Delayed Drug Release Research Articles

Rational Design of Metal-Organic Frameworks for Pancreatic Cancer Therapy: from Machine Learning Screening to In Vivo Efficacy.

Despite improvements in cancer survival rates, metastatic and surgery-resistant cancers, such as pancreatic cancer, remain challenging, with poor prognoses and limited treatment options. Enhancing drug bioavailability in tumors, while minimizing off-target effects, is crucial. Metal-organic frameworks (MOFs) have emerged as promising drug delivery vehicles owing to their high loading capacity, biocompatibility, and functional tunability. However, the vast chemical diversity of MOFs complicates the rational design of biocompatible materials. This study employed machine learning and molecular simulations to identify MOFs suitable for encapsulating gemcitabine, paclitaxel, and SN-38, and identified PCN-222 as an optimal candidate. Following drug loading, MOF formulations are improved for colloidal stability and biocompatibility. In vitro studies on pancreatic cancer cell lines have shown high biocompatibility, cellular internalization, and delayed drug release. Long-term stability tests demonstrated a consistent performance over 12 months. In vivo studies in pancreatic tumor-bearing mice revealed that paclitaxel-loaded PCN-222, particularly with a hydrogel for local administration, significantly reduced metastatic spread and tumor growth compared to the free drug. These findings underscore the potential of PCN-222 as an effective drug delivery system for the treatment of hard-to-treat cancers.

Development studies on the orodispersible freeze-dried platforms for lurasidone hydrochloride - Understanding the effect of amino acid additive and lyophilization stage.

In this study, lyophilizates with the second-class antipsychotic agent lurasidone hydrochloride were developed as orodispersible platforms to improve patients' adherence. The primary aim was to evaluate the effect of the amino acid additive (L-arginine, L-lysine, L-histidine) and the freeze-drying stage on the pharmaceutical performance of the designed formulations. The composition was initially optimized using an experimental design approach. The amino acids (in particular L-histidine) acted as dispersing agents, prevented drug aggregation and assured high drug content uniformity within the lyophilizate matrix. The freeze-drying stage reduced the particles dimensions which significantly increased solubility of lurasidone hydrochloride, and consequently, it's dissolution rate. The presence of L-arginine in lyophilizate composition balanced out sufficient compression strength with a rapid drug release. Despite the fact that L-lysine enhanced the mechanical strength, it also caused delayed drug release. Notably, L-histidine and L-arginine accelerated transport of lurasidone hydrochloride through the porcine buccal epithelium with approximately 100% and 50% increase in absorption, respectively, when compared to commercial reference drug. Overall, the designed lyophilizates containing L-histidine and L-arginine, hold promise as orodispersible platforms for improved performance of lurasidone hydrochloride.

Delaying Drug Release

Delaying Drug Release

Dynamic versus static testing and in vivo mechanical performance of poly(glycolide-trimethylene carbonate-ε-caprolactone) delayed release implants.

The manufacturing of millimeter-sized implants for delayed drug release presents several challenges. However, it allows for the encapsulation of a therapeutic agent within a single device, enabling precise control over factors such as geometry, polymer composition, and drug formulation. The relatively large size, however, means that when inserted into subcutaneous tissue the implants experience mechanical stresses that are not predicted by current in vitro methods consisting of incubation under static conditions. The absence of a suitable in vitro assay complicates the device development process, often resulting in unsuccessful preclinical testing. This study presents the fabrication of flexible implants of poly(glycolide-co-trimethylene carbonate-co-ε-caprolactone), in vitro degradation, and performance when implanted subcutenously in rats. Predicting the in vivo behaviour is addressed by the development of a scalable, high-throughput, cyclic flexural testing system. Flexural loading of the implant demonstrates a clear impact on loss in mechanical properties compared to static conditions in lipoprotein lipase. Under static conditions, a lag time of 60 days is observed before sustained release of the model dye. Conversely, the flexural loading assay results in early fracture by 20 days consistent with what is observed in the animal model. Decisively, this study emphasizes the importance of tailoring in vitro assays according to the dosage form and intended mode of administration. Implementation of a dynamic in vitro assay is invaluable to efficiently evaluate device viability and release kinetics and will, in turn, allow a more streamlined workflow for translation into preclinical models.

Antioxidative hydrogel based on hyaluronic acid/polyethylene glycol loaded with shikonin-coated flexible liposome and evaluation of its therapeutic effect on eczema

Eczema, a common skin condition, is gaining attention due to its increasing annual prevalence and severe influence on both bodily and mental health. Existing treatments for this disease often have significant side effects and safety concerns. Comfrey, a traditional Chinese herbal remedy, is commonly used to treat skin conditions. Shikonin, the primary active compound in comfrey, has demonstrated efficacy in treating eczema. Herein, a flexible liposome-containing SHI was dispersed in hydrogels based on hyaluronic acid (HA) and polyethylene glycol(PEG) for the treatment of eczema. The hydrogel performed well in delaying drug release. SHI-F-Gel demonstrated notable antioxidant properties, effectively eliminating over 80 % of free radicals. Compared to the SHI solution, SHI-F-Gel significantly increased drug skin retention by 312.9 %. In animal studies, SHI-F-Gel administration reduced epidermal thickness in the affected area by approximately 36.8 % and increased collagen deposition by 90.23 %. Additionally, SHI-F-Gel inhibited the expression of pro-inflammatory cytokines interleukin-4 (IL-4) and IL-17. This observed reduction in inflammation suggests that the treatment is effective. In conclusion, the flexible SHI-based liposome hydrogel demonstrates excellent adhesion and biocompatibility, making it a promising candidate for enhancing eczema treatment.

Design, Formulation, Evaluation and Statistical Optimization of Coated Floating Pulsatile Tablets for Modified Chronopharmacotherapy of Rheumatoid Arthritis

Objective: Rheumatoid arthritis is a condition that needs early morning medication according to biorhythms. Hence, the main aim of designing Chronomodulated Floating Pulsatile Tablets (CFPT) of opioid analgesic and to perform in vitro drug release, in vitro buoyancy for modified chronopharmacotherapy of rheumatoid arthritis. Methods: The formulation was designed with the immediate core covered with buoyant composition and followed by immediate release layer. The best formulations of core tablets were compression coated with Methocel K100M, Plantago Ovate Gum (POG), and Tamarindus gum (TG) to assign a suitable lag time for formulation as a preliminary trial. Further 32 factorial designs was utilized to study polymer and Sodium Bicarbonate (SB) composition, Statistical optimization was done on dependent parameters such as FLT, FD, %DR5H, and % DR10H. Results: In this chronomodulated formulation, immediate release layer and core tablets were optimized with formulation IF4 which contains sodium starch Glycolate and Cross Carmellose sodium 8%, and then in buoyant formulation, CFPT was optimized by DoE optimization showing FF9 exhibiting good floating behavior and lag time. FLT of 125 sec, FD of 10h, % DR5H of 15.24% and maximum drug release of 98.28% were obtained for formulation FF9. Conclusion: As the formulation showed immediate and delayed drug release in vitro and also showed in-vitro buoyancy, hence nighttime administration could be beneficial to reduce the rheumatoid arthritis complications in the early morning.

Interaction of 6-Thioguanine with Aluminum Metal-Organic Framework Assisted by Mechano-Chemistry, In Vitro Delayed Drug Release, and Time-Dependent Toxicity to Leukemia Cells.

6-thioguanine (6-TG) is an antimetabolite drug of purine structure, approved by the FDA for the treatment of acute myeloid lesukemia, and it is of interest in treating other diseases. The interaction of drugs with matrices is of interest to achieving a delayed, sustained, and local release. The interaction of 6-TG with an aluminum metal-organic framework (Al-MOF) DUT-4 is studied using a novel experimental approach, namely, mechano-chemistry by liquid-assisted grinding (LAG). The bonding of 6-TG to the DUT-4 matrix in the composite (6-TG)(DUT-4) was studied using ATR-FTIR spectroscopy and XRD. This interaction involves amino groups and C and N atoms of the heterocyclic ring of 6-TG, as well as the carboxylate COO- and (Al)O-H groups of the matrix, indicating the formation of the complex. Next, an in vitro delayed release of 6-TG was studied from composite powder versus pure 6-TG in phosphate buffered saline (PBS) at 37 °C. Herein, an automated drug dissolution apparatus with an autosampler was utilized, and the molar concentration of the released 6-TG was determined using an HPLC-UV analysis. Pure 6-TG shows a quick (<300 min) dissolution, while the composite gives the dissolution of non-bonded 6-TG, followed by a significantly (factor 6) slower release of the bonded drug. Each step of the release follows the kinetic pseudo-first-order rate law with distinct rate constants. Then, a pharmaceutical shaped body was prepared from the composite, and it yields a significantly delayed release of 6-TG for up to 10 days; a sustained release is observed with the 6-TG concentration being within the therapeutically relevant window. Finally, the composite shows a time-dependent (up to 9 days) stronger inhibition of leukemia MV-4-11 cell colonies than 6-TG.

New challenges in scar therapy: the novel scar therapy strategies based on nanotechnology.

The pathological mechanism of pathological scar is highly complex, encompassing the abnormalities of diverse cytokines, signaling pathways and regulatory factors. To discover more preferable scar treatment options, a variety of distinct approaches have been utilized clinically. Nevertheless, these treatments possess certain side effects and are inclined to relapse. Presently, pathological scar treatment remains a clinical conundrum, and there is an urgent demand for treatment methods that are safe, less traumatic and have lower recurrence rates. New drug delivery systems, novel therapeutic drugs and therapy strategies can enable drugs to permeate the skin effectively, decrease side effects, enhance drug efficacy and even achieve pain-free self-administration. Currently, novel nanotechnologies such as nanomicroneedles, photodynamics mediated by novel photosensitizers, bioelectrical stimulation and 3D printed dressings have been developed for the effective treatment of pathological scars. Additionally, innovative nanoscale fillers, including nano-fat and engineered exosomes, can serve as novel therapeutic agents for the efficient treatment of pathological scars. The intervention of nanomaterials can enhance drug absorption, stabilize and safeguard the active ingredients of drugs, delay or control drug release and enhance bioavailability. This article reviews these new treatment strategies for scar to explore novel approaches for efficient and safe for keloid treatment.

Advancing inflammatory skin disease therapy: Sustained tofacitinib release via electrospun fiber dressings

Inflammatory skin diseases are typically managed with semi-solid formulations such as creams and ointments. These treatments often fail to remain on the skin for long, as they can be easily wiped off by clothing, necessitating frequent reapplication throughout the day and resulting in poor patient adherence. Therefore, this study sought to fabricate an electrospun dressing as an alternative dosage form that provides a sustained release of the anti-inflammatory agent tofacitinib over three days. In this study, three types of electrospun fiber dressings – uniaxial, coaxial, and layer-by-layer – were produced and examined for their morphological, mechanical, and release characteristics. In addition to a comprehensive characterization, another objective was to analyze the drug permeation behavior from these fiber dressings on porcine skin, comparing their performance to that of a tofacitinib cream. The layer-by-layer system notably exhibited a delayed drug release, while the uniaxial and coaxial systems demonstrated an initial burst release. However, the permeation studies revealed no significant differences between these systems, underscoring the necessity of conducting such studies – a crucial aspect often overlooked in research on electrospun fiber dressings. Overall, this study highlights the potential of electrospun, drug-loaded dressings for the treatment of inflammatory skin diseases.

Encapsulation of Gemcitabine on Porphyrin Aluminum Metal-Organic Framework by Mechano-Chemistry, Delayed Drug Release and Cytotoxicity to Pancreatic Cancer PANC-1 Cells.

Gemcitabine is a widely used antimetabolite drug of pyrimidine structure, which can exist as a free-base molecular form (Gem). The encapsulated forms of medicinal drugs are of interest for delayed and local drug release. We utilized, for the first time, a novel approach of mechano-chemistry by liquid-assisted grinding (LAG) to encapsulate Gem on a "matrix" of porphyrin aluminum metal-organic framework Al-MOF-TCPPH2 (compound 2). The chemical bonding of Gem to compound 2 was studied by ATR-FTIR spectroscopy and powder XRD. The interaction involves the C=O group of Gem molecules, which indicates the formation of the encapsulation complex in the obtained composite. Further, the delayed release of Gem from the composite was studied to phosphate buffered saline (PBS) at 37 °C using an automated drug dissolution apparatus equipped with an autosampler. The concentration of the released drug was determined by HPLC-UV analysis. The composite shows delayed release of Gem due to the bonded form and constant concentration thereafter, while pure Gem shows quick dissolution in less than 45 min. Delayed release of Gem drug from the composite follows the kinetic pseudo-first-order rate law. Further, for the first time, the mechanism of delayed release of Gem was assessed by the variable stirring speed of drug release media, and kinetic rate constant k was found to decrease when stirring speed is decreased (diffusion control). Finally, the prolonged time scale of toxicity of Gem to pancreatic cancer PANC-1 cells was studied by continuous measurements of proliferation (growth) for 6 days, using the xCELLigence real-time cell analyzer (RTCA), for the composite vs. pure drug, and their differences indicate delayed drug release. Aluminum metal-organic frameworks are new and promising materials for the encapsulation of gemcitabine and related small-molecule antimetabolites for controlled delayed drug release and potential use in drug-eluting implants.

Modification of a Carboxymethyl Cellulose/Poly(vinyl alcohol) Hydrogel Film with Citric Acid and Glutaraldehyde Crosslink Agents to Enhance the Anti-Inflammatory Effectiveness of Triamcinolone Acetonide in Wound Healing.

Anti-inflammatory wound healing involves targeted drug delivery to the wound site using hydrogel materials to prolong drug effectiveness. In this work, hydrogel films were fabricated using carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) crosslinked with citric acid (CA) and glutaraldehyde (GA) at different concentrations. The crosslinker densities were optimized with various CA (2-10% w/v) and GA (1-5% v/v) concentrations. The optimized crosslink densities in the hydrogel exhibited additional functional group peaks in the FT-IR spectra at 1740 cm-1 for the C=O stretching of the ester linkage in CA and at 1060 cm-1 for the C-O-C stretching of the ether group in GA. Significantly, the internal porous structures of hydrogel composite films improved density, swelling capacities, solubility percentage reduction, and decreased water retention capacities with optimized crosslinker densities. Therefore, these hydrogel composite films were utilized as drug carriers for controlled drug release within 24 h during medical treatment. Moreover, the hydrogel films demonstrated increased triamcinolone acetonide (TAA) absorption with higher crosslinker density, resulting in delayed drug release and improved TAA efficiency in anti-inflammatory activity. As a result, the modified hydrogel showed the capability of being an alternative material with enhanced anti-inflammatory efficiency with hydrogel films.

In-situ monitoring of in vitro drug release processes in tablets using optical coherence tomography

Film-coated modified-release tablets are an important dosage form amenable to targeted, controlled, or delayed drug release in the specific region of the gastrointestinal (GI) tract. Depending on the film composition and interaction with the GI fluid, such coated products can modulate the local bioavailability, systemic absorption, protection as an enteric barrier, etc. Although the interaction of a dosage form with the surrounding dissolution medium is vital for the resulting release behavior, the underlying physicochemical phenomena at the film and core levels occurring during the drug release process have not yet been well described. In this work, we attempted to tackle this limitation by introducing a novel in vitro test based on optical coherence tomography (OCT) that allows an in-situ investigation of the sub-surface processes occurring during the drug release. Using a commercially available tablet based on osmotic-controlled release oral delivery systems (OROS), we demonstrated the performance of the presented prototype in terms of monitoring the membrane thickness and thickness variability, the surface roughness, the core swelling behavior, and the porosity of the core matrix throughout the in vitro drug release process from OROS. The superior spatial (micron scale) and temporal (less than 10 ms between the subsequent tomograms) resolution achieved in the proposed setup provides an improved understanding of the dynamics inside the microstructure at any given time during the dissolution procedure with the previously unattainable resolution, offering new opportunities for the design and testing of patient-centric dosage forms.

Antimicrobial liposomes-in-nanofiber wound dressings prepared by a green and sustainable wire-electrospinning set-up

Increasing prevalence of infected and chronic wounds demands improved therapy options. In this work an electrospun nanofiber dressing with liposomes is suggested, focusing on the dressing’s ability to support tissue regeneration and infection control. Chloramphenicol (CAM) was the chosen antibiotic, added to the nanofibers after first embedded in liposomes to maintain a sustained drug release. Nanofibers spun from five different polymer blends were tested, where pectin and polyethylene oxide (PEO) was identified as the most promising polymer blend, showing superior fiber formation and tensile strength. The wire-electrospinning setup (WES) was selected for its pilot-scale features, and water was applied as the only solvent for green electrospinning and to allow direct liposome incorporation. CAM-liposomes were added to Pectin-PEO nanofibers in the next step. Confocal imaging of rhodamine-labelled liposomes indicated intact liposomes in the fibers after electrospinning. This was supported by the observed in vitroCAM-release, showing that Pectin-PEO-nanofibers with CAM-liposomes had a delayed drug release compared to controls. Biological testing confirmed the antimicrobial efficacy of CAM and good biocompatibility of all CAM-nanofibers. The successful fiber formation and green production process with WES gives a promising outlook for industrial upscaling.

Self-Assembled PLGA-Pluronic F127 Microsphere for Sustained Drug Release for Osteoarthritis.

For many years, sustained-release drug delivery systems (SRDDS) have emerged as a featured topic in the pharmaceutical field. Particularly for chronic diseases, such as osteoarthritis, there is a lot of demand for SRDDS because of the long treatment period and repetitive medication administration. Thus, we developed an injectable PLGA-F127 microsphere (MS) that is capable of the in situ conversion to an implant. The microprecipitation method for PLGA-F127 MS was established, and the physicochemical stability of the products was confirmed. The microspheres were assembled into a single mass in 37 °C aqueous conditions and showed a remarkably delayed drug release profile. First, the release started with no significant initial burst and lagged for 60 days. After that, in the next 40 days, the remaining 75% of the drugs were constantly released until day 105. We expect that our PLGA-F127 MS could be employed to extend the release period of 2 months of medication to 4 months. This could be a valuable solution for developing novel SRDDS for local injections.

ESTIMATING THE RELEASE EFFECT ON BSC-I DRUG BY USING A COMBINATION OF METHYLCELLULOSE AND EUDRAGIT® S-100 POLYMERS TO FORMULATE MINI-FLOATING TABLETS

The purpose of the current research was to prepare a delayed-release system of mini-tablets (gastroprokinetic drug). The model drug (itopride hydrochloride) was formulated with the combination of methylcellulose (free-flowing agent) and Eudragit® S-100 (enteric coating agent) for delayed release. The research objective was to control the drug release in the stomach. The preparation of floating minitablets in three batches using different concentrations of polymers (methylcellulose in increasing order and Eudragit® S-100 remaining constant in two batches and the concentration decreased in the third batch) was utilized for the maintenance of the drug release pattern by evaluating the three batches for their weight variation, content uniformity, % drug release, thickness, hardness and friability tests. The selection of optimized formulation was based on the in vitro dissolution studies and floating lag time. As a result, Eudragit® S-100 showed a better-delayed release action. Formulation F2 gave better-delayed release (67.09 % for 360 minutes) and floating properties (1.34 minutes for lag time) in comparison to other batches i.e.; F1 and F3. The F3 results showed that the floating lag time (1.29 minutes) will decline, while methylcellulose concentration increases but Eudragit® S-100 concentration decreases, which reveals the enteric coating action of the Eudragit® S-100 polymer for delayed drug release in the studies.

Effect of Biodegradable Mifepristone Drug Delivery System on the Ultrastructure and Angiogenesis Related Factors of Adenomyosis Cells

The aim of this research aimed to analyze the effects of degradable mifepristone nano-drug delivery system (DDS) on the ultrastructure, proliferation, apoptosis, and angiogenesis of adenomyosis cells. Drug-loaded nanoparticles (DNPs) of poly lactic-co-glycolic acid (PLGA) were prepared. The particle size distribution and surface Zeta potential (SZP) of nanoparticles (NPs) were detected. The morphology of NPS was subjected to observation by transmission electron microscope (TEM). Adenomyosis lesion cells were cultured by tissue digestion method, and the cell morphology was observed and identified. The cells were divided into blank control (NC), mifepristone, and mifepristone/PLGA groups. The cell proliferation, ultrastructure, apoptosis, and the expression of Survivin, VEGFR1, and VEGFR2 were detected by MTT, TEM, flow cytometry (FC), and immuno-histochemistry, respectively. The results suggested that the average particle size of mifepristone/PLGA NPs was (185.6±12.9) nm, and the SZP was (−9.5±0.9) mV. It presented the characteristics of circularity, uniform distribution, and smooth surface under TEM. As against the raw drug mifepristone, the release time of mifepristone/PLGA NPs was prolonged, and the drug release rate reached 87.4% at 72 h. As against NC, the cell proliferation rate (CPR) was clearly decreased, the apoptosis rate (AR) was increased, and Survivin, VEGFR1, and VEGFR2 had a decrease in mifepristone and mifepristone/PLGA groups (P &lt;0.05). As against mifepristone group, the CPR was clearly decreased, the AR was increased, and Survivin, VEGFR1, and VEGFR2 had a decrease in mifepristone/PLGA group (P &lt;0.05). In conclusion, mifepristone PLGA DNPs were able to delay drug release. Mifepristone can inhibit angiogenesis and promote apoptosis of adenomyosis by affecting the expression of Survivin, VEGFR1, and VEGFR2, thus playing a role in the treatment of adenomyosis.

DEVELOPMENT, CHARACTERIZATION AND PHARMACOKINETIC EVALUATION OF OPTIMIZED VILDAGLIPTIN SUSTAINED RELEASE MATRIX TABLET USING BOX-BEHNKEN DESIGN

Objective: The principal objective of this research was to develop and optimize cost-effective sustained-release Vildagliptin (VLN) tablets using the wet granulation method. Methods: The tablets were prepared by the non-aqueous wet granulation method. A Box-Behnken design was used to study the effect of the independent variables, i.e., HPMC K100 M, Eudragit RSPO and PVP K30, on the dependent variables swelling index, in vitro drug release at 8 and 12 h. The drug's physiochemical properties were investigated using ultraviolet (UV), Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC). The hardness, thickness, weight variation, content uniformity, swelling index, and in vitro drug release study of the formulated tablets were all evaluated. The optimized formulation Opt-VLD-SR was evaluated for pharmacokinetic parameters like AUC, Cmax, tmax and MRT. Results: The FTIR and DSC studies confirmed that no interaction occurred between the drug, polymers and excipients. The crystalline nature of VLN remained unchanged in the optimised formulation tablet, according to DSC studies. With the optimal concentration of both polymers, formulation Opt-VLN delayed drug release for up to 12 h. The formulated Optimized Sustained-release tablets (Opt-VLD-SR) showed significantly lower Cmax±3.01ng/ml) than conventional IR tablets (256.17±8.02ng/ml). In the pharmacokinetic study, the MRT for Optimized-VLD-SR is (7.40h) showed a better result than the Vildagliptin IR marketed product (3.70 h.), which leads to higher bioavailability of Vildagliptin. Conclusion: Sustained release tablets of VLN with a combination of diffusion and erosion-controlled drug release mechanisms have been successfully developed.

Anti-oxidant and anti-inflammatory potential of different polymer-based mesalamine delayed-release granules in TNBS-induced ulcerative colitis in wistar rats

Ulcerative colitis (UC) is an inflammatory condition of colon characterized by severe damage to the innermost colon tissues. A number of studies described the use of medication delivery systems based on natural polymers like polysaccharides for the purpose of reaching the colon. In this research, polymer-based mesalamine delayed-release granules (DRGs) were tested for their antioxidant and anti-inflammatory efficacy against UC. Chitosan (C), pectin (P), and pectin-chitosan (PC) mesalamine (M) DRGs were prepared and characterized. Data revealed satisfactory compatibility, flow, packing properties, drug release pattern, and delayed drug release by DRGs. Wistar rats were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (100 mg/kg) via rectal administration. Mesalamine and mesalamine DRGs (50 mg/kg) were administered orally separately for 14 days. Biomarkers of oxidative stress, inflammation, hematological tests, colon profile, and histopathology were performed. The findings demonstrated the good efficacy of the polysaccharides in delivering mesalamine to colon. Mesalamine and mesalamine DRGs based on various polymers showed significant antioxidant and anti-inflammatory effects in rats with UC. Mesalamine granules significantly attenuated colon lipid peroxidation, nitrites, myeloperoxidase activity, and interleukin-1β levels, and improved anti-oxidants (GSH, SOD). Data showed upregulation of Nrf2 activity by mesalamine granules with CM-DRGs showing maximum effect. Mesalamine and different polymer-based mesalamine DRGs significantly attenuated TNBS-induced decline in body weight, ulcer severity, and colon damage. CM-DRGs showed the most pronounced ameliorative effect on colon and hematology parameters via anti-oxidant and anti-inflammatory activities. Chitosan can be used as a carrier for oral colon delivery of mesalamine in DRG formulation for enhanced therapeutic efficacy in UC.

Development and Characterization of Thiolated Cyclodextrin-Based Nanoparticles for Topical Delivery of Minoxidil.

The aim of this research was to prepare adhesive nanoparticles for the topical application of Minoxidil (MXD). Thiolated β-CDs were prepared via conjugation of cysteamine with oxidized CDs. MXD was encapsulated within thiolated and unmodified β-CDs. Ionic gelation method was used to prepare nanoparticles (Thio-NP and blank NP) of CDs with chitosan. Nanoparticles were analyzed for size and zetapotential. Inclusion complexes were characterized via FTIR. Drug dissolution studies were carried out. An in vitro adhesion study over human hair was performed. An in vivo skin irritation study was performed. Ex vivo drug uptake was evaluated by using a Franz diffusion cell. Thiolated β-CDs presented 1804.68 ± 25 μmol/g thiol groups and 902.34 ± 25 μmol/g disulfide bonds. Nanoparticles displayed particle sizes within a range of 231 ± 07 nm to 354 ± 13 nm. The zeta potential was in the range of -8.1 ± 02 mV, +16.0 ± 05 mV. FTIR analyses confirmed no interaction between the excipients and drug. Delayed drug release was observed from Thio-NP. Thio-NP retained over hair surfaces for a significantly longer time. Similarly, drug retention was significantly improved. Thio-NP displayed no irritation over rabbit skin. Owing to the above results, nanoparticles developed with MXD-loaded thiolated β-CDs might be a potential drug delivery system for topical scalp diseases.

Enteric-coating film effect on the delayed drug release of pantoprazole gastro-resistant generic tablets.

Background: Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the coating formulation may affect their ability to provide adequate protection. This study is the first to investigate the potential effects of coating materials on the protective functionality of enteric coating films for pantoprazole (PNZ) generic tablets after their recall from the market. Methods: A comparative analysis was conducted between generic and branded PNZ products, using pure drug powder for identification. The in vitro release of the drug was evaluated in different pH media. The study also utilized various analytical and thermal techniques, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and confocal Raman microscopy. Results: The in vitro assessment results revealed significant variations in the release profile for the generic product in acidic media at 120 min. DSC and TGA thermal profile analyses showed slight variation between the two products. XRD analysis exhibited a noticeable difference in peak intensity for the generic sample, while SEM revealed smaller particle sizes in the generic product. The obtained spectra profile for the generic product displayed significant variation in peaks and band intensity, possibly due to impurities. These findings suggest that the excipients used in the enteric coating film of the generic product may have affected its protective functionality, leading to premature drug release in acidic media. Additionally, the presence of polysorbate 80 (P-80) in the brand product might improve the properties of the enteric coating film due to its multi-functionality. Conclusions: In conclusion, the excipients used in the brand product demonstrated superior functionality in effectively protecting the drug molecule from acidic media through the enteric coating film, as compared to the generic version.