Extended Drug Release Research Articles

Current Nanotechnological Strategies for Delivery of Anti-Retroviral Drugs: Overview and Future Prospects

Abstract: Globally, over forty million people are living with Human Immunodeficiency Viral (HIV) infections. Highly Active Antiretroviral Therapy (HAART) consists of two or three Antiretroviral (ARV) drugs and has been used for more than a decade to prolong the life of AIDS-diagnosed patients. The persistent use of HAART is essential for effectively suppressing HIV replication. Frequent use of multiple medications at relatively high dosages is a major reason for patient noncompliance and an obstacle to achieving efficient pharmacological treatment. Despite strict compliance with the HAART regimen, the eradication of HIV from the host remains unattainable. Anatomical and Intracellular viral reservoirs are responsible for persistent infection. Elimination of the virus from these reservoirs is critical for successful long-term therapy. Therefore, innovative approaches are required to design safe and effective therapies. Nanotechnology has revolutionized HIV drug delivery by addressing key challenges, including improving drug solubility, targeting specific cells, extending drug release, protecting drugs from degradation, overcoming biological barriers, enabling combination therapy, and enhancing vaccine delivery. Several nanocarrier systems, such as dendrimers, nanoemulsions, liposomes, solid nanoparticles (SLNs), and nanostructured lipid carriers, have been proposed to treat HIV infection. Additionally, nanosuspensions of antiretroviral drugs offer promising strategies for improving treatment outcomes. While these advancements have significantly improved HIV management strategies, challenges remain, including unexpected toxicity, avoiding harmful biological interactions, and costs associated with the large-scale production of nanopharmaceuticals.

Therapeutic Contact Lenses for Intraocular Drug Administration: Innovations and Applications in Treating Fungal Keratitis

This review examines the advancements in ocular medication administration, focusing on therapeutic contact lenses (TCLs) as a novel approach for treating fungal keratitis. Traditional eye Drops' bioavailability is poor due to various anatomical and physiological barriers, necessitating frequent administration and leading to poor patient compliance. TCLs offer a promising alternative, providing extended drug release, improved bioavailability, and enhanced patient comfort. This review explores different antifungal drugs, innovative methods for drug incorporation into TCLs, and their therapeutic efficacy. The potential of TCLs to revolutionize ocular drug delivery and improve treatment outcomes for fungal keratitis is discussed.

Revolutionizing Transdermal Patches: Navigating Clinical Challenges and Technological Progress

ransdermal patches, conceived to extend drug release, enhance bioavailability, and foster patient adherence, witnessed their inaugural approval by the USFDA in the 1980s. These patches, varying in size, constitute medicinal formulations with one or more active components that permeate the bloodstream through the skin. This review undertakes a comprehensive examination of recent strides in transdermal patch technology, encompassing critical facets such as their merits and demerits, advancements in microneedle technology, the evolution of transdermal patch generation, the integration of Artificial Intelligence, and the role of 3D printing technology. Additionally, the focus is placed on USFDA-approved patches. Various literature databases viz. Science Direct, PubMed, and Web of Sciences were explored for this research. The review furnished insights into the application of 3D printing technology in the fabrication of transdermal patches and disseminated information on USFDA-approved patches. The exploration delved into diverse strategies aimed at augmenting the efficiency of drug delivery and promoting patient compliance. Major transdermal products being marketed with details of their active substance have been discussed. Various applications of artificial intelligence in drug delivery have been summarized. It may be summarized that transdermal patch technology is not a thing of the past but a technology to stay and meet the demands of drug delivery in the present and future.

Preservative-free electrospun nanofibrous inserts for sustained delivery of ceftazidime; design, characterization and pharmacokinetic investigation in rabbit's eye

Ocular drug delivery presents significant challenges, attributed to the various anatomical and physiological barriers, as well as the limitations associated with conventional ocular formulations including low bioavailability, necessitating frequent dosing. The objective of the essay was to design sustained release nanofibrous inserts loaded with ceftazidime (CAZ), an antibiotic effective against gram-negative and gram-positive microorganisms, for the treatment of ocular infections. These nanofibers were fabricated using the electrospinning technique, employing biodegradable polymers such as polyvinyl alcohol (PVA), polycaprolactone (PCL) and Eudragit® (EUD). The nanofibrous inserts exhibited adequate mechanical strength for ocular use with an average diameter < 250 nm. In the initial 12-h period, a burst drug release was observed, followed by a controlled release for 120 h. Cell viability test confirmed the non-toxicity and safety of the nanofibers. The in vivo study demonstrated that the inserts sustain a drug concentration exceeding the minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa and Staphylococcus aureus for 4 and 5 days, respectively. The AUC0–120 for CAZ-PVA-PCL was reported 11,882.81 ± 80.5 μg·h/mL and for CAZ-PVA-EUD was 9649.39 ± 86.84 μg·h/mL. The nanofibrous inserts' extended drug release maintains effective antimicrobial concentrations, avoids the fluctuations of eye drops, and, by being preservative-free, eliminates cytotoxicity.

Advancing Glaucoma Therapy by Exploring the Efficacy and Potential of Brimonidine Niosomal Gel

Glaucoma is a leading cause of permanent vision loss worldwide and is characterised by progressive optic neuropathy with elevated intraocular pressure (IOP) as a major risk factor. Although successful, the current therapeutic strategies are often severely limited by their need for chronic dosing, systemic side effects and poor patient compliance. Brimonidine, an alpha-2 adrenergic receptor agonist which acts selectively, has been beneficial through its IOP-lowering effects by diminishing aqueous humor production and improving uveoscleral outflow. A novel medication delivery technology to enhance ocular bioavailability and extended drug release is brimonidine, formulated as a niosomal gel. The aim of this study is to highlight its clinical efficacy, formulation strategies and mechanism of action that significantly improved glaucoma therapy. Key studies illuminate its potential benefits in reducing dosing frequency, avoiding side effects and increasing patient compliance. Additional study and optimization required to scale-up manufacturing or ensure long-term stability. Possible future directions: combination medications and delivery systems personalized medicine possible future directions in the treatment of glaucoma might include combination medicines and personalized medicine techniques tailored to patient-specific needs. Brimonidine niosomal gel may be a new approach for glaucoma management and it can change the concept of intraocular drug delivery in the future.

A thermo-responsive chemically crosslinked long-term-release chitosan hydrogel system increases the efficiency of synergy chemo-immunotherapy in treating brain tumors

Glioblastoma multiforme (GBM) is an aggressive and common brain tumor. The blood-brain barrier prevents several treatments from reaching the tumor. This study proposes a Chemo-Immunotherapy synergy treatment chemically crosslinked hydrogel system that is injected into the tumor to treat GBM. The strategy uses doxorubicin and BMS-1 with a thermo-responsive and chemically crosslinked hydrogel for extended drug release into the affected area. The hydrogels are produced by mixing with Chitosan (Chi), modified Pluronic F-127 (PF-127) with aldehyde end group and doxorubicin and then chemically crosslinking the aldehyde and amine bonds to increase the drug retention time. PF-127-CHO/Chi, which gels at body temperatures and chemically crosslinks between PF-127-CHO and Chitosan, increases the time that the drug remains in the affected area and prevents the hydrogel from swelling and compressing surrounding tissue. The drug is released from the chemically crosslinked hydrogels, prevents tumor progression and increases survival for subjects with GBM tumors. The Synergy Chemo-Immunotherapy also allows more efficient treatment of GBM than chemotherapy. The PF-127-CHO/Chi DOX and BMS-1 group have a tumor that is 43 times smaller than the untreated group. These results show that the proposed chemically crosslinking hydrogel is an efficient intratumoral delivery platform for the treatment of tumors.

In vitro and in vivo evaluation of in situ forming polyester implants for the extended release of carvedilol.

Polyester based in situ forming implants (ISFIs) are injectable long-acting drug delivery systems that offer a wide range of unique advantages. As a result of these advantages, two relatively highmolecular weight, ester terminated grades of poly (D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) were evaluated for their ability (i) to form ISFIs loaded with carvedilol, and (ii) to control its release both in vitro and in vivo. At a polymeric concentration of 40% w/w, implant solutions were syringeable, injectable, and able to encapsulate carvedilol to a high degree (encapsulated drug% > 97%). When visualized using scanning electron microscopy (SEM), implants were found to have a dense thin surface atop porous sublayers. As for their in vitro evaluation, PLGA and PLA implants were able to maintain drug release over the course of 49 and 84 days, respectively. On the other hand, in vivo drug release from both implants was almost identical and lasted for only 42 days. This may be due to the overriding effect of the similar host environment at the injection site that diminished the effect of polymeric physiochemistry on phase inversion and drug release. Lastly, while the polymer-free drug/NMP solution completely released its drug content within the initial half hour in vitro, the formulation extended drug release in vivo. This could be due to a yet to be investigated interaction between carvedilol and NMP under in vivo conditions. These results cement the significance of formulating carvedilol loaded ISFIs for the management of chronic conditions.

Optimization and Characterization of Mucoadhesive Buccal Films using Mimosa Seed-based Natural Polymer for Controlled Drug Release: A Sustainable Approach

Background: The present study attempted to develop cost-effective, biocompatible and biodegradable mucoadhesive buccal films exploring and using Mimosa pudica seed polymer, marking its potential as a sustainable drug delivery in pharmaceutical development. Methods: The extracted polymer was characterized for solubility, viscosity, loss on drying, pH, swelling index, starch, and mucilage ingredients. Compatibility between the polymer, drug, and excipients was assessed using FTIR analysis. Buccal film trial batches were formulated using the film casting technique and were optimized using the 23 full factorial design. Optimized formulation was characterized for drug release, permeability, mucoadhesive study, similarity, and difference factor along with histological and stability study. Results: The polymer’s pH, loss on drying, swelling index, and viscosity were 6.2, 6.8%, 81.77%, and 50,000 cP respectively. FTIR studies showed the compatibility between natural polymer, the model drug metoprolol succinate, and the excipients used. The early trial batches of polymeric films showed an extended drug release comparable to the standard polymers with a good permeability flux of 0.4048 ± 0.081 mcg*cm-2*h-1. The optimized film provided a controlled release of 52.31 ± 0.035% for more than 8 h following zero order kinetics. Mucoadhesive strength was found to be 32.25 ± 0.29 g. The similarity factor f2 (90.2) and difference factor f1 (8.197) indicated no significant difference compared to the standard formulation. Histological study demonstrated the non-irritant nature of the films and stability was established from the stability studies. Conclusion: Thus, a sustainable approach using natural polymeric buccal films was found promising for mucoadhesion and controlled release.

Preclinical evaluation of a novel antibiotic-eluting BioEnvelope for CIED infection prevention

The risk of infection remains a significant concern with cardiovascular implantable electronic devices, necessitating the development of new strategies. This study explores the efficacy of a novel antibiotic-eluting biologic envelope designed to mitigate infection risk through localized antibiotic delivery while preserving the regenerative properties of biological matrix. Antibiotics, rifampin and minocycline, are released through polymer discs, ensuring extended drug release. Utilizing an established model of infection in a New Zealand White rabbit, the study assessed performance against Gram-positive bacterial strains, including common pathogens such as Staphylococcus aureus and S. epidermidis associated with CIED infections, and Gram-negative bacterial strains. Results demonstrated strong antibacterial activity, achieving complete eradication of bacterial colonies and greater than 6-log reductions in colonization for all strains. Pharmacokinetic analysis revealed sustained local antibiotic concentrations at the implantation site for up to 14 days, with minimal systemic exposure, demonstrating the advantages of localized drug delivery. Health outcomes in the antibiotic bioenvelope group were significantly improved, with no signs of infection or abnormal body temperatures, in contrast to the control group. Macroscopic examinations post-necropsy confirmed the absence of infection at the implantation sites of animals receiving the antibiotic bioenvelope. The combination of localized antibiotic delivery in a regenerative matrix positions the antibiotic bioenvelope as a promising solution for preventing CIED-related infections.

Impact of Hot-Melt Extrusion on Glibenclamide's Physical and Chemical States and Dissolution Behavior: Case Studies with Three Polymer Blend Matrices.

This research work dives into the complexity of hot-melt extrusion (HME) and its influence on drug stability, focusing on solid dispersions containing 30% of glibenclamide and three 50:50 polymer blends. The polymers used in the study are Ethocel Standard 10 Premium, Kollidon SR and Affinisol HPMC HME 4M. Glibenclamide solid dispersions are characterized using thermal analyses (thermogravimetric analysis (TGA) and differential scanning calorimetry), X-ray diffraction and scanning electron microscopy. This study reveals the transformation of glibenclamide into impurity A during the HME process using mass spectrometry and TGA. Thus, it enables the quantification of the extent of degradation. Furthermore, this work shows how polymer-polymer blend matrices exert an impact on process parameters, the active pharmaceutical ingredient's physical state, and drug release behavior. In vitro dissolution studies show that the polymeric matrices investigated provide extended drug release (over 24 h), mainly dictated by the polymer's chemical nature. This paper highlights how glibenclamide is degraded during HME and how polymer selection crucially affects the sustained release dynamics.

Bacterial nanocellulose as a simple and tailorable platform for controlled drug release

In this study we present a proof of concept of a simple and straightforward approach for the development of a Bacterial Nanocellulose drug delivery system (BNC-DDS), envisioning the local delivery of immunomodulatory drugs to prevent foreign body reaction (FBR). Inspired by the self-adhesion behavior of BNC upon drying, we proposed a BNC laminate entrapping commercial crystalline drugs (dexamethasone-DEX and GW2580) in a sandwich system. The stability of the bilayer BNC-DDS was evidenced by the high interfacial energy of the bilayer films, 150 ± 11 and 88 ± 7 J/m2 respectively for 2 mm- and 10-mm thick films, corresponding to an increase of 7.5 and 4.4-fold comparatively to commercial tissue adhesives. In vitro release experiments unveiled the tunability of the bilayer BNC-DDS by showing extended drug release when thicker BNC membranes were used (from 16 to 47 days and from 35 to 132 days, for the bilayer-BNC entrapping DEX and GW2580, respectively). Mathematical modeling of the release data pointed to a diffusion-driven mechanism with non-fickian behavior. Overall, the results have demonstrated the potential of this simple approach for developing BNC-drug depots for localized and sustained release of therapeutic agents over adjustable timeframes.

Emulsion-Based Multi-Phase Integrated Microbeads with Inner Multi-Interface Structure Enable Dual-Modal Imaging for Precision Endovascular Embolization.

Microsphere-based embolic agents have gained prominence in transarterial embolization (TAE) treatment, a critical minimally invasive therapy widely applied for a variety of diseases such as hypervascular tumors and acute bleeding. However, the development of microspheres with long-term, real-time, and repeated X-ray imaging as well as ultrasound imaging remains challenging. In this study, emulsion-based dual-modal imaging microbeads with a unique internal multi-interface structure is developed for TAE treatment. The embolic microbeads are fabricated from a solidified oil-in-water (O/W) emulsion composed of crosslinked CaAlg-based aqueous matrix and dispersed radiopaque iodinated oil (IO) droplets through a droplet-based microfluidic fabrication method. The CaAlg-IO microbeads exhibit superior X-ray imaging visibility due to the incorporation of exceptionally high iodine level up to 221 mgImL-1, excellent ultrasound imaging capability attributed to the multi-interface structure of the O/W emulsion, great microcatheter deliverability thanks to their appropriate biomechanical properties and optimal microbead density, and extended drug release behavior owing to the biodegradation nature of the embolics. Such an embolic agent presents a promising emulsion-based platform to utilize multi-phased structures for improving endovascular embolization performance and assessment capabilities.

Drug-impregnated contact lenses via supercritical carbon dioxide: A viable solution for the treatment of bacterial and fungal keratitis

Keratitis is a corneal infection caused by various bacteria and fungi. Eye drop treatment of keratitis involves significant challenges due to difficulties in administration, inefficiencies in therapeutic dosage, and frequency of drug applications. All these are troublesome and result in unsuccessful treatment, high cost, time loss, development of drug resistance by microorganisms, and a massive burden on human health and the healthcare system. Most of the antibacterial and antifungal medications are non-water-soluble and/or include toxic drug formulations. Here, the aim was to develop drug-loaded contact lenses with therapeutic dosage formulations and extended drug release capability as an alternative to eye drops, by employing supercritical carbon dioxide (ScCO2) as a drug impregnation solvent to overcome inefficient ophthalmic drug use. ScCO2, known as a green solvent, has very low viscosity which provides high mass transfer power and could enhance drug penetration into contact lenses much better with respect to drug loading using other solvents. Here, moxifloxacin (MOX) antibiotic and amphotericin B (AMB) antifungal medicines were separately loaded into commercially available silicone hydrogel contact lenses through 1) drug adsorption from the aqueous solutions and 2) impregnation techniques via ScCO2 and their efficacies were compared. Drug impregnation parameters, i.e., 8–25 MPa pressure, 310–320 K temperature, 2–16-hour impregnation times, and the presence of ethanol as polar co-solvent were investigated for the optimization of the ScCO2 drug impregnation process. The highest drug loading and long-term release kinetic from the contact lenses were obtained at 25 MPa and 313 K with 2.5 h impregnation time by using 1 % ethanol (by volume). Furthermore, antibacterial/antifungal activities of the MOX- and AMB-impregnated contact lenses were effective against in vitro Pseudomonas aeruginosa (ATCC 10145) bacteria and Fusarium solani (ATCC 36031) fungus for up to one week. Consequently, the ScCO2 method can be effectively used to impregnate commercial contact lenses with drugs, and these can then be safely used for the treatment of keratitis. This offers a sustainable delivery system at effective dosage formulations with complete bacterial/fungal inhibition and termination, making it viable for real animal/human applications.

Self-Reinforced MOF-Based Nanogel Alleviates Osteoarthritis by Long-Acting Drug Release.

Intra-articular injection of drugs is an effective strategy for osteoarthritis (OA) treatment. However, the complex microenvironment and limited joint space result in rapid clearance of drugs. Herein, a nanogel-based strategy is proposed for prolonged drug delivery and microenvironment remodeling. Nanogel is constructed through the functionalization of hyaluronic acid (HA) by amide reaction on the surface of Kartogenin (KGN)-loaded zeolitic imidazolate framework-8 (denoted as KZIF@HA). Leveraging the inherent hydrophilicity of HA, KZIF@HA spontaneously forms nanogels, ensuring extended drug release in the OA microenvironment. KZIF@HA exhibits sustained drug release over one month, with low leakage risk from the joint cavity compared to KZIF, enhanced cartilage penetration, and reparative effects on chondrocytes. Notably, KGN released from KZIF@HA serves to promote extracellular matrix (ECM) secretion for hyaline cartilage regeneration. Zn2+ release reverses OA progression by promoting M2 macrophage polarization to establish an anti-inflammatory microenvironment. Ultimately, KZIF@HA facilitates cartilage regeneration and OA alleviation within three months. Transcriptome sequencing validates that KZIF@HA stimulates the polarization of M2 macrophages and secretes IL-10 to inhibit the JNK and ERK pathways, promoting chondrocytes recovery and enhancing ECM remodeling. This pioneering nanogel system offers new therapeutic opportunities for sustained drug release, presenting a significant stride in OA treatment strategies.

Exploring MIL-68(Al) nanocarrier for melatonin delivery: probing pro-oxidant effects in cancer cells and achieving sustained drug release

This study explored the synthesis of MIL-68(Al), characterized its properties, and investigated its ability to encapsulate and release melatonin (MEL) in response to changes in pH, intending to develop a more effective drug delivery system. Analyses were directed to characterize the designed nanocarriers before and after drug loading. The drug loading efficiency (DLE) and drug loading content (DLC) of MIL-68(Al) were 78.8% and 44.0%, respectively. The extended drug release period of MEL@MIL-68(Al) was observed to exhibit a faster release under acidic conditions compared to neutral conditions. The cell treatment with free MEL, MIL-68(Al), and MEL@MIL-68(Al) was completed, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed at lung cancer A549 cells and normal fibroblastic MRC-5 cells for the cytotoxicity study. MEL@MIL-68(Al) was more cytotoxic than MIL-68(Al) in A549 cells. Analyzing reactive oxygen species (ROS) levels via fluorescent microscopic analysis showed ROS overproduction in cells treated with MEL@MIL-68(Al) in comparison to other interventions. Additionally, MEL@MIL-68(Al) modulated the protein expression levels of Nrf-2, Keap-1, and HO-1 in cells. Therefore, MEL@MIL-68(Al) exerts its potent anticancer effects via ROS overproduction and downregulation of the Nrf2/Keap-1 pathway. Therefore, this system can be a promising nanoplatform for the successful delivery of MEL and potentiating its anticancer effects.

Design and Characterisation of Curcumin-Loaded Nanostructured Lipid Carriers for Safe and Efficient Topical Drug Delivery in The Treatment of Pressure Ulcer

Pressure ulcers (PU) are chronic lesions with a high prevalence in at-risk populations. Although curcumin has various therapeutic properties, its use as a dermal therapeutic agent is limited by its poor solubility and permeability. This study aimed to develop nanostructured lipid carriers (NLCs) to facilitate the topical use of curcumin as wound healing agent in treating PU. The optimised curcumin-NLCs were characterised for their physicochemical properties, drug release, and skin permeation, while effectiveness and toxicity were investigated via cell viability, scratch assays, and an in vivo skin irritation test. The optimised curcumin-NLCs comprised 3.5% solid lipids, 1% surfactant, and 2% co-surfactant with an average particle size of 134.68±6.0 nm, polydispersity index of 0.248±0.00, zeta potential of −44.94±5.44, percentage of encapsulation efficiency of 93.42±0.32%, and drug loading of 0.11±0.00%. Curcumin-NLCs showed stable physicochemical properties and extended drug release for up to 48 h, with a cumulative release of 77.72% following a first-order kinetics. The formulation exhibited slower curcumin permeation than the free curcumin. Furthermore, the safe and non-toxic curcumin-NLCs were highly effective at 0.98 μM and showed a high rate of wound closure without skin irritation. Collectively, the NLCs developed for topical delivery of curcumin demonstrated prolonged and sustained release and improved wound healing activity, which indicates that curcumin-NLCs are a viable strategy for treating PU.

Recent Advances in Targeted Therapies for Infantile Hemangiomas.

Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage. Meanwhile, they can extend drug release times, enhance drug stability, decrease dosing frequency, and improve patient compliance. Moreover, carriers made from biocompatible materials reduced drug immunogenicity, minimizing adverse reactions. However, current targeted formulations still face numerous challenges such as the non-absolute safety of carrier materials; the need to further increase drug loading capacity; the limitation of animal hemangioma models in fully replicating the biological properties of human infantile hemangiomas; the establishment of models for deep-seated hemangiomas with high incidence rates; and the development of more specific targets or markers. In this review, we provided a brief overview of the characteristics of IHs and summarized the past decade's advances, advantages, and targeting strategies of targeted drug delivery systems for IHs and discussed their applications in the treatment of IHs. Furthermore, the goal is to provide a reference for further research and application in this field.

Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT)

There is considerable evidence from the literature that psychedelics, such as N,N-dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in vivo at sub-hallucinogenic dosages, and depending on the target indication, subjecting patients to high, bolus dosages may not be necessary. Due to rapid metabolic degradation, achieving target levels of DMT in subjects is difficult, requiring IV administration, which poses risks to patients during the intense hallucinogenic and subjective drug effects. The chemical and physical properties of DMT make it an excellent candidate for non-invasive, transdermal delivery platforms. This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioral and pharmacokinetic studies were performed with lead patch formulation (F5) in male and female Swiss Webster mice, and resulting DMT levels in plasma and brain samples were quantified using LC/MS/MS. Notable differences were seen in female versus male mice during IV administration; however, transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose. The IV half-life of DMT was extended by 20-fold with administration of the transdermal delivery system at sub-hallucinogenic plasma concentrations not exceeding 60 ng/mL. Results of a translational head twitch assay (a surrogate for hallucinogenic effects in non-human organisms) were consistent with absence of hallucinations at low plasma levels achieved with our TDDS. Despite the reported low bioavailability of DMT, the non-invasive transdermal DMT patch F5 afforded an impressive 77 % bioavailability compared to IV at two dosages. This unique transdermal delivery option has the potential to provide an out-patient treatment option for ailments not requiring higher, bolus doses and is especially intriguing for therapeutic indications requiring non-hallucinogenic alternatives.

Fabrication and optimization of extended-release beads of diclofenac sodium based on Ca++ cross-linked Taro (Colocasia esculenta) stolon polysaccharide and pectin by quality-by-design approach

The present investigation was aimed to fabricate and optimize extended-release beads of diclofenac sodium based on an ion-cross-linked matrix of pectin (PTN) and taro (Colocasia esculenta) stolon polysaccharide (TSP) with 23 full factorial design. Total polysaccharide concentration (TPC), polysaccharide ratio (PR), and cross-linker concentration ([CaCl2]) were taken as independent factors with two levels of each. Initially, TSP was extracted, purified, and characterized. Fourier-transform infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) showed drug-polymer compatibility. The study also revealed the significant positive effect of TSP on drug entrapment efficiency (DEE) and sustaining drug release. The response variables (DEE, cumulative % drug-release at 1, 2, 4, 6, and 10 h, release-constant, time for 50 % and 90 % drug release (T50%, T90%), release-similarity factor (f2), and difference factor (f1) were analyzed, and subsequently, independent fabrication variables were numerically optimized by Design-Expert software (Version-13; Stat-Ease Inc., Minneapolis). The optimized batch exhibited appreciable DEE of 88.5 % (± 2.2) and an extended-release profile with significantly higher T50%, T90%, and release-similarity factor (f2) of 4.7 h, 11.4 h, and 71.6, respectively. Therefore, the study exhibited successful incorporation of the novel TSP as a potential alternative adjunct polysaccharide in the pectin-based ion-cross-linked inter-penetrating polymeric network for extended drug release.

3D Printing of Succulent‐Inspired Microneedle Array for Enhanced Tissue Adhesion and Controllable Drug Release

AbstractControllable and long‐term release remains a great challenge in current drug delivery systems. Benefiting from their efficient drug loading and painless administration, microneedles (MNs) have emerged as a promising platform for transdermal drug delivery, while they often fail to achieve long‐term tissue adhesion and controllable extended drug release. Here, 3D printing of an innovative MN patch is presented with succulent‐inspired responsive microstructures and light‐controllable long‐term release capability. The MN exhibits a reversible shrink‐swell volume change behavior in response to surrounding humidity, which enables sufficient mechanical strength for skin penetration under the shrinkage conditions and efficient long‐term adhesion when swollen in skin tissues. Moreover, the MN patch introduces a controllable long‐term drug release system, achieved through the integration of thiolated heparin (Hep‐SH) for sustained growth factor release and graphene oxide (GO) nanosheets for controlled drug release via near infrared (NIR) laser irradiation. The MN patches with growth factor loading have good biocompatibility and can promote the proliferation, migration, and proangiogenesis of endothelial cells is further demonstrated. Thus, it is believed that such flexible MN patches can be promising candidates for controllable long‐term transdermal drug delivery as well as other related tissue engineering applications.