Drug Release Mechanism Research Articles

Solid-in-oil nanodispersion as a novel topical transdermal delivery to enhance stability and skin permeation and retention of hydrophilic drugs l-ascorbic acid

l-ascorbic acid （Vitamin C, VC） is the most abundant antioxidant in human skin. But its poor penetration into the skin and unstability limit the application. The aim of the study was to promote the topical skin permeation and retention of VC, increase the stability as well as effectiveness by a novel solid in oil nanodispersion. In the nanodispersions system, nano-sized particles of hydrophilic molecules are dispersed in an oil vehicle with the assistance of hydrophobic surfactants. The optimized formula composed of O170 and S1570 (12.5:1, w/w) showed high EE% of 98% and good stability. FTIR analysis confirmed that there may be hydrogen bond between VC and surfactants. The results of DSC, and XRD revealed that the drug was successfully encapsulated in the surfactants, which maintained the stability of drug. By analyzing and fitting the release data in vitro, the drug release mechanism of SONDs was predicted as a multi-dynamic model. Skin permeation of VC was improved 3.43-fold for SONDs compared with VC aqueous solution, highlighting that the lipophilicity and nano size of the carrier more easily penetrated into the skin. Finally, the photoaging study revealed that topical application of VC-SONDs provided the highest skin protection compared UV and VC aqueous solution treated group which was evident by the normal thick epidermal morphology, no obvious melanocytes and the densely arranged dermal elastic fibers. These results demonstrated that the solid-in-oil nanodispersions may be a potential transdermal delivery system for hydrophilic bioactive ingredients.

Microneedle-mediated treatment for superficial tumors by combining multiple strategies.

Superficial tumors are still challenging to overcome due to the high risk and toxicity of surgery and conventional chemotherapy. Microneedles (MNs) are widely used in the treatment of superficial skin tumors (SST) due to the high penetration rate of the stratum corneum (SC), excellent biocompatibility, simple preparation process, high patient compliance, and minimal invasion. Most importantly, MNs can provide not only efficient and rarely painful delivery carriers, but also combine multi-model strategies with photothermal therapy (PTT), immunotherapy, and gene therapy for synergistic efficacy. To promote an in-depth understanding of their superiorities, this paper systematically summarized the latest application progress of MNs in the treatment of SST by delivering various types of photosensitizers, immune signal molecules, genes, and chemotherapy drugs. Just as important, the advantages, limitations, and drug release mechanisms of MNs based on different materials are introduced in the paper. In addition, the application of MN technology to clinical practice is the ultimate goal of all the work. The obstacles and possible difficulties in expanding the production of MNs and achieving clinical transformation are briefly discussed in this paper. To be anticipated, our work will provide new insights into the precise and rarely painful treatment of SST in the future.

Characteristics of Mitomycin C-Loaded Peptide Hydrogel In Vitro and Antiscarring Effects in Rat Ocular Injury Model.

Purpose: To investigate the characteristics of sustained drug release systems established by an arginine-glycine-aspartic acid (RGD) peptide hydrogel and mitomycin C (MMC) in vitro, and verify their antiscar effects in rat ocular injury model. Methods: Low, medium, and high loading doses of MMC were added to 5 mL 0.25%, 0.5%, and 1% wt RGD peptide hydrogel, respectively, to prepare 9 ratios of MMC-RGD systems. Drug release characteristics of the systems in phosphate-buffered saline solution were investigated by plotting the drug release curves and fitting them with mathematical models in OriginPro8.0 software. Appropriate ratios of MMC-RGD systems were selected as treatment in rat ocular injury model. Scar formation was observed by Masson staining and immunohistochemical staining with alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Results: Nine ratios of MMC-RGD systems could release drug slowly. The maximum drug release proportions of all systems were >80%, and the time to maximum release proportions statistically prolonged with the increase of drug loading. Fitting with mathematical models indicated that the mechanisms of drug release were mainly Fick diffusion at early stage and Anomalous Transport at later stage. Systems of 1% wt RGD hydrogel were evaluated in animal experiments, which could inhibit hyperplasia of collagen and expression of α-SMA and FN. Conclusions: The RGD peptide hydrogel could be used as the carrier of MMC to establish sustained drug release system, which could inhibit scar formation after rat's ocular injury.

Self-assembly and drug release mechanisms of mechano-responsive and antibacterial F127-Rif hydrogels

Self-assembly and drug release mechanisms of mechano-responsive and antibacterial F127-Rif hydrogels

Effectiveness of temperature and preparation method on stability kinetic of Curcumin nanodispersion: Cytotoxicity and in vitro release assessment

Curcumin is a natural and non-polar pigment with unique properties such as antioxidant activity that has been widely utilized in food and pharmaceutical formulations. In this study, solvent displacement and subcritical water methods were used to prepare Curcumin nanodispersions. The influences of the method and storage temperature were evaluated on physical and chemical stability of the prepared nanodispersions. Obtained results indicated that prepared transparent nanodispersions maintained their physical and chemical stability at 4 and 25 °C for 4 months. The results also showed that the prepared nanodispersions using subcritical water (temperature of 120 °C and pressure of 1.5 atm for 2 h) had a higher stability (minimum changes in the particle size) and less Curcumin loss (0.36%). Release of Curcumin from prepared nanodispersions was also evaluated at different pH values (1.2, 5.4, and 7.4) and the results indicated that its release rate was higher in pH values ranging 5 to 7. Kinetic study showed that release of Curcumin from dialysis bag was controlled by diffusion at pH value of 7.4 with a high constant rate. The viability percentage of HT-29 cells against pure Curcumin and Curcumin nanodispersions prepared using solvent displacement and subcritical water methods for 72 h incubation were 94, 30 and 18%, respectively. Moreover, In drug delivery systems, mathematical modeling and simulation play an important role in elucidating important drug release mechanisms; therefore, the results of experimental data of diffusion rate were compared with those obtained from simulation, and a good agreement was found.

K-Carrageenan/sericin-based multiparticulate systems: A novel gastro-resistant polymer matrix for indomethacin delivery

This study aimed to develop a natural and multiparticulate carrier of k-carrageenan (k-Car) and sericin (Ser) for encapsulation of indomethacin (IND) in order to minimize gastrointestinal effects caused by immediate-release. Increasing the amount of IND in the formulations subtly reduced the entrapment efficiency (EE) and drug loading (DL) due to matrix saturation. Sericin was essential to improve EE and DL when compared to pure k-Car (EE > 90 % and DL > 47 %) with suitable particle sizes (1.3461 ± 0.1891–1.7213 ± 0.1586 mm). The incorporation and integrity of IND in the particles were confirmed by analytical techniques of HPLC, XRD, FTIR, and SEM. Additionally, the k-Car/Ser matrix was pH-responsive with low IND release at pH 1.2 and extended-release at pH 6.8. The Weibull model had an adequate fit to the experimental data with R2aju 0.950.99 and AIC 82.4–24.9, with curves in parabolic profile (b < 1) and indicative of a controlled drug-release mechanism by diffusion. Besides, k-Car/Ser/IND and placebo were not cytotoxic (cell viability > 85 % at 150–600 μM) for the Caco-2 cell line. Therefore, the polymeric matrix is gastro-resistant, stable, and biocompatible to carry indomethacin and deliver it to the intestinal environment.

Hybrid Hydrogels for Neomycin Delivery: Synergistic Effects of Natural/Synthetic Polymers and Proteins.

This paper reports new physical hydrogels obtained by the freezing/thawing method. They include pullulan (PULL) and poly(vinyl alcohol) (PVA) as polymers, bovine serum albumin (BSA) as protein, and a tripeptide, reduced glutathione (GSH). In addition, a sample containing PULL/PVA and lysozyme was obtained in similar conditions. SEM analysis evidenced the formation of networks with porous structure. The average pore size was found to be between 15.7 μm and 24.5 μm. All samples exhibited viscoelastic behavior typical to networks, the hydrogel strength being influenced by the protein content. Infrared spectroscopy analysis revealed the presence of intermolecular hydrogen bonds and hydrophobic interactions (more pronounced for BSA content between 30% and 70%). The swelling kinetics investigated in buffer solution (pH = 7.4) at 37 °C evidenced a quasi-Fickian diffusion for all samples. The hydrogels were loaded with neomycin trisulfate salt hydrate (taken as a model drug), and the optimum formulations (samples containing 10-30% BSA or 2% lysozyme) proved a sustained drug release over 480 min in simulated physiological conditions. The experimental data were analyzed using different kinetic models in order to investigate the drug release mechanism. Among them, the semi-empirical Korsmeyer-Peppas and Peppas-Sahlin models were suitable to describe in vitro drug release mechanism of neomycin sulfate from the investigated hybrid hydrogels. The structural, viscoelastic, and swelling properties of PULL/PVA/protein hybrid hydrogels are influenced by their composition and preparation conditions, and they represent important factors for in vitro drug release behavior.

Green Light-Triggerable Chemo-Photothermal Activity of Cytarabine-Loaded Polymer Carbon Dots: Mechanism and Preliminary In Vitro Evaluation.

Carbon-based nanostructures are attracting a lot of attention because of their very low toxicity, excellent visible light-triggered optical and photothermal properties, and intriguing applications. Currently, the development of multifunctional carbon-based nanostructures for a synergistic chemo-photothermal approach is a challenging topic for the advancement of cancer treatment. Here, we report an unprecedented example of photoresponsive carbon-based polymer dots (CPDs-PNM) obtained by a one-pot thermal process from poly(N-isopropylacrylamide) (PNIPAM) without using organic solvent and additional reagents. The CPDs-PNM nanostructures were characterized by spectroscopic techniques, transmission electron microscopy, and atomic force microscopy. The CPDs-PNM exhibited high photothermal conversion efficiency, lower critical solution temperature (LCST) behavior, and good cytarabine (arabinosyl cytosine, AraC) loading capacity (62.3%). The formation of a CPDs-PNM/AraC adduct and photothermal-controlled drug release, triggered by green light excitation, were demonstrated by spectroscopic techniques, and the drug-polymer interaction and drug release mechanism were well supported by modeling simulation calculations. The cellular uptake of empty and AraC-loaded CPDs-PNM was imaged by confocal laser scanning microscopy. In vitro experiments evidenced that CPDs-PNM did not affect the viability of neuroblastoma cells, while the CPDs-PNM/AraC adduct under light irradiation exhibited significantly higher toxicity than AraC alone by a combined chemo-photothermal effect.

Application of zinc oxide nano-tube as drug-delivery vehicles of anticancer drug

Zinc oxide nano-tube (ZnONT) nano-structures, which possess chemical stability and non-toxicity in the human body, are considered promising for delivering different drugs. Within this work, we scrutinized the drug delivery capability of the ZnONT and its adsorptional properties as a drug delivery vehicle (DDV) for hydroxyurea (HU) as an anti-cancer drug through density functional theory along with the solvent impacts. Based on the optimized structures, it can be suggested that Zn atoms of ZnONT are the ideal sites on this nano-tube for the adsorption of HU. HU had a strong physical adsorption through the O atom of carbonyl groups onto the local pyramidal site of the ZnONT. At 1.96 Å and Ead of -39.28 kcal/mol, in the configuration which was favorable in terms of energy, there was an interaction between the O atoms of -C=O group of the drug and a Zn atom of the ZnONT. In order to scrutinize the excited state properties of the HU-ZnONT complex, we also examined the UV/Vis data of the HU/ZnONT interaction system. Following the adsorption of HU onto the surface of the ZnONT, there was a significant red-shift based on the maximum absorption wavelength, showing that the ZnONT is an ideal candidate for optic sensors in order to detect and monitor the drug molecule. HU could be released in the cancer tissues where pH was low based on the drug release mechanism. The current work thoroughly investigated the mechanism of interaction between the ZnONT and HU, showing that ZnONT can be used for the smart drug delivery of HU. Overall, the findings suggest that ZnONT could be used as an efficient drug-delivery system for the HU drug to treat various types of cancer. In this work we used B3LYP-gCP-D3 functional and the basis set LANL2DZ on the transition metal (Zn) and the basis set cc-pVDZ on the others. GAMESS software program was employed for performing the calculations. we performed analyses, including charge transport, molecular electrostatic potential surface (MEP), energetic, electronic, natural bond orbitals (NBOs), and structural optimizations.

Cell-mimicking polyethylene glycol-diacrylate based nanolipogel for encapsulation and delivery of hydrophilic biomolecule.

Lipid based nanoparticulate formulations have been widely used for the encapsulation and sustain release of hydrophilic drugs, but they still face challenges such as high initial burst release. Nanolipogel (NLG) emerges as a potential system to encapsulate and deliver hydrophilic drug while suppressing its initial burst release. However, there is a lack of characterization of the drug release mechanism from NLGs. In this work, we present a study on the release mechanism of hydrophilic Dextran-Fluorescein Isothiocyanate (DFITC) from Poly (ethylene glycol) Diacrylate (PEGDA) NLGs by using different molecular weights of PEGDA to vary the mesh size of the nanogel core, drawing inspiration from the macromolecular crowding effect in cells, which can be viewed as a mesh network of undefined sizes. The effect is then further characterized and validated by studying the diffusion of DFITC within the nanogel core using Fluorescence Recovery after Photobleaching (FRAP), on our newly developed cell derived microlipogels (MLG). This is in contrast to conventional FRAP works on cells or bulk hydrogels, which is limited in our application. Our work showed that the mesh size of the NLGs can be controlled by using different Mw of PEGDA, such as using a smaller MW to achieve higher crosslinking density, which will lead to having smaller mesh size for the crosslinked nanogel, and the release of hydrophilic DFITC can be sustained while suppressing the initial burst release, up to 10-fold more for crosslinked PEGDA 575 NLGs. This is further validated by FRAP which showed that the diffusion of DFITC is hindered by the decreasing mesh sizes in the NLGs, as a result of lower mobile fractions. These findings will be useful for guiding the design of PEGDA NLGs to have different degree of suppression of the initial burst release as well as the cumulative release, for a wide array of applications. This can also be extended to other different types of nanogel cores and other nanogel core-based nanoparticles for encapsulation and release of hydrophilic biomolecules.

Design of an Antibiotic-Releasing Polymer: Physicochemical Characterization and Drug Release Patterns.

Conventional drug delivery has its share of shortcomings, especially its rapid drug release with a relatively short duration of therapeutic drug concentrations, even in topical applications. Prolonged drug release can be effectively achieved by modifying the carrier in a drug delivery system. Among the several candidates for carriers studied over the years, poly (ether ether ketone), a biocompatible thermoplastic, was chosen as a suitable carrier. Its inherent hydrophobicity was overcome by controlled sulfonation, which introduced polar sulfonate groups onto the polymer backbone. Optimization of the sulfonation process was completed by the variation of the duration, temperature of the sulfonation, and concentration of sulfuric acid. The sulfonation was confirmed by EDS and the degree of sulfonation was determined by an NMR analysis (61.6% and 98.9%). Various physical properties such as morphology, mechanical strength, and thermal stability were studied using scanning electron microscopy, tensile testing, and thermogravimetric analysis. Cytotoxicity tests were performed on the SPEEK samples to study the variation in biocompatibility against a Vero cell line. The drug release kinetics of ciprofloxacin (CP) and nalidixic acid sodium salt (NA)-loaded membranes were studied in deionized water as well as SBF and compared against the absorbance of standardized solutions of the drug. The data were then used to determine the diffusion, distribution, and permeability coefficients. Various mathematical models were used to fit the obtained data to establish the order and mechanism of drug release. Studies revealed that drug release occurs by diffusion and follows zero-order kinetics.

Studying Ga and Ge-doped AlP nanotube as a drug carrier for ciclopirox anticancer drug using DFT

The impact of Ga and Ge-doping on the ciclopirox (CPX) drug delivery performance of an AlP nanotube (AlPNT) was scrutinized computationally. It was found that the pristine AlPNT was not a good choice for this drug delivery. Doping of the Ga and Ge into the AlPNT increased the adsorption energy of CPX from −8.0 to −26.8 and −29.2 kcal/mol, respectively. The Ge atom considerably contributed to the generation of the virtual orbitals of the Ge-doped AlPNT, which showed that this atom was suitable for nucleophilic attack compared to the Al atoms. Finally, the adsorption performance and capacity of CPX increased after doping Ga and Ge, which made the AlPNT more suitable for drug delivery. A mechanism for drug release was introduced in cancerous tissues, which showed that in cancerous cells with low pH, CPX was significantly protonated, which led to the separation of CPX from the Ge-doped AlPNT.

BOX-BEHNKEN DESIGN FOR OPTIMIZATION OF FORMULATION VARIABLES FOR CONTROLLED RELEASE GASTRORETENTIVE TABLET OF VERAPAMIL HYDROCHLORIDE

Objective: To develop a Verapamil hydrochloride controlled release gastro-retentive (CRGR) tablet for once-daily dosing using the response surface Box-Behnken Design (BBD) approach for the improvement of bioavailability and reduction in dosing frequency to overcome the issues related to the conventional tablet formulation. Methods: For the optimization, 33Box-Behnken design was used. The independent variables were selected, the amount of Compritol 888 ATO (A), HPMC K15M (B), and Sodium bicarbonate (C). The dependent variables were Cumulative % drug release in 1.5 h (Q1.5), 8 h (Q8), 24 H (Q24) and floating lag time (FLT). Flow properties of pre-compressed powder, physical characteristics, drug content, floating lag time, total floating time and in vitro dissolution study of all formulation were assessed. In vitro dissolution study of optimized formulation that was prepared experimentally was performed and compared with predicted data obtained from the software. Drug release kinetics of the optimized formulation was also assessed to know the mechanism of drug release from the CRGR tablets. Results: Responses of experimental runs were found as Q1.5: 12.78-33.62 (%), Q8: 43.03-64 (%), Q24: 78.77 to 103.57 (%) and floating lag time as 3.01 min to 5.08 min. The predicted optimized formula with the highest desirability value of 0.963 containing amount 126.030 mg, 160.00 mg and 80.955 mg of Compritol 888 ATO, HPMC K15M and Sodium biarbonate respectively was prepared and evaluated. The experimental values from optimized formulation were obtained as Q1.5: 23.397%, Q8; 57.744%, Q24: 97.150% and FLT: 3.12 min. Predicted and experimental results were found comparable for all the responses. The release data from the optimized formulation were best fitted in the Higuchi (r2 = 0.999) and the Korsmeyer-Peppas ((r2 = 0.998, n=0.54) model. The in vitro drug release studies indicated that the Verapamil hydrochloride gastroretentive tablet releases the drug in controlled manner for 24 h. Conclusion: This study found that using Box-Behnken Design with the response and variable relation, it is possible to achieve an optimum formulation with desirable characteristics. This study also established the suitability of Compritol 888 ATO-HPMC K15M combination with Sodium bicarbonate to increase the gastric residence time tablet formulation had once-daily dosing of the Verapamil Hcl with improved bioavailability for effective management of hypertension.

Physicochemical properties, pharmacokinetics, toxicology and application of nanocarriers.

As a promising delivery nanosystem for drug controlled-release, nanocarriers (NCs) have been investigated widely. Although various studies have concentrated on the preparation and characterization of nanoparticles (NPs), clinical applications are rarely reported, due to the unclear distribution, absorption, metabolism, toxicology processes and drug release mechanism. The clinical application of NCs is therefore still a long way off. This review describes the effects of the properties of NCs (including size, shape, surface properties, porosity, elasticity and so on) on pharmacological and toxicological behaviours in vivo and medical applications. Moreover, this study is intended to help the readers understand the behaviours and mechanisms of NCs and positively face the challenges caused by the variety of complicated and limited processes of NCs in vivo. Importantly, this article provides some strategies for the clinical application of NCs and may provide ideas to enhance the therapeutic efficacy of NCs without increasing the toxicology, by introducing tracing technology, which can be more suitable in contributing to the development of safety and efficacy of NCs and the growth of nanotechnology.

The iron group transition-metal (Fe, Ru, Os) coordination of Se-doped graphitic carbon (Se@g-C3N4) nanostructures for the smart therapeutic delivery of zidovudine (ZVD) as an antiretroviral drug: a theoretical calculation perspective.

This study employed density functional theory (DFT) computational techniques at the ωB97XD/def2svp level of theory to comprehensively explore the electronic behavior of Fe-group transition metal (Fe, Ru, Os) coordination of Se-doped graphitic carbon (Se@g-C3N4) nanosystems in the smart delivery of zidovudine (ZVD), an antiretroviral drug. The HOMO-LUMO results of the interactions show a general reduction in energy gap values across all complexes in the following order: ZVD_Se@C3N4 < ZVD_Ru_Se@C3N4 < ZVD_Fe_Se@C3N4 < ZVD_Os_Se@C3N4. ZVD_Se@C3N4 exhibits the smallest post-interaction band gap of 3.783 eV, while ZVD_Os_Se@C3N4 presents the highest energy band gap of 5.438 eV. Results from the corrected adsorption energy (BSSE) revealed that Os_Se@C3N4 and Ru_Se@C3N4 demonstrated more negative adsorption energies of -2.67 and -2.701 eV, respectively, pointing to a more favorable interaction between ZVD and these systems, thus potentially enhancing the drug delivery efficiency. The investigation into the drug release mechanism from the adsorbents involved a comprehensive examination of the dipole moment and the influence of pH, shedding light on the controlled release of ZVD. Additionally, investigating the energy decomposition analysis (EDA) revealed that ZVD_Ru_Se@C3N4 and ZVD_Fe_Se@C3N4 exhibited the same total energy of -787.7 kJ mol-1. This intriguing similarity in their total energy levels suggested that their stability was governed by factors beyond reactivity, possibly due to intricate orbital interactions. Furthermore, analyzing the bond dissociation energies showed that all systems exhibited negative enthalpy values, indicating that these systems were exothermic at both surface and interaction levels, thus suggesting that these processes emitted heat, contributing to the surrounding thermal energy.

Metadynamics simulations for the investigation of drug loading on functionalized inorganic nanoparticles.

Inorganic nanoparticles show promising properties that allow them to be efficiently used as drug carriers. The main limitation in this type of application is currently the drug loading capacity, which can be overcome with a proper functionalization of the nanoparticle surface. In this study, we present, for the first time, a computational approach based on metadynamics to estimate the binding free energy of the doxorubicin drug (DOX) to a functionalized TiO2 nanoparticle under different pH conditions. On a thermodynamic basis, we demonstrate the robustness of our approach to capture the overall mechanism behind the pH-triggered release of DOX due to environmental pH changes. Notably, binding free energy estimations align well with what is expected for a pH-sensitive drug delivery system. Based on our results, we envision the use of metadynamics as a promising computational tool for the rational design and in silico optimization of organic ligands with improved drug carrier properties.

Biodegradable Gg-cl-poly(NIPAm-co-AA)/-o-MWCNT based hydrogel for combined drug delivery system of metformin and sodium diclofenac: in vitro studies.

In the present study Gg-cl-poly(NIPA-co-AA) and Gg-cl-poly(NIPA-co-AA)/-o-MWCNT hydrogels were synthesized using free radical polymerization. We looked into whether combining metformin with diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), would be effective in examining complex formation and analysing the types and intensities of complexes that could result from metformin-diclofenac interactions. The interaction of metformin and diclofenac was studied in vitro at various pH levels and body temperatures. The structure and morphology of the produced hydrogel were characterised using FTIR spectra, SEM analysis, and drug loading tests. As a model drug, the hydrogel was loaded with metformin hydrochloride and sodium diclofenac (DS), and the medicines were released pH-dependently. To explore the drug release kinetics and mechanism, the zero order and first order kinetic models, the Korsemeyar-Peppas model, the Higuchi model, and the Hixson-Crowell model have all been employed. Drug release studies revealed notable characteristics in connection to physiologically predicted pH values, with a high release rate at pH = 9.2. At pH = 9.2, however, both metformin and sodium diclofenac exhibited a Fickian mechanism. Combination treatment may reduce the effective dose of a single drug and hinder metabolic rescue mechanisms. More study is needed to detect any negative effects on individuals.

Exploring release mechanisms by disrupting π-π stacking regions in stable micelles.

π-π stacking strategies can enhance the stability performance of delivery platforms but are often restricted by incomplete drug release performance, even with the help of crosslinking strategies. Therefore, there has been considerable interest in enhancing the drug release performance by disrupting the π-π stacking region (structural rearrangements). Herein, we synthesized poly(3-(isobutyloxy)-2-oxopropyl benzoate)-b-poly(2-hydroxybutyl methacrylate)-co-poly((ethylene glycol)methylether methacrylate) [PBOOPMA-b-P(HBMA-co-PEGMA), PHB] and revealed the drug release mechanism of PHB-based micelles. The structural rearrangements derived from the crosslinking strategy were revealed to improve the early release performance by 43-55% using micellar dissolutions. Moreover, the esterase-responsive strategy was elucidated to induce reassembly with 77-79% size variation, intensifying the structural rearrangements, which was also synergistic with the crosslinking strategy. Based on the advantages of improving drug release performance, the esterase-responsive strategy was considered a promising candidate for enhancing late release performance. Meanwhile, it is believed that such responsive modulation (crosslinking, esterase-responsive) in the π-π stacking region will become highly promising for subsequent research. Finally, the biosafety of 95.81% at 400 mg L-1 and drug cytotoxicity of IC50 ≈ 2.5 mg L-1 of PHB-EDE@CPT were also validated, confirming the broad application prospects of PHB-based crosslinked micelles.

Gold embedded gum ghatti grafted polyacrylamide nanocomposite for in vitro release study of curcumin

Nanoparticle systems are highly fascinating because of their unique physicochemical properties. Gold nanoparticles (Au NPs) can be applied in medical applications due to its biocompatibility and chemical nontoxicity. In this work, gold-embedded gum ghatti-grafted polyacrylamide (Gg-g-AM(Au)) nanocomposite was synthesized via an in situ polymerization method. The synthesized Gg-g-AM(Au) nanocomposite was characterized by using various techniques such as UV–visible spectroscopy, FTIR, XRD and FESEM. The Gg-g-AM(Au) nanocomposite was used for in vitro release of curcumin at pH 1.2 and 7.4. To evaluate drug release mechanisms and kinetics, the release data were fitted to zero order, first order, Korsmeyer-Peppas, and Higuchi models. The antibacterial behavior of the nanocomposite systems was also investigated. The Gg-g-AM(Au) nanocomposite systems can be considered as a good carrier towards in vitro release of the curcumin.

Inhalable Formulations to Treat Non-Small Cell Lung Cancer (NSCLC): Recent Therapies and Developments.

Cancer has been the leading cause of mortalities, with lung cancer contributing 18% to overall deaths. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. The primary form of therapy used to treat lung cancer still includes oral and systemic administration of drugs, radiotherapy, or chemotherapy. Some patients have to go through a regime of combination therapy. Despite being the only available form of therapy, their use is limited due to the adverse effects, toxicity, and development of resistance over prolonged use. This led to a shift and progressive evolution into using pulmonary drug delivery systems. Being a non-invasive method of drug-administration and allowing localized delivery of drugs to cancer cells, inhalable drug delivery systems can lead to lower dosing and fewer systemic toxicities over other conventional routes. In this way, we can increase the actual local concentration of the drug in lungs, which will ultimately lead to better antitumor therapy. Nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening, and tracking. Regardless of the advantages, pulmonary delivery is still in the early stages of development and various factors such as pharmacology, immunology, and toxicology should be taken into consideration for the development of suitable inhalable nano-based chemotherapeutic drugs. They face numerous physiological barriers such as lung retention and efficacy, and could also lead to toxicity due to prolonged exposure. Nano-carriers with a sustained drug release mechanism could help in overcoming these challenges. This review article will focus on the various inhalable formulations for targeted drug delivery, including nano-based delivery systems such as lipids, liposome, polymeric and inorganic nanocarriers, micelles, microparticles and nanoaggregates for lung cancer treatment. Various devices used in pulmonary drug delivery loaded on various nano-carriers are also discussed in detail.