-assembled zein films (ZF) at the air–water interface. Polyphenols with different partition coeffient (Log P), namely, curcumin, resveratrol, and quercetin, were simultaneously loaded during the laterally occurred self-assembly process of zein molecules, respectively. Efficient loading and smart regulation over the physical distribution, intramolecule interaction and release profile in ZF were achieved. The main zein-polyphenol interactions exhibited hydrogen bonding and hydrophobic interactions that modulated the surface micromorphology of ZF and the release kinetics of different polyphenols. The log P of polyphenols affected the strength of the interaction of zein molecules, which in turn influenced the sustained release properties of polyphenols. This “bottom-up” strategy offers a novel way to rapidly incorporate and delicate control over the release of polyphenols.

Formulation and Evaluation of Pravastatin Sodium-Loaded PLGA Nanoparticles: In vitro-in vivo Studies Assessment.

Pravastatin sodium (PVS) is a hypolipidemic drug which suffers from extensive first-pass metabolism and short half-life. Poly(d,l-lactide-co-glycolide) (PLGA) is considered a promising carrier to improve its hypolipidemic and hepatoprotective activities. PVS-loaded PLGA nanoparticles (PVS-PLGA-NPs) were prepared by double emulsion method using a full 32 factorial design. The in vitro release and the physical stability studies of the optimized PVS-PLGA-NPs (F5) were performed. Finally, both hypolipidemic and hepatoprotective activities of the optimized F5 NPs were studied and compared to PVS solution. All the studied physical parameters of the prepared NPs were found in the accepted range. The particle size (PS) ranged from 90 ± 0.125 nm to 179.33 ± 4.509 nm, the poly dispersity index (PDI) ranged from 0.121 ± 0.018 to 0.158 ± 0.014. The optimized NPs (F5) have the highest entrapment efficiency (EE%) (51.7 ± 5%), reasonable PS (168.4 ± 2.506 nm) as well as reasonable zeta potential (ZP) (-28.3 ± 1.18mv). Solid-state characterization indicated that PVS is well entrapped into NPs. All NPs have distinct spherical shape with smooth surface. The prepared NPs showed a controlled release profile. F5 showed good stability at 4 ± 2°C during the whole storage period of 3 months. In vivo study and histopathological examination indicated that F5 NPs showed significant increase in PVS hypolipidemic as well as hepatoprotective activity compared to PVS solution. The PVS-PLGA-NPs could be considered a promising model to evade the first-pass effect and showed improvement in the hypolipidemic and hepatoprotective activities compared to PVS solution.