Site-specific Drug Release Research Articles

In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review.

Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases.

Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders.

Treatment of diseases of oxidative stress through activation of the antioxidant nuclear factor E2-related factor 2 (NRF2) is limited by systemic side effects. We chemically functionalize the NRF2 activator monomethyl fumarate to require Baeyer-Villiger oxidation for release of the active drug at sites of oxidative stress. This prodrug reverses chronic pain in mice with reduced side effects and could be applied to other disorders of oxidative stress.

Next-generation pediatric care: nanotechnology-based and AI-driven solutions for cardiovascular, respiratory, and gastrointestinal disorders.

Global pediatric healthcare reveals significant morbidity and mortality rates linked to respiratory, cardiac, and gastrointestinal disorders in children and newborns, mostly due to the complexity of therapeutic management in pediatrics and neonatology, owing to the lack of suitable dosage forms for these patients, often rendering them "therapeutic orphans". The development and application of pediatric drug formulations encounter numerous challenges, including physiological heterogeneity within age groups, limited profitability for the pharmaceutical industry, and ethical and clinical constraints. Many drugs are used unlicensed or off-label, posing a high risk of toxicity and reduced efficacy. Despite these circumstances, some regulatory changes are being performed, thus thrusting research innovation in this field. Up-to-date peer-reviewed journal articles, books, government and institutional reports, data repositories and databases were used as main data sources. Among the main strategies proposed to address the current pediatric care situation, nanotechnology is specially promising for pediatric respiratory diseases since they offer a non-invasive, versatile, tunable, site-specific drug release. Tissue engineering is in the spotlight as strategy to address pediatric cardiac diseases, together with theragnostic systems. The integration of nanotechnology and theragnostic stands poised to refine and propel nanomedicine approaches, ushering in an era of innovative and personalized drug delivery for pediatric patients. Finally, the intersection of drug repurposing and artificial intelligence tools in pediatric healthcare holds great potential. This promises not only to enhance efficiency in drug development in general, but also in the pediatric field, hopefully boosting clinical trials for this population. Despite the long road ahead, the deepening of nanotechnology, the evolution of tissue engineering, and the combination of traditional techniques with artificial intelligence are the most recently reported strategies in the specific field of pediatric therapeutics.

Light-Responsive conjugated polymer nanoparticles with Spatial-Controlled camptothecin release via π − π stacking for improved Combinatorial therapy of breast cancer

The treatment of breast cancer (BC) remains a significant challenge, exemplified by the limitations of chemotherapy due to its high side effects. Light-responsive drug delivery systems (DDS) offer a promising approach to spatially and temporally release drugs, minimizing chemotherapy side effects and enhancing efficacy. However, achieving precise delivery and site-specific drug release poses complex challenges. Here, We present a novel nano-system combining light-responsive photothermal therapy (PTT) with photothermal-responsive chemotherapy via π − π Stacking. Conjugated polymer nanoparticles (cRGD-PTer N25/CPT NPs) is designed for spatiotemporal targeted PTT/chemotherapy. Research shows that the strong near-infrared absorption of PTer N25 endows cRGD-PTer N25/CPT NPs with excellent photothermal capabilities(57.4 %) and near-infrared laser-triggered drug release performance. The cRGD-PTer N25/CPT NPs enhanced BC-specific cellular accumulation, prolonged blood circulation, exhibited good biocompatibility, and improved PTT and chemotherapy efficacy in BC cell lines and mouse models while reducing systemic toxicity. The photothermal effect triggered the on-demand release of camptothecin (CPT), producing therapeutic effects and downregulating heat shock protein 70 (HSP 70), reducing cancer cell thermoresistance, and enhancing combined treatment efficacy. Under spatial and temporal control, the tumor growth inhibition rate of the cRGD-PTer N25/CPT NPs group reached 93.6 %, nearly eradicating tumor presence, whereas the control group exhibited only partial inhibition. Minimal cardiotoxicity and metastatic side effects are not observed. This work presents a viable strategy for designing novel controlled-release drug systems to improve breast cancer treatment efficiency.

Development of Drug-Loaded PCL@MOF Film Enclosed in a Photo Polymeric Container for Sustained Release.

The programmed fabrication of oral dosage forms is associated with several challenges such as controlled loading and disintegration. To optimize the drug payload, excipient breakdown, and site-specific sustained release of hydrophobic drug (sulfamethoxazole, SM), we propose the development of acrylate polymer tablets enclosed with drug-loaded polycaprolactone (PCL) films. The active pharmaceutical ingredient (API) is physisorbed into the porous iron (Fe)-based metal-organic framework (MOF) and later converted to tangible PCL films, which, upon folding, are incorporated into the acrylate polymer matrices (P1/P2/P3). X-ray powder diffraction (XRPD) analysis and scanning electron microscopy (SEM) micrographs confirmed the stability and homogeneous distribution of MOF within the 50 μm thick film. Adsorption-desorption measurements at ambient temperatures confirmed the decrease in the BET surface area of PCL films by 40%, which was ∼3.01 m/g, and pore volume from 30 to 9 nm. The decrease in adsorption and surface parameters could confirm the gradual accessibility of SM molecules once exposed to a degrading environment. Fourier transform infrared (FTIR) analyses of in vitro dissolution confirmed the presence of the drug in the MOF-PCL film-enclosed tablets and concluded the cumulative SM release at pH ∼ 8.2 which followed the order SM@Fe-MOF < P1/P2/P3 < PCL-SM@Fe-MOF < P1/PCL-SM@Fe-MOF < P3/PCL-SM@Fe-MOF. The results of the study indicate that the P3/PCL-SM@Fe-MOF assembly has potential use as a biomedical drug delivery alternative carrier for effective drug loading and stimuli-responsive flexible release to attain high bioavailability.

The Advancing Role of Nanocomposites in Cancer Diagnosis and Treatment.

The relentless pursuit of effective cancer diagnosis and treatment strategies has led to the rapidly expanding field of nanotechnology, with a specific focus on nanocomposites. Nanocomposites, a combination of nanomaterials with diverse properties, have emerged as versatile tools in oncology, offering multifunctional platforms for targeted delivery, imaging, and therapeutic interventions. Nanocomposites exhibit great potential for early detection and accurate imaging in cancer diagnosis. Integrating various imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging, into nanocomposites enables the development of contrast agents with enhanced sensitivity and specificity. Moreover, functionalizing nanocomposites with targeting ligands ensures selective accumulation in tumor tissues, facilitating precise imaging and diagnostic accuracy. On the therapeutic front, nanocomposites have revolutionized cancer treatment by overcoming traditional challenges associated with drug delivery. The controlled release of therapeutic agents from nanocomposite carriers enhances drug bioavailability, reduces systemic toxicity, and improves overall treatment efficacy. Additionally, the integration of stimuli-responsive components within nanocomposites enables site-specific drug release triggered by the unique microenvironment of the tumor. Despite the remarkable progress in the field, challenges such as biocompatibility, scalability, and long-term safety profiles remain. This article provides a comprehensive overview of recent developments, challenges, and prospects, emphasizing the transformative potential of nanocomposites in revolutionizing the landscape of cancer diagnostics and therapeutics. In Conclusion, integrating nanocomposites in cancer diagnosis and treatment heralds a new era for precision medicine.

Design and Evaluation of Gastro-Retentive Floating Tablets of Ibandronic acid

The objective of this study is Preparation and evaluation of gastro-retentive floating tablets of Ibandronic acid by direct compression method polymers or combination. In this study, Ibandronic acid, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastro retentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDDs are an approach to prolong gastric residence time, there by targeting site-specific drug release in the upper GIT for local or systemic effect. GRDF tablets of Ibandronic acid (200 mg) were characterized with the effects of Carbopol 934P, HPMC 4KM and Na-CMC at various ratios on swelling, floating, physical integrity. A prolonged dissolution profile of Ibandronic acid GRDF tablets developed in this study was observed for its thickness, friability, hardness, drug content and in-vitro drug release. Formulated Floating tablets of Ibandronic acid gave satisfactory results for various physicochemical parameters like hardness, friability, thickness, weight variation and content uniformity. Sodium bicarbonate has predominant effect on the buoyancy lag time, while HPMC K4M has predominant effect on total floating time and drug release. From the study it is evident that a promising controlled release floating tablets of Ibandronic acid can be developed to increase gastric residence time and thereby increasing its bioavailability. Both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug. Keywords: Gastro retention, Ibandronic acid, floating tablet, Carbopol, GRDF, GRFT.

Nanotechnology Integrated Innovative Drug Delivery and Therapy for Cancer.

Cancer remains a significant global health challenge, necessitating innovative approaches to enhance the efficacy and specificity of therapeutic interventions while minimizing adverse effects on healthy tissues. Nanotechnology has emerged as a promising avenue in cancer treatment, offering novel strategies for targeted drug delivery. Nanoparticles, liposomes, and polymer-based systems have played pivotal roles in revolutionizing cancer therapy. Nanotechnology possesses unique physicochemical properties, enabling efficient encapsulation of therapeutic agents and controlled and prolonged release at tumour sites. Advancement in formulations using nanotechnology has made it possible to make multifunctional systems that respond to the microenvironment of a tumour by releasing payloads in response to changes in pH, temperature, or enzymes. Stimuli-responsive polymers can release drugs in response to external cues, enabling site-specific drug release and minimizing systemic exposure. This review explores recent studies and preclinical trials that show how nanoparticles, liposomes, and polymerbased systems could be used to treat cancer, discussing challenges such as scalability, regulatory approval, and potential toxicity concerns along with patents published recently.

Controlled Dissociation of Polymeric Micelles in Response to Oxidative Stress.

Nanoparticle-based drug carriers that can respond to oxidative stress in tumor tissue have attracted attention for site-specific drug release. Taking advantage of the characteristic microenvironment in tumors, one of the attractive directions in drug delivery research is to design drug carriers that release drugs upon oxidation. A strategy to incorporate oxidation-sensitive thioether motifs such as thiomorpholine acrylamide (TMAM) to drug carriers has been often used to achieve oxidation-induced dissociation, thereby targeted drug release. However, those delivery systems often suffer from a slow dissociation rate due to the intrinsic hydrophobicity of the thioether structures. In this study, we aimed to enhance the dissociation rate of TMAM-based micelles upon oxidation. The random copolymers of N-isopropylacrylamide and TMAM (P(NIPAM/TMAM)) were designed as an oxidation-sensitive segment that showed a fast response to oxidative stress. We first synthesized P(NIPAM/TMAM) copolymers with different NIPAM:TMAM molar ratios. Those copolymers exhibited low critical solution temperatures (LCSTs) below 32 °C, which shifted to higher temperatures after oxidation. The changes in LCSTs depend on the NIPAM:TMAM molar ratios. At the NIPAM:TMAM molar ratio of 82:18, the LCSTs before and after oxidation were 17 and 54 °C, respectively. We then prepared micelles from the diblock copolymers of poly(N-acryloyl morpholine) (PAM) and P(NIPAM/TMAM). The micelles showed an accelerated dissociation rate upon oxidation compared to the micelles without NIPAM units. Furthermore, the doxorubicin (Dox)-loaded micelles showed enhanced relative toxicity in human colorectal cancer (HT29) cells over human umbilical vein endothelial cells (HUVECs). Our novel strategy to design an oxidation-sensitive micellar core comprising a P(NIPAM/TMAM) segment can be used as a chemotherapeutic delivery system that responds to an oxidative tumor microenvironment in an appropriate time scale.

Recent Advances in pH and Redox Responsive Polymer Nanocomposites for Cancer Therapy

Cancer therapy currently focuses on personalized targeted treatments. A promising approach uses stimuli-responsive biomaterials for site-specific drug release, such as pH- and redox-triggered polymer nanocomposites. These materials respond to the tumor microenvironment, enhance efficacy, and reduce off-target effects. Cancer cells with anomalous properties such as acidic cytosolic pH and elevated redox potential are targeted by these biomaterials. An imbalance in ions and biological thiols in the cytoplasm contributes to tumor growth. Functionalized polymer nanocomposites with large surface areas and specific targeting outperform conventional small-molecule materials. To overcome problems such as low bioavailability, uncontrolled drug release, and poor cell penetration, multifunctional nanomaterials make it easier for drugs to enter certain cellular or subcellular systems. High therapeutic efficacy is achieved through surface functionalization, site-specific targeting, and the use of stimuli-responsive components. In particular, pH and redox dual-stimuli-based polymeric nanocomposites for cancer therapeutics have scarcely been reported. This article provides recent progress in pH- and redox-responsive polymer nanocomposites for site-specific drug delivery in cancer therapy. It explores the design principles, fabrication methods, mechanisms of action, and prospects of these dual-stimuli-responsive biomaterials.

N-Sulfonyl amidine polypeptides: new polymeric biomaterials with conformation transition responsive to tumor acidity.

Manipulation of pH responsiveness is a frequently employed tactic in the formulation of trigger-responsive nanomaterials. It offers an avenue for "smart" designs capitalizing on distinctive pH gradients across diverse tissues and intracellular compartments. However, an overwhelming majority of documented functional groups (>80%) exhibit responsiveness solely to the heightened acidic milieu of intracellular pH (about 4.5-5.5). This scenario diverges markedly from the moderately acidic extracellular pH (∼6.8) characteristic of tumor microenvironments. Consequently, systems predicated upon intracellular pH responsiveness are unlikely to confer discernible advantages concerning targeted penetration and cellular uptake at tumor sites. In this study, we elucidated the extracellular pH responsiveness intrinsic to N-sulfonyl amidine (SAi), delineating a method to synthesize an array of SAi-bearing polypeptides (SAi-polypeptides). Notably, we demonstrated the pH-dependent modulation of SAi-polypeptide conformations, made possible by the protonation/deprotonation equilibrium of SAi in response to minute fluctuations in pH from physiological conditions to the extracellular milieu of tumors. This dynamic pH-triggered transition of SAi-polypeptides from negatively charged to neutrally charged side chains at the pH outside tumor cells (∼6.8) facilitated a transition from coil to helix conformations, concomitant with the induction of cellular internalization upon arrival at tumor sites. Furthermore, the progressive acidification of the intracellular environment expedited drug release, culminating in significantly enhanced site-specific chemotherapeutic efficacy compared with free-drug counterparts. The distinct pH-responsive attributes of SAi could aid the design of tumor acidity-responsive applications, thereby furnishing invaluable insights into the realm of smart material design.

PH/redox responsive size‐switchable intelligent nanovehicle for tumor microenvironment targeted DOX release

Tumor microenvironment (TME) targeted strategy could control the drug release in tumor cells more accurately and creates a new opportunity for enhanced site-specific targeted delivery. In this study, (PAA-b-PCL-S-S-PCL-b-PAA) copolymeric nanoparticles (NPs) with size-switchable ability and dual pH/redox-triggered drug release behavior were designed to significantly promote cancer uptake (cell internalization of around 100% at 30 min) and site-specific targeted doxorubicin (DOX) delivery in MDA-MB-231 tumor cells. NPs surface charge was shifted from − 17.8 to − 2.4 and their size shrunk from 170.3 to 93 nm in TME. The cell cycle results showed that DOX-loaded NPs showed G2/M (68%) arrest, while free DOX showed sub-G1 arrest (22%). Apoptosis tests confirmed that the cells treated with DOX-loaded NPs showed a higher amount of apoptosis (71.6%) than the free DOX (49.8%). Western blot and RT-PCR assays revealed that the apoptotic genes and protein levels were significantly upregulated using the DOX-loaded NPs vs. the free DOX (Pvalue < 0.001). In conclusion, dual pH/redox-responsive and size-switchable DOX-loaded NPs developed here showed outstanding anti-tumoral features compared with free DOX that might present a prospective platform for tumor site-specific accumulation and drug release that suggest further in vivo research.

Nanomaterial marvels: Pioneering applications and cutting-edge advancements in drug delivery

Nanotechnology has revolutionized the field of medicine, particularly in the development of novel drug delivery systems. Nanomaterial-based drug delivery systems offer several advantages over traditional methods, including enhanced therapeutic efficacy, improved bioavailability, targeted delivery, and reduced side effects. This review provides an overview of the applications and recent advancements in nanomaterial-based drug delivery systems. The first section of this review focuses on the different types of nanomaterials used in drug delivery, including liposomes, polymeric nanoparticles, dendrimers, carbon-based nanomaterials, and metallic nanoparticles. Each nanomaterial has unique physicochemical properties that can be tailored to optimize drug encapsulation, release, and targeting. The second section highlights the importance of nanoscale characterization techniques in evaluating the properties and performance of nanomaterial-based drug delivery systems. Characterization techniques such as dynamic light scattering, transmission electron microscopy, atomic force microscopy, and spectroscopic methods enable researchers to analyze particle size, morphology, surface charge, drug loading, and release kinetics. The third section discusses the application of nanomaterial-based drug delivery systems in various therapeutic areas, including cancer treatment, cardiovascular diseases, infectious diseases, and neurological disorders. These systems can be engineered to selectively accumulate at the target site, enhancing drug efficacy and minimizing off-target effects. The fourth section explores recent advancements in nanomaterial-based drug delivery systems, including stimulus-responsive and multifunctional nanocarriers. Stimuli-responsive systems can release drugs in response to specific triggers, such as changes in pH, temperature, or enzymatic activity, leading to site-specific drug release. Multifunctional nanocarriers combine drug delivery with diagnostic imaging, allowing real-time monitoring of drug distribution and therapeutic response. The final section addresses the challenges and future perspectives in the field of nanomaterial-based drug delivery systems. Challenges include regulatory considerations, toxicity concerns, scalability, and clinical translation. Future directions involve the development of personalized nanomedicine, combination therapy approaches, and integration with other emerging technologies, such as artificial intelligence and gene editing. In conclusion, nanomaterial-based drug delivery systems have shown great potential for improving the efficacy and safety of therapeutic interventions. The advancements in nanotechnology offer exciting opportunities for the development of next-generation drug delivery platforms, opening new avenues for personalized medicine and targeted therapies. However, further research and collaborations are required to address the challenges associated with clinical translation and ensure the safe and effective implementation of these systems in clinical practice.

Development of Robust Cationic Light-Activated Thermosensitive Liposomes: Choosing the Right Lipids.

Extensive research has been conducted on cationic light-activated thermosensitive liposomes (CLTSLs) as a means for site-specific and controlled drug release; however, less attention has been given to the stability of these nanoparticles. Selecting the appropriate lipids is crucial for the development of a stable and responsive system. In this study, we investigated the impact of various lipids on the physical properties of cationic light-activated liposomes. Incorporating poly(ethylene glycol) PEG molecules resulted in uniform liposomes with low polydispersity index, while the addition of unsaturated lipid (DOTAP) resulted in extremely leaky liposomes, with almost 80% release in just 10 min of incubation at body temperature. Conversely, the inclusion of cholesterol in the formulation increased liposome stability too much and decreased their sensitivity to stimuli-responsive release, with only 14% release after 2 min of light exposure. To achieve stable and functional CLTSL, we substituted an equivalent amount of unsaturated lipid with a saturated lipid (DPTAP), resulting in stable liposomes at body temperature that were highly responsive to light, releasing 90% of their content in 10 s of light exposure. We also conducted two atomistic molecular dynamics simulations using lipid compositions with saturated and unsaturated lipids to investigate the effect of lipid composition on the dynamical properties of the liposomal lipid bilayer. Our findings suggest that the nature of lipids used to prepare liposomes significantly affects their properties, especially when the drug loading needs to be stable but triggered drug release properties are required at the same time. Selecting the appropriate lipids in the right amount is therefore essential for the preparation of liposomes with desirable properties.

Phenylboronic acid conjugated PAMAM G4 dendrimers augmented usnic acid delivery to gastric cancer cells

Here we report on the synthesis, characterization, and biological evaluation of Siglec’s targeted G4 PAMAM dendrimers loaded with usnic acid (UA). Siglec's targeted G4 dendrimers were obtained by conjugation of 4-carboxy phenylboronic acid (PBA) to the periphery of the G4 PAMAM dendrimer (PBA-PAMAM). UA-loaded PBA-PAMAM dendrimers (UA@PBA-PAMAM) showed average particle size (18 nm) without any sign of aggregation with amorphous nature, stability of the drug, and PBA-mediated anticancer efficacy. The UA@PBA-PAMAM dendrimer formulation showed a site-specific drug release profile. After 12 h, 17.6% and 95.7% of UA was released from UA@PBA-PAMAM dendrimer formulation in pH 7.4 and pH 5.0, respectively. In vitro anticancer results suggested the no cytotoxicity of G4 dendrimers after PBA conjugation. The cell viability of AGS cells was observed as 88.9 ± 0.7% (12 h) and 50.4 ± 1.9% (24 h) after pure UA treatment and 37.3 ± 0.6% (12 h) and 14.4% ± 1.2 (24 h) after treatment with UA@PBA-PAMAM. The pure UA had IC50 values of 44.9 ± 3.1 μg/mL (for 12 h) and 8.2 ± 1.1 μg/mL (for 24 h) while UA@PBA-PAMAM had an IC50 value of 8.4 ± 0.3 μg/mL (for 12 h) and 2.7 ± 0.4 μg/mL (for 24 h) in AGS cells. As a result of cytotoxicity studies, the dendrimer formulation UA@PBA-PAMAM maintained its effectiveness and was able to produce a long-term anticancer effect over time compared to the pure UA dose. The PBA-PAMAM dendrimer also significantly enhanced the cellular internalization in AGS gastric cancer cells. The new PBA-PAMAM design appears to be suitable nanocarriers for the UA to deliver gastric cancer cells.

Cooling-induced, localized release of cytotoxic peptides from engineered polymer nanoparticles in living mice for cancer therapy.

Temperature-responsive polymers are often characterized by an abrupt change in the degree of swelling brought about by small changes in temperature. Polymers with a lower critical solution temperature (LCST) in particular, are important as drug and gene delivery vehicles. Drug molecules are taken up by the polymer in their solvent swollen state below their LCST. Increasing the temperature above the LCST, typically physiological temperatures, results in desolvation of polymer chains and microstructure collapse. The trapped drug is released slowly by passive diffusion through the collapsed polymer network. Since diffusion is dependent on many variables, localizing and control of the drug delivery rate can be challenging. Here, we report a fundamentally different approach for the rapid (seconds) tumor-specific delivery of a biomacromolecular drug. A copolymer nanoparticle (NP) was engineered with affinity for melittin, a peptide with potent anti-cancer activity, at physiological temperature. Intravenous injection of the NP-melittin complex results in its accumulation in organs and at the tumor. We demonstrate that by local cooling of the tumor the melittin is rapidly released from the NP-melittin complex. The release occurs only at the cooled tumor site. Importantly, tumor growth was significantly suppressed using this technique demonstrating therapeutically useful quantities of the drug can be delivered. This work reports the first example of an in vivo site-specific release of a macromolecular drug by local cooling for cancer therapy. In view of the increasing number of cryotherapeutic devices for in vivo applications, this work has the potential to stimulate cryotherapy for in vivo drug delivery.

Direct cyclodextrin based powder extrusion 3D printing of budesonide loaded mini-tablets for the treatment of eosinophilic colitis in paediatric patients

The purpose of this study was to combine direct powder extrusion (DPE) 3D printing and fluid bed coating techniques to create a budesonide (BD) loaded solid oral formulations for the treatment of eosinophilic colitis (EC) in paediatric patients. The preferred medication for EC treatment is BD, which has drawbacks due to its poor water solubility and low absorption. Additionally, since commercially available medications for EC treatment are created and approved for adult patients, administering them to children sometimes requires an off-label use and an impromptu handling, which can result in therapeutic ineffectiveness. The DPE 3D approach was investigated to create Mini-Tablets (MTs) to suit the swallowing, palatability, and dose flexibility control requirements needed by paediatric patients. Additionally, DPE 3D and the inclusion of hydroxypropyl-β-cyclodextrin in the initial powder mixture allowed for an improvement in the solubility and rate of BD dissolution in aqueous medium. Then, to accomplish a site-specific drug release at the intestinal level, MTs were coated with a layer of Eudragit FS 30D, an enteric polymer responsive at pH > 7.0 values. In vitro release experiments showed that film-coated MTs were suitable in terms of size and dose, enabling potential therapeutic customization and targeted delivery of BD to the colon.

Size-switchable polymer-based nanomedicines in the advanced therapy of rheumatoid arthritis.

Chronic inflammatory diseases such as rheumatoid arthritis represent a substantial socio-economic impact and have a high prevalence in the modern world. Nano-sized polymer therapeutics have shown suitable characteristics for becoming the next generation of anti-inflammatory nanomedicines. Here, we present biocompatible and stimuli-sensitive N-(2-hydroxypropyl)methacrylamide based polymer conjugates with the anti-inflammatory drug dexamethasone (DEX), which has been tailored for prolonged blood circulation, enhanced inflammatory site accumulation, site-specific drug release and subsequent elimination of the carrier via urine excretion. The hydrodynamic size of novel polymer-DEX nanomedicine was adjusted to prolong its blood circulation whilst maintaining the renal excretability of the polymer carrier after drug release in inflamed tissue. The therapeutic efficacy of the studied polymer nanomedicines was evaluated in a model of dissipated chronic arthritis, i.e. collagen II-induced arthritis, in mice. The pH-sensitive drug attachment enabled enhanced blood circulation with minimal systemic drug release, as well as rapid drug activation in affected joints. Importantly, unlike free DEX, the polymer nanomedicines were able to diminish joint inflammation and arthritis-induced bone damage - even at a reduced dosing regimen - as evaluated by micro computed tomography (micro-CT).

Albumin-hitchhiking: Fostering the pharmacokinetics and anticancer therapeutics.

Nanotherapeutics demonstrate poor accumulation in the tumor microenvironment due to poor extravasation and penetration into the tumor. Therapeutics such as oligonucleotides, peptides and other biologicals suffer from low systemic half-life and rapid degradation. Albumin-hitchhiking has emerged as an effective strategy to enhance tumor-specific accumulation of various therapeutics. Hitchhiking on serum albumin (SA) have shown to improve biological half-life of various therapeutics including nanocarriers (NCs), biologics, oligonucleotides, vaccines, etc. In addition, passive and active accumulation of SA-riding therapeutics in the tumor, site-specific drug release, and SA-mediated endosomal escape have improved the potential of various anticancer modalities such as chemo-, immune-, vaccine, and gene therapies. In this review, we have discussed the advantages of employing SA-hitchhiking in anticancer therapies. In addition, vaccine strategies employing inherent lymph-nodes accumulating property of albumin have been discussed. We have presented a clinical overview of SA-hitchhiked formulations along with possible bottlenecks for improved clinical outcomes. We have also discussed the role of physiologically based pharmacokinetics (PBPK) modelling for efficient characterization of anti-cancer nanotherapeutics.

Floating microspheres: Emerging delivery system for diabetes mellitus

In order to increase bioavailability, stability, and target the drug to a specific region at a predetermined rate, floating microspheres, multi-unit drug delivery systems, are designed to accomplish controlled or delayed drug administration. In clinical practise, drugs that have an upper small intestine absorption window may benefit the most from a controlled drug delivery system with an extended stomach residence period. The non-uniformity of medication absorption throughout the gastrointestinal tract and the heterogeneity of gastrointestinal (GI) transit time across and among subjects are the two key issues. The most common drug delivery systems in these applications are floating or hydrodynamically controlled. Gastro retentive medication delivery is a method of extending the length of gastric residency because it targets site-specific drug release for local or systemic effects in the upper gastrointestinal tract (GIT). Due to the uniform distribution of these multiple-unit dose forms in the stomach, which encourages more repeatable medicine absorption and a lower risk of local discomfort, floating microspheres are becoming more and more popular. Compared to single-unit dosing variants, these systems offer more benefits. The physiology of stomach emptying is briefly examined in the context of floating drug delivery systems in this paper. This review's objective is to compile the most recent research on preparation techniques and other factors that affect the functionality and characterization of floating microspheres.