Assessments of in vitro and in vivo antineoplastic potentials of ß-sitosterol-loaded PEGylated niosomes against hepatocellular carcinoma.

ß-sitosterol (BS), a phytosterol, exhibits ameliorative effects on hepatocellular carcinoma (HCC) due to its antioxidant activities. However, its poor aqueous solubility and negotiated bioavailability and short elimination half-life is a huge limitation for its therapeutic applications. To overcome these two shortcomings, BS-loaded niosomes were made to via, film hydration method and process parameters were optimized using a three-factor Box-Behnken design. The optimized formulation (BSF) was further surface-modified with polyethylene glycol (PEG). The resulting niosomes (BSMF) have spherical shapes, particle sizes, 219.6 ± 1.98 nm with polydispersity index (PDI) and zeta potential of 0.078 ± 0.04 and -19.54 ± 0.19 mV, respectively. The drug loading, entrapment efficiency, and drug release at 24 h of the BSMF were found to be 16.72 ± 0.09%, 78.04 ± 0.92%, and 75.10 ± 3.06%, respectively. Moreover, BSMF showed significantly greater cytotoxic potentials on Hep G2 cells with an enhanced cellular uptake relative to pure BS and BSF. The BSMF also displayed potentially improved curative property of HCC in albino wistar rat. Thus, the BSMF could be one of the promising therapeutic modalities for HCC treatment in terms of targeting potential resulting in enhanced therapeutic efficacy.

Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies.

The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68±0.13µM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77±0.25µM and IC50: 12.59±0.21µM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74±0.09µM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52±0.62µM and IC50: 13.13±0.85µM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.

Mannose-Decorated Solid-Lipid Nanoparticles for Alveolar Macrophage Targeted Delivery of Rifampicin.

Alveolar macrophages play a vital role in a variety of lung diseases, including tuberculosis. Thus, alveolar macrophage targeted anti-tubercular drug delivery through nanocarriers could improve its therapeutic response against tuberculosis. The current study aimed at exploring the efficacy of glyceryl monostearate (GMS)-based solid-lipid nanoparticles (SLNs) and their mannose functionalized forms on the alveolar macrophage targeting ability of an anti-tubercular model drug, rifampicin (Rif). Rif-loaded SLNs were accomplished by the solvent diffusion method. These carriers with unimodal particle size distribution (~170 nm) were further surface-modified with mannose via Schiff-base reaction, leading to slight enhancement of particle diameter and a decline of drug loading capacity. The encapsulated Rif, which was molecularly dispersed within the matrices as indicated by their XRD patterns, was eluted in a sustained manner with an initial burst release effect. The uptake efficiency of mannose-modified SLNs was remarkably higher than that of corresponding native forms on murine macrophage Raw 264.7 cells and human lung adenocarcinoma A549 cells. Eventually, the mannose-modified SLNs showed a greater cytotoxicity on Raw 264.7 and A549 cells relative to their unmodified forms. Overall, our study demonstrated that mannose modification of SLNs had an influence on their uptake by alveolar macrophages, which could provide guidance for the future development of alveolar macrophage targeted nanoformulations.

Ferulic acid-g-tamarind gum/guar gum based in situ gel-forming powders as wound dressings.

The current research endeavour aimed to synthesize ferulic acid grafted tamarind gum/guar gum (FA-g-TG/GG) based powders as wound dressings, which could form in situ gels upon contact with wound exudates. In this context, variable amounts of FA were initially grafted with TG via the Steglich esterification reaction protocol and the resulting conjugates were subsequently amalgamated with GG and lyophilized to produce dry powders (F-1 - -F-3) with average particle size within 5.10-5.54 µm and average angle of repose ∼30°. These powders were structurally characterized with 1H NMR, FTIR, DSC, TGA, XRD and SEM analyses. Pristine TG, FA-g-TG and FA-g-TG/GG powders (F-2) revealed their distinct morphological structures and variable negative zeta potential values (-11.06 mV-25.50 mV). Among various formulation (F-1-F-3), F-2 demonstrated an acceptable powder-to-gel conversion time (within 20 min), suitable water vapour transmission rates (WVTR, 2564.94 ± 32.47 g/m2/day) and excellent water retention abilities and swelling profiles (4559.00 ± 41.57 %) in wound fluid. The powders were cytocompatible and conferred antioxidant activities. The powders also displayed fibroblast cell proliferation, migration and adhesion properties, implying their wound-healing potentials. Thus, the developed in situ gel-forming powders could be employed as promising dressings for wound management.

Pulmonary fibroblast-specific delivery of siRNA exploiting exosomes-based nanoscaffolds for IPF treatment.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that leads to interstitial inflammation, lung damage, and eventually life-threatening complications. Among various pathologic factors, Smad4 is a pivotal molecule involved in the progression and exacerbation of IPF. It mediates nuclear transfer of Smad2/Smad3 complexes and initiates the transcription of fibrosis-promoting genes. Thus, the inhibition of Smad4 expression in pulmonary fibroblasts by small interfering RNAs (siRNAs) might be a promising therapeutic strategy for IPF. Herein, we engineered exosome membranes (EM) by cationic lipid (i.e., DOTAP) to load siRNAs against Smad4 (DOTAP/siSmad4@EM), and investigated their specific delivery to pulmonary fibroblasts for treating IPF in a mouse model via pulmonary administration. As reference nanoscaffolds, undecorated DOTAP/siSmad4 complexes (lipoplexes, consisting of cationic lipid DOTAP and siRNAs) and siSmad4-loaded lipid nanoparticles (DOTAP/siSmad4@lipo, consisting of lipoplexes fused with DPPC-Chol liposomes) were also prepared. The results showed that DOTAP/siSmad4@EM exhibited a higher cellular uptake and gene silencing efficacies in mouse pulmonary fibroblasts (viz., MLg2908) as compared to the two reference nanoscaffolds. Furthermore, the outcomes of the in vivo experiments illustrated that DOTAP/siSmad4@EM could significantly down-regulate the Smad4 expression with augmented anti-fibrosis efficiency. Additionally, the DOTAP/siSmad4@EM conferred excellent biocompatibility with low cytokine levels in bronchoalveolar lavage fluid and proinflammatory responses in the pulmonary area. Taken together, the outcomes of our investigation imply that specific inhibition of Smad4 expression in pulmonary fibroblasts by pulmonary administrated DOTAP/siSmad4@EM is a promising therapeutic strategy for IPF, which could safely and effectively deliver siRNA drugs to the targeted site of action.

Co-spray dried inhalable composite powders of ciprofloxacin and alginate oligosaccharide as anti-biofilm therapy.

The treatment of chronic respiratory infections caused by biofilm formation are extremely challenging owing to poor drug penetration into the complex biofilm structure and high drug resistance. Local delivery of an antibiotic together with a non-antibiotic adjuvant to the lungs could often enhance the therapeutic responses by targeting different bacterial growth pathways and minimizing drug resistance. In this study, we designed new inhalable dry powders containing ciprofloxacin (CIP) and OligoG (Oli, a low-molecular-weight alginate oligosaccharide impairing the mucoid biofilms by interacting with their cationic ions) to combat respiratory bacterial biofilm infections. The resulting powders were characterized with respect to their morphology, solid-state property, surface chemistry, moisture sorption behavior, and dissolution rate. The aerosol performance and storage stability of the dry powders were also evaluated. The results showed that inhalable dry powders composed of CIP and Oli could be readily accomplished via the wet milling and spray drying process. Upon the storage under 20 ± 2 °C/20 ± 2 % relative humidity (RH) for one month, there was no significant change in the in vitro aerosol performances of the dry powders. In contrast, the dry powders became non-inhalable following the storage at 20 ± 2 °C/53 ± 2 % RH for one month due to the hygroscopic nature of Oli, which could be largely prevented by incorporation of leucine. Collectively, this study suggests that the newly developed co-spray-dried powders composed of CIP and Oli might represent a promising and alternative treatment strategy against respiratory bacterial biofilm infections.

Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones.

In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value=42.63 µM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions.

Recent advances in pH/enzyme-responsive polysaccharide-small-molecule drug conjugates as nanotherapeutics.

Now-a-days, the polysaccharides are extensively employed for the delivery of small-molecule drugs ascribed to their excellent biocompatibility, biodegradability and modifiability. An array of drug molecules is often chemically conjugated with different polysaccharides to augment their bio-performances. As compared to their therapeutic precursors, these conjugates could typically demonstrate an improved intrinsic solubility, stability, bioavailability and pharmacokinetic profiles of the drugs. In current years, various stimuli-responsive particularly pH and enzyme-sensitive linkers or pendants are also exploited to integrate the drug molecules into the polysaccharide backbone. The resulting conjugates could experience a rapid molecular conformational change upon exposure to the microenvironmental pH and enzyme changes of the diseased states, triggering the release of the bioactive cargos at the targeted sites and eventually minimize the systemic side effects. Herein, the recent advances in pH and enzyme -responsive polysaccharide-drug conjugates and their therapeutic benefits are systematically reviewed, following a brief description on the conjugation chemistry of the polysaccharides and drug molecules. The challenges and future perspectives of these conjugates are also precisely discussed.

Engineering Transferrin-Decorated Pullulan-Based Prodrug Nanoparticles for Redox Responsive Paclitaxel Delivery to Metastatic Lung Cancer Cells.

Paclitaxel (PTX) remains a cornerstone in the treatment of locally advanced and metastatic lung cancer. To improve its therapeutic indices against lung cancer, novel redox-sensitive pullulan/PTX-based prodrug NPs (PULL-SS-PTX NPs) were accomplished, which were further surface-decorated with transferrin (TF), a cancer cell-targeting ligand, to afford TF-PULL-SS-PTX NPs. These prodrug NPs (drug content, >37% and average size, 134-163 nm) rapidly dismantled their self-assembled architecture upon exposure to simulated reducing conditions, causing a triggered drug release as compared to the control scaffold (PULL-CC-PTX NPs). These scaffolds also evidenced outstanding colloidal stability, cellular uptake efficiency, and discriminating cytotoxicity between the cancer and healthy cells. Intravenously delivered redox-sensitive NPs exhibited improved tumor-suppressing properties as compared to the control nanovesicles (PULL-CC-PTX NPs) in a B16-F10 melanoma lung metastasis mice model. The targeting efficiency and associated augmented anticancer potentials of TF-PULL-SS-PTX NPs relative to TF-free redox-responsive NPs and Taxol intravenous injection were also established on the transferrin receptor (TFR) overexpressed Lewis lung carcinoma (LLC-luc) cell-bearing mice model. Moreover, the TF-functionalized scaffold displayed a reduced systemic toxicity compared to that of Taxol intravenous injection. Overall, the proposed TF-decorated prodrug NPs could be a promising nanomedicine for intracellular PTX delivery against metastatic lung cancer.

20(R)-ginsenoside Rg3-loaded polyurethane/marine polysaccharide based nanofiber dressings improved burn wound healing potentials.

The management of deep burn injuries is extremely challenging, ascribed to their delayed wound healing rate, susceptibility for bacterial infections, pain, and increased risk of hypertrophic scarring. In our current investigation, a series of composite nanofiber dressings (NFDs) based on polyurethane (PU) and marine polysaccharides (i.e., hydroxypropyl trimethyl ammonium chloride chitosan, HACC and sodium alginate, SA) were accomplished by electrospinning and freeze-drying protocols. The 20(R)-ginsenoside Rg3 (Rg3) was further loaded into these NFDs to inhibit the formation of excessive wound scars. The PU/HACC/SA/Rg3 dressings showed a sandwich-like structure. The Rg3 was encapsulated in the middle layers of these NFDs and slowly released over 30 days. The PU/HACC/SA and PU/HACC/SA/Rg3 composite dressings demonstrated superior wound healing potentials over other NFDs. These dressings also displayed favorable cytocompatibility with keratinocytes and fibroblasts and could dramatically accelerate epidermal wound closure rate following 21 days of the treatment of a deep burn wound animal model. Interestingly, the PU/HACC/SA/Rg3 obviously reduced the excessive scar formation, with a collagen type I/III ratio closer to the normal skin. Overall, this study represented PU/HACC/SA/Rg3 as a promising multifunctional wound dressing, which promoted the regeneration of burn skins and attenuated scar formation.

Unleashing the healing potential: Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery.

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management. In this study, a greater efficacy in burn wound healing and the associated mechanisms of α-lactalbumin (ALA) based electrospun nanofibrous scaffolds (ENs) as compared to other regenerative protein scaffolds were established. Bovine serum albumin (BSA), collagen type I (COL), lysozyme (LZM) and ALA were separately blended with poly(ε-caprolactone) (PCL) to fabricate four different composite ENs (LZM/PCL, BSA/PCL, COL/PCL and ALA/PCL ENs). The hydrophilic composite scaffolds exhibited an enhanced wettability and variable mechanical properties. The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs. As compared to PCL ENs and other composite scaffolds, the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen spongeⓇ on third-degree burn model. The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites. Collectively, this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.

Airway epithelial cell-specific delivery of lipid nanoparticles loading siRNA for asthma treatment.

With specific and inherent mRNA cleaving activity, small interfering RNA (siRNA) has been deemed promising therapeutics to reduce the exacerbation rate of asthma by inhibiting the expression and release of proinflammatory cytokines from airway epithelial cells (AECs). To exert the therapeutic effects of siRNA drugs, nano-formulations with high efficiency and safety are required to deliver these nucleic acids to the target cells. Herein, we exploited novel inhaled lipid nanoparticles (LNPs) targeting intercellular adhesion molecule-1 (ICAM-1) receptors on the apical side of AECs. This delivery system is meant to enhance the specific delivery efficiency of siRNA in AECs to prevent the expression of proinflammatory cytokines in AECs and the concomitant symptoms in parallel. A cyclic peptide that resembles part of the capsid protein of rhinovirus and binds to ICAM-1 receptors was initially conjugated with cholesterol and subsequently assembled with ionizable cationic lipids to form the LNPs (Pep-LNPs) loaded with siRNA against thymic stromal lymphopoietin (TSLP siRNA). The obtained Pep-LNPs were subjected to thorough characterization and evaluations in vitro and in vivo. Pep-LNPs significantly enhanced cellular uptake and gene silencing efficiency in human epithelial cells expressing ICAM-1 in vitro, exhibited AEC-specific delivery and improved the gene silencing effect in ovalbumin-challenged asthmatic mice after pulmonary administration. More importantly, Pep-LNPs remarkably downregulated the expression of TSLP in AECs, effectively alleviated inflammatory cell infiltration, and reduced the secretion of other proinflammatory cytokines, including IL-4 and IL-13, as well as mucus production in asthmatic mice. This study demonstrates that Pep-LNPs are safe and efficient to deliver siRNA drugs to asthmatic AECs and could potentially alleviate allergic asthma by inhibiting the overexpression of proinflammatory cytokines in the airway.

Mechanistic exploration of the activities of poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid against hepatocellular carcinoma at cellular and molecular levels.

The effectiveness of betulinic acid (B) and PLGA loaded nanoparticles of B (Bnp) against hepatocellular carcinoma (HCC) was established and reported earlier. In continuation of our previous report, the present study described the molecular mechanisms of their antineoplastic responses. In this context, the antineoplastic properties of both B and Bnp were evaluated on DEN-induced HCC rat model. The quantitative real-time polymerase chain reaction and western blot analyses revealed that HCC was developed through lower expressions of e-NOS, BAX, BAD, Cyt C and higher expressions of i-NOS, Bcl-xl, Bcl-2. B and Bnp normalised the expressions of these apoptogenic markers. Particularly, both activated i-NOS and e-NOS mediated Bcl-2 family proteins→CytC→Caspase 3 and 9 signalling cascades. The 1H-NMR-based metabolomics study also demonstrated that the perturbed metabolites in DEN-induced rat serum restored to the normal level following both treatments. Moreover, the antineoplastic potential of Bnp was found to be comparable with the marketed product, 5-flurouracil.

Combination and nanotechnology based pharmaceutical strategies for combating respiratory bacterial biofilm infections.

Respiratory infections are one of the major global health problems. Among them, chronic respiratory infections caused by biofilm formation are difficult to treat because of both drug tolerance and poor drug penetration into the complex biofilm structure. A major part of the current research on combating respiratory biofilm infections have been focused on destroying the matrix of extracellular polymeric substance and eDNA of the biofilm or promoting the penetration of antibiotics through the extracellular polymeric substance via delivery technologies in order to kill the bacteria inside. There are also experimental data showing that certain inhaled antibiotics with simple formulations can effectively penetrate EPS to kill surficially located bacteria and centrally located dormant bacteria or persisters. This article aims to review recent advances in the pharmaceutical strategies for combating respiratory biofilm infections with a focus on nanotechnology-based drug delivery approaches. The formation and characteristics of bacterial biofilm infections in the airway mucus are presented, which is followed by a brief review on the current clinical approaches to treat respiratory biofilm infections by surgical removal and antimicrobial therapy, and also the emerging clinical treatment approaches. The current combination of antibiotics and non-antibiotic adjuvants to combat respiratory biofilm infections are also discussed.

Particle engineering principles and technologies for pharmaceutical biologics.

The global market of pharmaceutical biologics has expanded significantly during the last few decades. Currently, pharmaceutical biologic products constitute an indispensable part of the modern medicines. Most pharmaceutical biologic products are injections either in the forms of solutions or lyophilized powders because of their low oral bioavailability. There are certain pharmaceutical biologic entities formulated into particulate delivery systems for the administration via non-invasive routes or to achieve prolonged pharmaceutical actions to reduce the frequency of injections. It has been well documented that the design of nano- and microparticles via various particle engineering technologies could render pharmaceutical biologics with certain benefits including improved stability, enhanced intracellular uptake, prolonged pharmacological effect, enhanced bioavailability, reduced side effects, and improved patient compliance. Herein, we review the principles of the particle engineering technologies based on bottom-up approach and present the important formulation and process parameters that influence the critical quality attributes with some mathematical models. Subsequently, various nano- and microparticle engineering technologies used to formulate or process pharmaceutical biologic entities are reviewed. Lastly, an array of commercialized products of pharmaceutical biologics accomplished based on various particle engineering technologies are presented and the challenges in the development of particulate delivery systems for pharmaceutical biologics are discussed.

Etherified pullulan-polyethylenimine based nanoscaffolds improved chemosensitivity of erlotinib on hypoxic cancer cells.

The current research endeavor aimed to accomplish hypoxia-responsive polyethyleneimine-conjugated carboxymethyl pullulan-based co-polymer (CMP-HA-NI-PEI-NBA) bearing nitroaromatic subunits to efficiently deliver erlotinib (ERL) to reverse its hypoxia-induced resistance in cancer cells. As compared to a control co-polymer (CMP-HA-MI-PEI-BA) devoid of hypoxia-sensitive moieties, this scaffold demonstrated a hypochromic shift in the UV spectra and rapid dismantling of its self-assembled architecture upon exposure to simulated hypoxic condition. The hypoxia-responsive co-polymer encapsulated ERL with desirable loading capacity (DEE, 63.05 ± 2.59%), causing attenuated drug crystallinity. The drug release rate of the scaffold under reducing condition was faster relative to that of non-reducing environment. Their cellular uptake occurred through an energy-dependent endocytic process, which could exploit its caveolae/lipid raft-mediated internalization pathway. The ERL-loaded scaffolds more efficiently induced apoptosis and suppressed the proliferation of drug-resistant hypoxic HeLa cells than the pristine ERL. Hence, this study presented a promising drug delivery nanoplatform to overcome hypoxia-evoked ERL resistance.

Hypoxia-responsive pullulan-based nanoparticles as erlotinib carriers.

A hypoxia-responsive pullulan-based co-polymer was developed to assess its efficacy to deliver erlotinib (ERL) to the cervical cancer cells. Upon exposure to hypoxic condition, the synthesized and structurally characterized co-polymer i.e. succinyl pullulan-g-6-(2-nitroimidazole) hexylamine (Pull-SA-HA-NI) exhibited a hypochromic shift in the UV spectra and alteration in its self-assembled structures as compared to the control co-polymer, succinyl pullulan-g-hexylamine (Pull-SA-HA). Its corresponding ERL-loaded nanoparticles (NPs) displayed an attenuated crystallinity of pure ERL with excellent drug-trapping capacity (DEE, 94.23 ± 1.36%) and acceptable zeta potential (+39.21 ± 1.09 mV) and diameter (84.10 ± 2.10 nm) values. These also evidenced a faster drug release profile under hypoxic condition relative to the normoxic condition. The cellular internalization of the NPs was mediated through the energy-dependent endocytic process, which could utilize its multiple pathways (i.e., macropinocytosis, clathrin- and caveolae-mediated endocytosis). The ERL-loaded NPs suppressed HeLa cell proliferation and induced apoptosis more efficiently than the pristine drug.

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines.

Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma, chronic obstructive pulmonary diseases and respiratory infections, and systemic diseases such as diabetes. Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit. The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration, but also enhance the clinical benefits to the patients with improved therapeutic outcomes. This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines. It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure, which is followed by recent advances in various strategies to overcome these barriers. Finally, the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.

Electro-hydrodynamic assisted synthesis of lecithin-stabilized peppermint oil-loaded alginate microbeads for intestinal drug delivery.

Peppermint oil (PO) is the most prominent oil using in pharmaceutical formulations with its significant therapeutic value. In this sense, this oil is attracting considerable attention from the scientific community due to its traditional therapeutic claim, biological and pharmacological potential in recent research. An organic solvent-free and environment-friendly electrohydrodynamic assisted (EHDA) technique was employed to prepared PO-loaded alginate microbeads. The current study deals with the development, optimization, in vitro characterization, in vivo gastrointestinal tract drug distribution and ex-vivo mucoadhesive properties, antioxidant, and anti-inflammatory effects of PO-loaded alginate microbeads. The optimization results indicated the voltage and flow rate have a significant influence on microbeads size and sphericity factor and encapsulation efficiency. All these optimized microbeads showed a better drug release profile in simulated intestinal fluid (pH 6.8) at 2 h. However, a minor release was found in acidic media (pH 1.2) at 2 h. The optimized formulation showed excellent mucoadhesive properties in ex-vivo and good swelling characterization in intestine media. The microbeads were found to be well distributed in various parts of the intestine in in vivo study. PO-loaded alginate microbeads similarly showed potential antioxidant effects with drug release. The formulation exhibited possible improvement of irritable bowel syndrome (IBS) in MO-induced rats. It significantly suppressed proinflammatory cytokines, i.e., interleukin- IL-1ß, and upregulated anti-inflammatory cytokine expression, i.e., IL-10. It would be a promising approach for targeted drug release after oral administration and could be considered an anti-inflammatory therapeutic strategy for treating IBS.

Chemosensitivity assessments of curdlan-doped smart nanocomposites containing erlotinib HCl.

Curdlan (CN)-doped montmorillonite/poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide) [CN/MT/P(NIPA-co-MBA)] smart nanocomposites (NCs) were developed for efficient erlotinib HCl (ERL) delivery to lung cancer cells. The placebo NCs demonstrated excellent biodegradability, pH/thermo-responsive swelling profiles and declined molar mass (M¯c) between the crosslinks with increasing temperature. The XRD, FTIR, DSC, TGA, and SEM analyses revealed the architectural chemistry of these NC scaffolds. The NCs loaded with ERL (F-1-F-3) displayed acceptable diameter (734-1120 nm) and zeta potential (+1.16 to -11.17 mV), outstanding drug entrapping capability (DEE, 78-99%) and sustained biphasic ERL elution patterns (Q8h, 53-91%). The ERL release kinetics of the optimal matrices (F-3) obeyed Higuchi model and their transport occurred through anomalous diffusion. The mucin adsorption behaviour of these matrices followed Freudlich isotherms. As compared to pure ERL, the formulation (F-3) displayed an improved anti-proliferative potential and induced apoptosis more effectively on A549 cells. Thus, the CN-doped smart NCs could be utilized as promising drug-cargoes for lung cancer therapy.