In Situ Bioprinting: Process, Bioinks, and Applications.

Traditional tissue engineering methods face challenges, such as fabrication, implantation of irregularly shaped scaffolds, and limited accessibility for immediate healthcare providers. In situ bioprinting, an alternate strategy, involves direct deposition of biomaterials, cells, and bioactive factors at the site, facilitating on-site fabrication of intricate tissue, which can offer a patient-specific personalized approach and align with the principles of precision medicine. It can be applied using a handled device and robotic arms to various tissues, including skin, bone, cartilage, muscle, and composite tissues. Bioinks, the critical components of bioprinting that support cell viability and tissue development, play a crucial role in the success of in situ bioprinting. This review discusses in situ bioprinting techniques, the materials used for bioinks, and their critical properties for successful applications. Finally, we discuss the challenges and future trends in accelerating in situ printing to translate this technology in a clinical settings for personalized regenerative medicine.

Rivastigmine-DHA ion-pair complex improved loading in hybrid nanoparticles for better amyloid inhibition and nose-to-brain targeting in Alzheimer's.

Rivastigmine hydrogen tartrate (RIV-HT) is given orally for Alzheimer's disease. However, oral therapy shows low brain bioavailability, short half-life and gastrointestinal-mediated adverse effects. RIV-HT intranasal delivery can avoid these side effects, but its low brain bioavailability remains challenging. These issues could be solved with hybrid lipid nanoparticles with enough drug loading to enhance RIV-HT brain bioavailability while avoiding oral route side effects. The RIV-HT and docosahexaenoic acid (DHA) ion-pair complex (RIV:DHA) was prepared to improve drug loading into lipid-polymer hybrid (LPH) nanoparticles. Two types of LPH, i.e., cationic (RIV:DHA LPH(+ve)) and anionic LPH (RIV:DHA LPH(-ve)) were developed. The effect of LPH surface charge on in-vitro amyloid inhibition, in-vivo brain concentrations and nose-to-brain drug targeting efficiency were investigated. LPH nanoparticles showed concentration dependant amyloid inhibition. RIV:DHA LPH(+ve) demonstrated relatively enhanced Aß1-42 peptide inhibition. The thermoresponsive gel embedded with LPH nanoparticles improved nasal drug retention. LPH nanoparticles gel significantly improved pharmacokinetic parameters compared to RIV-HT gel. RIV:DHA LPH(+ve) gel showed better brain concentrations than RIV:DHA LPH(-ve) gel. The histological examination of nasal mucosa treated with LPH nanoparticles gel showed that the delivery system was safe. In conclusion, the LPH nanoparticle gel was safe and efficient in improving the nose-to-brain targeting of RIV, which can potentially be utilized in managing Alzheimer's.

Intranasal nanotherapeutics for brain targeting and clinical studies in Parkinson's disease.

Parkinson's disease (PD) is the second leading neurodegenerative disease globally, impacting the quality of life of millions of people. It is estimated that the treatment cost of PD in the USA can rise to 79 billion dollars by 2037. Limited drugs are approved by USFDA, which only provides symptomatic relief. Further, the drug efficacy is challenged due to low drug-brain concentration due to first-pass metabolism and blood-brain barrier (BBB). Intranasal drug administration can offer several advantages over systemic administration, providing efficient brain delivery. Nose-to-brain (N2B) drug delivery can enhance brain bioavailability, reduce enzymatic degradation, and reduce systemic adverse effects. However, due to poor absorption from the nasal mucosa, intranasal administration can be challenging for hydrophilic drugs. The drug mucociliary clearance, retention time, and nasal enzymatic degradation can also affect N2B drug delivery. Nanocarriers can enhance residence time, improve nasal permeation, increase brain uptake, and reduce enzymatic degradation. This review discusses the roles and applications of various N2B nanocarriers to treat PD effectively. Clinical trials of antiparkinson molecules is also covered. Lastly, safety aspects and prospects of potential nanotherapeutics for the effective treatment of PD are discussed.

Self-Assembled Lecithin-Chitosan Nanoparticles Improved Rotigotine Nose-to-Brain Delivery and Brain Targeting Efficiency.

Rotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson's disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (<1%), low aqueous solubility, and extensive first-pass metabolism. In this study, rotigotine-loaded lecithin-chitosan nanoparticles (RTG-LCNP) were formulated to enhance its nose-to-brain delivery. RTG-LCNP was prepared by self-assembly of chitosan and lecithin due to ionic interactions. The optimized RTG-LCNP had an average diameter of 108 nm with 14.43 ± 2.77% drug loading. RTG-LCNP exhibited spherical morphology and good storage stability. Intranasal RTG-LCNP improved the brain availability of RTG by 7.86 fold with a 3.84-fold increase in the peak brain drug concentration (Cmax(brain)) compared to intranasal drug suspensions. Further, the intranasal RTG-LCNP significantly reduced the peak plasma drug concentration (Cmax(plasma)) compared to intranasal RTG suspensions. The direct drug transport percentage (DTP (%)) of optimized RTG-LCNP was found to be 97.3%, which shows effective direct nose-to-brain drug uptake and good targeting efficiency. In conclusion, RTG-LCNP enhanced drug brain availability, showing the potential for clinical application.

Design, Characterization and Pharmacokinetic-Pharmacodynamic Evaluation of Poloxamer and Kappa-Carrageenan-Based Dual-Responsive In Situ Gel of Nebivolol for Treatment of Open-Angle Glaucoma.

This study developed a dual-responsive in situ gel of nebivolol (NEB), a selective ß-adrenergic antagonist. The gel could achieve sustained concentrations in the aqueous humor to effectively treat glaucoma. The gel was prepared using a combination of poloxamers (Poloxamer-407 (P407) and Poloxamer-188 (P188)) and kappa-carrageenan (κCRG) as thermo-responsive and ion-sensitive polymers, respectively. Box-Behnken design (BBD) was used to optimize the effect of three critical formulation factors (concentration of P407, P188 and κCRG) on two critical response variables (sol-to-gel transition temperature of 33-35 °C and minimum solution state viscosity) of the in situ gel. A desirability function was employed to find the optimal concentrations of P407, P188 and κCRG that yielded a gel with the desired sol-to-gel transition temperature and solution state viscosity. An NEB-loaded gel was prepared using the optimized conditions and evaluated for in vitro drug release properties and ex vivo ocular irritation studies. Furthermore, ocular pharmacokinetic and pharmacodynamics studies were conducted in rabbits for the optimized formulation. The optimized NEB-loaded gel containing P407, P188 and κCRG had a sol-to-gel transition temperature of 34 °C and exhibited minimum viscosity (212 ± 2 cP at 25 °C). The optimized NEB-loaded gel sustained drug release with 86% drug release at the end of 24 h. The optimized formulation was well tolerated in the eye. Ocular pharmacokinetic studies revealed that the optimized in situ gel resulted in higher concentrations of NEB in aqueous humor compared to the NEB suspension. The aqueous humor Cmax of the optimized in situ gel (35.14 ± 2.25 ng/mL) was 1.2 fold higher than that of the NEB suspension (28.2 ± 3.1 ng/mL), while the AUC0-∞ of the optimized in situ gel (381.8 ± 18.32 ng/mL*h) was 2 fold higher than that of the NEB suspension (194.9 ± 12.17 ng/mL*h). The systemic exposure of NEB was significantly reduced for the optimized in situ gel, with a 2.7-fold reduction in the plasma Cmax and a 4.1-fold reduction in the plasma AUC0-∞ compared with the NEB suspension. The optimized gel produced a higher and sustained reduction in the intra-ocular pressure compared with the NEB suspension. The optimized gel was more effective in treating glaucoma than the NEB suspension due to its mucoadhesive properties, sustained drug release and reduced drug loss. Lower systemic exposure of the optimized gel indicates that the systemic side effects can be significantly reduced compared to the NEB suspension, particularly in the long-term management of glaucoma.

Current clinical status of new COVID-19 vaccines and immunotherapy.

COVID-19, caused by SARS-CoV-2, is a positive-strand RNA belonging to Coronaviridae family, along with MERS and SARS. Since its first report in 2019 in Wuhan, China, it has affected over 530 million people and led to 6.3 million deaths worldwide until June 2022. Despite eleven vaccines being used worldwide already, new variants are of concern. Therefore, the governing bodies are re-evaluating the strategies for achieving universal vaccination. Initially, the WHO expected that vaccines showing around 50-80% efficacy would develop in 1-2 years. However, US-FDA announced emergency approval of the two m-RNA vaccines within 11 months of vaccine development, which enabled early vaccination for healthcare workers in many countries. Later, in January 2021, 63 vaccine candidates were under human clinical trials and 172 under preclinical development. Currently, the number of such clinical studies is still increasing. In this review, we have summarized the updates on the clinical status of the COVID-19 and the available treatments. Additionally, COVID-19 had created negative impacts on world's economy; affected agriculture, industries, and tourism service sectors; and majorly affected low-income countries. The review discusses the clinical outcomes, latest statistics, socio-economic impacts of pandemic and treatment approaches against SARS-CoV-2, and strategies against the new variant of concern. The review will help understand the current status of vaccines and other therapies while also providing insights about upcoming vaccines and therapies for COVID-19 management.

App-Based Yoga of Immortals: A Novel, Easy-to-use Intervention in the Management of Urinary Incontinence.

OBJECTIVE: To study the effectiveness Yoga of Immortals (YOI) intervention in participants with urinary incontinence (UI) of all types. YOI uniquely combines specific yogic postures, breathing exercises, sound therapy & meditation and is practiced by many for general well-being. MATERIALS AND METHODS: In this App-based cohort study, a survey was sent to the YOI app subscribers. Those who identified with UI and consented were sent the ICIQ-UI- SF (for mean symptom score & severity of UI), and the ICIQ-LUTS-QOL (for impact of UI on QOL) Questionnaires at baseline, 4, and 8 weeks. Global impression of improvement was assessed by PGI-I scale. RESULTS: 258/422 participants (18-74 years) were included and showed significant decrease in mean scores on the ICIQ-UI-SF (4.06 ± 0.24 at baseline; 2.90 ± 0.22 at 4-weeks [p ≤ 0.001] and 3.44 ± 0.23 at 8 weeks [p ≤ 0.001]) and ICIQ-LUTS-QOL (28.36± 0.74 at baseline; 24.46± 0.70 at 4-weeks [p ≤ 0.001] and 25.78± 0.70 at 8 weeks [p≤ 0.001]). Additionally, the 55-60 year subgroup also had significant decrease in mean scores on ICIQ-LUTS-QOL (25.06 ±1.20 at base line; 21.69 ± 1.07 at 4 weeks [p ≤ 0.01] and 22.28 ± 0.96 at 8 weeks [p ≤ 0.01]). CONCLUSION: YOI intervention resulted in significant improvement in mean scores on ICIQ-LUTS-QOL; ICIQ-UI-SF; frequency and severity of urinary leak; and daily life activity. Majority of the participants felt 'very much better' on PGI-scale. Being app- based, it has the added advantage of the ability to be used anytime and anywhere.

Advances in 3D bioprinting of tissues/organs for regenerative medicine and in-vitro models.

Tissue/organ shortage is a major medical challenge due to donor scarcity and patient immune rejections. Furthermore, it is difficult to predict or mimic the human disease condition in animal models during preclinical studies because disease phenotype differs between humans and animals. Three-dimensional bioprinting (3DBP) is evolving into an unparalleled multidisciplinary technology for engineering three-dimensional (3D) biological tissue with complex architecture and composition. The technology has emerged as a key driver by precise deposition and assembly of biomaterials with patient's/donor cells. This advancement has aided in the successful fabrication of in vitro models, preclinical implants, and tissue/organs-like structures. Here, we critically reviewed the current state of 3D-bioprinting strategies for regenerative therapy in eight organ systems, including nervous, cardiovascular, skeletal, integumentary, endocrine and exocrine, gastrointestinal, respiratory, and urinary systems. We also focus on the application of 3D bioprinting to fabricated in vitro models to study cancer, infection, drug testing, and safety assessment. The concept of in situ 3D bioprinting is discussed, which is the direct printing of tissues at the injury or defect site for reparative and regenerative therapy. Finally, issues such as scalability, immune response, and regulatory approval are discussed, as well as recently developed tools and technologies such as four-dimensional and convergence bioprinting. In addition, information about clinical trials using 3D printing has been included.

Black cardamom (Amomum subulatum Roxb.) fruit extracts exhibit apoptotic activity against lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried fruits of Amomum subulatum Roxb. (A. subulatum) are widely used as a spice. It is a part of official ayurvedic formulations used in folklore medicine to treat cancer.A. subulatum has been used in ayurvedic formulations to treat various lung conditions such as cough, lung congestion, pulmonary tuberculosis. The present traditional knowledge highlights the effectiveness of A. subulatum in treating cancer and its lung-specific efficacy. AIM OF THE STUDY: This study aims to investigate the cytotoxic potential of A. subulatum on the phenomenal and mechanistic level of lung cancer cells and identify the presence of A. subulatum actives. MATERIALS AND METHODS: The bioactivity of the extracts was tested using MTT assay, apoptotic assay, cell cycle analysis, superoxide production assay, reactive oxygen species (ROS) assay, and western blot analysis. Firstly, five different extracts were prepared using sequential extraction, and then screening of cell lines was performed using MTT assay. RESULTS: Lung cancer cells were selected as the most sensitive target, and dichloromethane extract (DE) was the most active extract. Annexin assay confirmed the mode of cell death as apoptosis. SubG1 peak found in cell cycle analysis substantiated this finding. ROS generation and superoxide showed association with apoptotic death. The upregulation and overexpression of cleaved poly(ADP-ribose)polymerase-1 (PARP-1) showed the failure of DNA repairing machinery contributes to apoptosis. LC-MS findings show the presence of cytotoxic actives cardamonin and alpinetin. CONCLUSIONS: In summary, this study shows the apoptosis-inducing potential of A. subulatum fruit extracts and confirms DNA damage as one of the causes of cell death. Further explorations using bio-fractionation and in-vivo studies are required to determine the most active constituents in A. subulatum.

Polymeric Hydrogels for Controlled Release of Black Tea and Coffee Extracts for Topical Applications.

Tea and coffee are popular beverages. Both are also used in topical applications, such as ultraviolet (UV) protection, anti-aging, and wound healing. However, the impact of tea and coffee extract on skin cells is minimally explored. This study investigated the direct exposure of tea and coffee extract on skin cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. It was found that direct exposure of tea and coffee to skin cells can be toxic at a high dose on prolonged exposure (72 h). Therefore, it was hypothesized that a formulation providing a controlled release of tea and coffee could improve their skin compatibility. Thermally cross-linked poly(acrylic acid) hydrogels loaded with tea and coffee extracts (with and without milk) were formulated and optimized. The release profiles of these hydrogels were studied at varying loading efficiency. Milk addition with tea extract retarded the tea extract release from hydrogel while minimally affecting the coffee release. This effect was due to the molecular interaction of tea with milk components, showing changes in size, zeta potential, and polydispersity index. The release study best fitted the Korsmeyer-Peppas release model. Skin cells exposed to tea or coffee-loaded hydrogel showed normal skin cell morphology under fluorescence microscopic analysis. In conclusion, the hydrogels controlled the tea and coffee release and showed biocompatibility with skin cells. It can potentially be used for skin applications.

Enhancement of Skin Delivery of Drugs Using Proposome Depends on Drug Lipophilicity.

The study aims to investigate the propylene glycol-based liposomes named 'proposomes' in enhancing skin permeation of drugs with different physicochemical properties. Ibuprofen, tofacitinib citrate, rhodamine B, and lidocaine were loaded into proposomes. These drug formulations were analyzed for particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro skin permeation. The confocal laser scanning microscopy was performed on skin treated with calcein and rhodamine B laden proposomes. The transdermal delivery relative to physicochemical properties of drugs such as logP, melting point, molecular weight, solubility, etc., were analyzed. We tested the safety of the proposomes using reconstructed human skin tissue equivalents, which were fabricated in-house. We also used human cadaver skin samples as a control. The proposomes had an average diameter of 128 to 148 nm. The drug's entrapment efficiencies were in the range of 42.9-52.7%, translating into the significant enhancement of drug permeation through the skin. The enhancement ratio was 1.4 to 4.0, and linearly correlated to logP, molecular weight, and melting point. Confocal imaging also showed higher skin permeation of calcein and rhodamine B in proposome than in solution. The proposome was found safe for skin application. The enhancement of skin delivery of drugs through proposomes was dependent on the lipophilicity of the drug. The entrapment efficiency was positively correlated with logP of the drug, which led to high drug absorption.

Effectiveness of App-Based Yoga of Immortals (YOI) Intervention for Insomnia in Asian Population during Pandemic Restrictions.

The coronavirus disease 2019 (COVID-19) pandemic created significant psychological challenges worldwide, including stress, emotional distress, and insomnia. In addition, social distancing, travel restrictions, and spread of disease have resulted in unique challenges, creating barriers to healthcare access. Compared to the rate prior to the COVID-19 pandemic, a significant increase in clinical insomnia rates have been reported. With well-known limitations of currently established treatments (e.g., cognitive behavioral therapy-insomnia (CBT-I), pharmacotherapy), there is a need to explore other effective and safe treatment modalities to treat insomnia, especially those that can be used remotely. The purpose of this study is to assess the effectiveness of app-based intervention to treat insomnia in the current era of the COVID-19 pandemic (using the Yoga of Immortals (YOI) app). This prospective cohort study was approved by the Institutional Review Board. All participants in this study were asked to complete an online survey including demographic data and validated Insomnia Severity Index (ISI) at baseline (15 May 2020), 4 weeks, and 8 weeks after starting the YOI intervention. Survey data was exported using Microsoft Excel. Statistical analysis was done using the GraphPad Prism 8. YOI intervention significantly improved the mean ISI scores in all categories of insomnia (severe, moderate, and subthreshold) at each follow-up (p ≤ 0.0001). The improvement was significant among all age groups and in both genders. In our study, YOI was a novel and effective intervention for improving insomnia symptoms and may be a new addition to the armamentarium of insomnia management. Being app-based, this has potential wider applicability, especially during the current COVID-19 pandemic.

Clinical therapies and nano drug delivery systems for urinary bladder cancer.

Bladder cancer is the 10th most commonly occurring malignancy worldwide with a 75% of 5-year survival rate, while it ranks 13th among the deaths occurring due to cancer. The majority of bladder cancer cases are diagnosed at an early stage and 70% are of non-invasive grade. However, 70% of these cases develop chemoresistance and progress to the muscle invasive stage. Conventional chemotherapy treatments are unsuccessful in curbing chemoresistance, bladder cancer progression while having an adverse side effect, which is mainly due to off-target drug distribution. Therefore, new drug delivery strategies, new therapeutics and therapies or their combination are being explored to develop better treatments. In this regard, nanotechnology has shown promise in the targeted delivery of therapeutics to bladder cancer cells. This review discusses the recent discovery of new therapeutics (chemotherapeutics, immunotherapeutic, and gene therapies), recent developments in the delivery of therapeutics using nano drug delivery systems, and the combination treatments with FDA-approved therapies, i.e., hyperthermia and photodynamic therapy. We also discussed the potential of other novel drug delivery systems that are minimally explored in bladder cancer. Lastly, we discussed the clinical status of therapeutics and therapies for bladder cancer. Overall, this review can provide a summary of available treatments for bladder cancer, and also provide opportunities for further development of drug delivery systems for better management of bladder cancer.

High resolution photopolymer for 3D printing of personalised microneedle for transdermal delivery of anti-wrinkle small peptide.

Acetyl-hexapeptide 3 (AHP-3) has good efficacy and safety profile as an anti-wrinkle small peptide. However, its skin permeation is poor due to its hydrophilicity and large molecular weight. 3D printing of personalised microneedles (MN), that contour to the skin surface, offers an attractive alternative for delivery for AHP-3. However, commercially available photocurable resin for 3D printing are not suitable for fabrication of drug loaded delivery systems. In this study, two liquid monomers, namely, polyethylene glycol diacrylate (PEGDA) and vinyl pyrrolidone (VP), were investigated at various proportions, for critical parameters such as mechanical strength of final polymer, rate of polymerisation, rate of swelling of final polymer, 3D printing resolution and safety profile of final polymer. The optimal resin, based on the above parameters, was that of ratio 7 VP: 3 PEGDA in weight. Drug loading into the optimal resin demonstrated that AHP-3 remained stable throughout the fabrication process and there was no effect on the physical properties of final polymer. Using a 3D scanned face model, a personalised MN patch was designed using computer aided design (CAD) software and subsequently fabricated using a Digital Light Processing (DLP) 3D printer, with the optimal resin. In vitro characterisation of fabricated MN patch demonstrated the ability to penetrate human cadaver dermatomed skin and the MN remained intact after compression. The final polymer also had minimal cytotoxicity to human dermal fibroblast. Therefore, personalised MN patch fabricated using the photopolymer can potentially be a novel approach to augment transdermal delivery of AHP-3 for effective wrinkle management.

Self-assembled lecithin-chitosan nanoparticles improve the oral bioavailability and alter the pharmacokinetics of raloxifene.

In this study, we report the development and evaluation of soy lecithin-chitosan hybrid nanoparticles to improve the oral bioavailability of raloxifene hydrochloride. The nanoparticles were formed by interaction of negatively charged soy lecithin with positively charged chitosan. The ratio of soy lecithin to chitosan was critical for the charge, and hence the size of the nanoparticles. The optimal soy lecithin to chitosan ratio was 20:1 to obtain nanoparticles with particle size of 208 ± 3 nm, a ζ-potential of 36 ± 2 mV and an entrapment efficiency of 73 ± 3%. The nanoparticles were also characterized by differential scanning calorimetry and FT-IR spectrophotometer. In-vitro drug release was assessed using dialysis bag method in pH 7.4 buffer. The drug loaded nanoparticles did not cause significant reduction in the cell viability at low doses. Pharmacokinetic studies in female Wistar rats showed significant improvement (~4.2 folds) in the oral bioavailability of the drug when loaded into nanoparticles. Further, the modified everted gut sac study showed that these nanoparticles are taken up by active endocytic processes in the intestine. The ex-vivo mucoadhesion studies proved that the nanoparticles get bound to the mucus layer of the intestine, which in turn correlates with reduced excretion of the drug in faeces. In conclusion, the proposed nanoparticles appear promising for effective oral delivery of poorly bioavailable drugs like raloxifene hydrochloride.

Oral Bioavailability Enhancement of Raloxifene with Nanostructured Lipid Carriers.

Raloxifene hydrochloride (RLX) shows poor bioavailability (<2%), high inter-patient variability and extensive gut metabolism (>90%). The objective of this study was to develop nanostructured lipid carriers (NLCs) for RLX to enhance its bioavailability. The NLC formulations were produced with glyceryl tribehenate and oleic acid. The particle characteristics, entrapment efficiency (EE), differential scanning calorimetry (DSC), in vitro drug release, oral bioavailability (in rats) and stability studies were performed. The optimized nanoparticles were 120 ± 3 nm in size with positive zeta potential (14.4 ± 0.5 mV); % EE was over 90% with the drug loading of 5%. The RLX exists in an amorphous form in the lipid matrix. The optimized RLX-NLC formulation showed sustained release in vitro. The RLX-NLC significantly (p < 0.05) enhanced oral bioavailability 3.19-fold as compared to RLX-free suspension in female Wistar rats. The RLX-NLC can potentially enhance the oral bioavailability of RLX. It can also improve the storage stability.

Proposome for transdermal delivery of tofacitinib.

Tofacitinib citrate (TC) has recently gained interest in treating skin disorders such as psoriasis, atopic dermatitis and baldness. Unfortunately, the oral administration shows side effects, such as decreased neutrophil counts. To this end, the topical delivery of TC can be used to reduce the risk associated with systemic exposure. However, TC shows minimal absorption via skin. Hence, the objective of this study is to enhance the skin delivery of TC using a non-invasive approach. The liposomes based on propylene glycol, named as proposomes, carrying TC, were studied. The vesicle characteristics and in vitro skin permeation were assessed. The proposomes enhanced the skin permeability of TC by 4-11 folds. The composition of proposomes was found to affect the skin permeation and deposition of TC. The proposomes were stable for at least 6 months. Overall, proposomes were effective for targeted topical drug delivery.

Functional Catechol-Metal Polymers via Interfacial Polymerization for Applications in Water Purification.

Phenols and polyphenols have been used as a scaffold for generating multidimensional molecular architectures via complexation with metal ions. Here, we report the synthesis and characterization of metallopolymer films from three catechol derivatives having different alkyl/aryl substituents via complexation with iron and copper ions at the organic-water interface. Such interfacial polymerization is instantaneous, one step to generate functional materials, and gives good control over the organization of repeating units along the film. The films were transferred to different substrates such as filter paper, cotton, or polyester fabrics. The films are superhydrophobic with a contact angle >160° which can be tuned by regulating the orientation of nonpolar groups at the interface during polymerization. In addition, the fabricated cloth membrane showed excellent oil/water separation efficiency of more than 99% even after 50 cycles. The polymers also showed good dye extraction capacity from aqueous solutions with fast kinetics data. Such metallopolymer networks can serve as a versatile material for applications in catalysis, protective coatings, drug delivery, water filtration membranes, and liquid separations.

Microneedles with Tunable Dissolution Rate.

Dissolvable microneedle (MN) patches have been widely investigated for transdermal drug delivery. The dissolution rate of MN controls the status of drug release from the MN, which in turn determines drug absorption through skin. However, no systematic approaches have been reported to tune the dissolution profile of dissolvable MN matrices. This is the first study to show polyvinylpyrrolidone (PVP)-based dissolvable MN patches with varying dissolution profiles when PVP is copolymerized with cellulose materials. The MN patches were fabricated through thermal curing and photolithography in tandem. The various grades of pharmaceutical cellulose, such as hydroxypropyl methylcellulose and methyl cellulose, have been investigated as dissolution modifier incorporated in the MN patches. The resultant MN patches had dissolution profiles ranging from 45 min to 48 h. The dissolution rates varied with the grades of cellulose materials. Besides dissolution examination, the MN patches were characterized for their mechanical strength, moisture absorption, and skin penetration efficiency. All of the MN patches were able to penetrate the human skin in vitro. Overall, the PVP MN patches have great potential for skin applications as drug carriers with tunable dissolution profiles.

Rapid microneedle fabrication by heating and photolithography.

Many fabrication methods for microneedle (MN) involve harsh conditions and long drying time. This study aims to fabricate a dissolving MN patch in a simple and efficient manner under mild conditions, using a combination of thermal and photo polymerisation. The MN patch was fabricated by pre-polymerisation of vinylpyrrolidone solution with heating followed by photolithography. The heating temperature and time of pre-polymer solution curing were optimized based on viscosity measurement. The MN properties including shape, size, skin penetration, dissolution, moisture absorption were determined. The fabricated MNs were sharp and consistent. The heated N-vinylpyrrolidone solution required less UV exposure time, thus reducing the total fabrication time. The percentage of MN penetration in human cadaver skin was more than 33.9%. The MN was dissolved within 1-2 min in water, or 40 min in saturated water vapor.