Sustained Drug Release Profile Research Articles

Synthesis of Titanate Nanotube for Antibacterial and Tissue Regeneration Applications

An increasingly crucial therapeutic issue revolves around treating bacterial infections in chronic skin wounds that have developed resistance to antibiotics. Despite the current advancements in diagnosis, a significant number of patients still experience therapeutic failure of anti-microbials or antibiotic treatments. In this study, sodium titanate nanotubes (Na-TiNTs) were synthesized via a straightforward hydrothermal approach to facilitate the immobilization of Gentamicin (Gn) and Phenytoin (PhT). The samples were extensively characterized using different techniques, including XRD, FTIR, SEM/EDX, TEM, TGA, and BET. The result reveals that synthesized Na-TiNTs are highly porous rods in shape, with an internal diameter of 5 nm and an outer diameter ranging from 10 to 15 nm. After 16 h of encapsulation, Gn had an encapsulation efficiency (EE%) of 80 ± 2.3 %, while PhT had 89.0 ± 3.1 %. Also, Gn and PhT were released linearly, reaching 95.3 ± 1.6 % and 97.3 ± 1.6 % after 96 h. The highest doses of Gn/Na-TiNTs and PhT/Na-TiNTs, about 500 mg/mL, reduced the cell viability value from 98.2 ± 2.2 % for the untreated cell to 85.1 ± 1.6 % and 88.3 ± 3.4 %, respectively. In addition, PhT/Na-TiNTs ZOI was 28.1 ± 2.3 and 30.1 ± 1.7 mm, andthe ZOI of Gn/Na-TiNTs was 39.0 ± 1.6 mm 45.0 ± 2.4 mm for S. aureus and E. coli, indicating that PhT had antibacterial potency comparable to the standard antibiotic but less than Gn/Na-TiNTs. In vitro wound closure of approximately 87 % for Gn/Na-TiNTs and exhibited a 95 % for PhT/Na-TiNTs after 72 h. The initial findings indicate that Gn/Na-TiNTs and PhT/Na-TiNTs exhibit a sustained drug release profile, which holds potential as a viable strategy for enhancing the antibacterial efficacy and promotewound healing.

Targeted co-delivery of FOXM1 aptamer and DOX by nucleolin aptamer-functionalized pH-responsive biocompatible nanodelivery system to enhance therapeutic efficacy against breast cancer: in vitro and in vivo.

Targeted nanodelivery systems offer a promising approach to cancer treatment, including the most common cancer in women, breast cancer. In this study, a targeted, pH-responsive, and biocompatible nanodelivery system based on nucleolin aptamer-functionalized biogenic titanium dioxide nanoparticles (TNP) was developed for targeted co-delivery of FOXM1 aptamer and doxorubicin (DOX) to improve breast cancer therapy. The developed targeted nanodelivery system exhibited almost spherical morphology with 124.89 ± 12.97 nm in diameter and zeta potential value of - 23.78 ± 3.66 mV. FOXM1 aptamer and DOX were loaded into the nanodelivery system with an efficiency of 100% and 97%, respectively. Moreover, the targeted nanodelivery system demonstrated excellent stability in serum and a pH-responsive sustained drug release profile over a period of 240 h following Higuchi kinetic and Fickian diffusion mechanism. The in vitro cytotoxicity experiments demonstrated that the targeted nanodelivery system provided selective internalization and strong growth inhibition effects of about 45 and 51% against nucleolin-positive 4T1 and MCF-7 breast cancer cell lines. It is noteworthy that these phenomena were not observed in nucleolin-negative cells (CHO). The preclinical studies revealed that a single-dose intravenous injection of the targeted nanodelivery system into 4T1-bearing mice inhibited tumor growth by 1.7- and 1.4-fold more efficiently than the free drug and the non-targeted nanodelivery system, respectively. Our results suggested that the developed innovative targeted pH-responsive biocompatible nanodelivery system could serve as a prospectively potential platform to improve breast cancer treatment.

Nanotextured and drug loaded Neovius Ti6Al4V ELI scaffolds with osteogenesis and anti-cancer potential

IntroductionThe use of Ti6Al4V for orthopedic implants though widely accepted, is 10X stiffer than bone, that leads to stress shielding and aseptic loosening. Further, oral delivery demands significantly large dosage of drugs. To address these twin challenges, we have fabricated open cell porous scaffolds capable of sustained dual drug delivery. Drug delivery from open cell porous Ti6Al4V implants is a promising approach for in situ delivery in orthopedic and dental implant applications. MethodologyIn this study, selective laser melting technology was used to fabricate open cell porous Ti6Al4V ELI scaffolds of 50 % volume fractions with Neovius architecture (NOCL). Electrochemical anodization was used to create micro and nano scale surface features for efficient drug loading. The two payloads: an osteogenic agent (Baicalein) and an anti-cancerous drug (Paclitaxel) were then loaded to different levels for differential release. An osteogenic agent was loaded in the nano reservoirs while paclitaxel was mixed with poloxamer and coated over the scaffold. ResultsThe mechanical stiffness of the designed NOCL lattices is approximately 1.29 ± 0.05 GPa, which is comparable to the human bone. This helps to reduce stress shielding effect. The scaffolds loaded with baicalein and paclitaxel yielded a sustained drug release profiles, releasing 57 % and 79 % of the pharmaceuticals over a 7-day period, respectively. Additionally, the baicalein-loaded nano reservoirs promote osteoblast differentiation in mesenchymal stem cells. As a result, bio-inspired 3D-printed open cell porous titanium scaffolds loaded with dual drugs offer a workable solution to the problems associated with orthopedic implants.

Fabrication and characterization of fish gelatin-based magnetic nanocomposite for biomedical applications.

Bionanocomposite is considered an advanced way to bridge the gap between the structural and functional material and achieve the desired properties in the nanocomposite. This present study highlighted the synthesis of fish gelatin-based magnetic nanocomposite (GMNC) using three different concentrations of gelatin (6% w/v, G12% w/v, and 18% w/v) individually, through the in situ coprecipitation method. The effect of gelatin concentration on the structural, functional, magnetic properties, and biocompatibility of the GMNC was studied successfully. This variation reduces the crystallite size from 20.8 to 12.2nm. GMNC obtained at minimum gelatin concentration (6% w/v) produced well-dispersed sphere-shaped magnetite nanoparticles with an average particle size of 33nm without aggregation. All three reported superparamagnetic behavior at 293K. It also noted the highly biocompatible and biodegradable nature of GMNC with a high magnetic response at a low magnetic field. This study reported the perspective of this functionalization method for biomedical applications, as GMNC is a potential carrier material that is easily attached to drug molecules through the free functional residues of gelatin molecules. The present study also performed the in vitro drug release behavior of 5'Fluorouracil-loaded GMNC (GF) at physiological conditions (pH 7.4 and 37°C). It indicates the prepared GF exhibits a sustained drug-release profile for up to 48h. Hence, these results strongly supported that the functionalized GMNC would be a potential carrier material for advanced drug delivery applications.

Synergism and attenuation of triptolide through prodrug engineering combined with liposomal scaffold strategy to enhance inhibition in pancreatic cancer

The prognosis of pancreatic cancer (PCa) is extremely poor because of its resistance to conventional therapies. Many previous studies have demonstrated that triptolide (TPL) has a potent tumoricidal activity on PCa. However, the clinical application of TPL in tumor therapy has been greatly limited by its poor aqueous solubility, short half-time, high toxicity and inefficient delivery. Here, through the engineering of prodrug technology combined with the nanodrug-delivery system (NDDS) strategy, we modified the main active site of TPL C14-OH by esterification reaction to obtain a highly lipophilic prodrug, and then encapsulated the drug in a phospholipid bilayer in liposomal vehicles through the thin-film hydration method for efficient delivery. A delivery system based on TPL lignocerate liposomes (TPL-LA-lip) for drug loading for targeted therapy against PCa was established. Our results showed that TPL-LA demonstrates exceptional compatibility with the phospholipid layer of liposomes, thereby enhancing drug retention in liposomal vehicle and improving tumor targeting and cellular uptake. Moreover, The system of TPL-LA-lip exhibited a sustained drug release profile in vitro, and intravenous administration significantly impedes tumor progression while reducing the toxicity of TPL in the PCa mouse model. These results demonstrated that the prodrug-loaded liposomes could significantly reduce the toxicity of TPL and enhance the biosafety. Overall, this prodrug approach is a simple and effective method to transform the highly toxic TPL into a safe and efficacious nanomedicine with excellent in vivo tolerability for PCa treatment.

Gelatin microsphere-alginate hydrogel combined system for sustained and gastric targeted delivery of 5-fluorouracil

In the current study, novel gelatin microspheres/methacrylated alginate hydrogel combined system (5-FU-GELms/Alg-MA) was developed for gastric targeted delivery of 5-fluorouracil as an anticancer agent. While water-in-oil emulsification method was used for the production of 5-FU-GELms, Alg-MA was synthesized through methacrylation reaction occurred by epoxide ring-opening mechanism. Then, 5-FU-GELms/Alg-MA hydrogel system was fabricated by the encapsulation of 5-FU-GELms into Alg-MA hydrogel network via UV-crosslinking. To evaluate applicability of fabricated 5-FU-GELms/Alg-MA as gastric targeted drug delivery vehicle, both swelling and in vitro drug release experiments were carried out at pH 1.2 medium resembling gastric fluid. Compared to drug release directly from 5-FU-GELms, 5-FU-GELms/Alg-MA hydrogel system showed more controlled and sustained drug release profile with lower amount of cumulative release starting from early stages, since hydrogel matrix created a barrier to the diffusion of 5-FU included in microspheres. Drug release kinetic results obtained by applying various kinetic models to release data showed that the mechanism of 5-FU release from 5-FU-GELms/Alg-MA hydrogel system is controlled by Fickian diffusion. All results revealed that 5-FU-GELms/Alg-MA hydrogel integrated system could be potentially utilized as gastric targeted drug carrier to enhance therapeutic efficacy and reduce systemic side effects in gastric cancer treatments for future studies.

Controlled release, chitosan-tethered luteolin phytocubosomes; Formulation optimization to in-vivo antiglaucoma and anti-inflammatory ocular evaluation

A chitosan-coated luteolin-loaded phytocubosomal system was prepared to improve the pharmacodynamic performance of luteolin in the treatment of glaucoma and ocular inflammation after topical ocular administration. Luteolin, a potent anti-oxidant herbal drug with poor aqueous solubility, was complexed with phospholipid. The prepared phytocubosomes were coated with chitosan, producing homogenously distributed nanosized particles (258 ± 9.05 nm) with a positive charge (+49 ± 6.09 mV), improved EE% (96 %), and increased concentration of encapsulated drug to 288 μg/ml. Polarized light microscopy revealed a cubic phase. Chitosan-coated phytocubosomes showed a sustained drug release profile (38 % over 24 h) and improved anti-oxidant activity (IC50 of 32 μg/ml). Ex vivo transcorneal permeation was higher by 3.60 folds compared to luteolin suspension. Irritancy tests confirmed their safety in ocular tissues after single and multiple administrations. The pharmacodynamic studies on glaucomatous rabbit eyes demonstrated 6.46-, 3.88-, and 1.89-fold reductions in IOP of chitosan-coated phytocubosomes compared to luteolin suspension, cubosomes, and phytocubosomes, respectively. Pharmacodynamic anti-inflammatory studies revealed faster recovery capabilities of chitosan-coated phytocubosomes over other formulations. Thus, chitosan-coated phytocubosomes could be a promising ocular hybrid system for delivering herbal lipophilic drugs such as luteolin.

In vitro and in vivo characterization of Miconazole Nitrate loaded transethosomes for the treatment of Cutaneous Candidiasis

This study aimed to fabricate Miconazole Nitrate transethosomes (MCZN TESs) embedded in chitosan-based gel for the topical treatment of Cutaneous Candidiasis. A thin film hydration method was employed to formulate MCZN TESs. The prepared MCZN TESs were optimized and analyzed for their physicochemical properties including particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (%EE), Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), deformability, and Transmission electron microscopy (TEM). In vitro release, skin permeation and deposition, skin irritation, antifungal assay, and in vivo efficacy against infected rats were evaluated. The optimized MCZN TESs showed PS of 224.8 ± 5.1 nm, ZP 21.1 ± 1.10 mV, PDI 0.207 ± 0.009, and % EE 94.12 ± 0.101 % with sustained drug release profile. Moreover, MCZN TESs Gel exhibited desirable pH, spreadability, and viscosity. Notably, the penetration and deposition capabilities of MCZN TESs Gel showed a 4-fold enhancement compared to MCZN TESs. Importantly, in vitro antifungal assay elaborated MCZN TESs Gel anti-fungal activity was 2.38-fold more compared to MCZN Gel. In vivo, studies showed a 1.5 times reduction in the duration of treatment MCZN TESs Gel treated animal group. Therefore, studies demonstrated that MCZN TESs could be a suitable drug delivery system with higher penetration and good antifungal potential.

4D Printable Salicylic Acid Photopolymers for Sustained Drug Releasing, Shape Memory, Soft Tissue Scaffolds.

3D printing of pharmaceuticals offers a unique opportunity for long-term, sustained drug release profiles for an array of treatment options. Unfortunately, this approach is often limited by physical compounding or processing limitations. Modification of the active drug into a prodrug compound allows for seamless incorporation with advanced manufacturing methods that open the door to production of complex tissue scaffold drug depots. Here we demonstrate this concept using salicylic acids with varied prodrug structures for control of physical and chemical properties. The role of different salicylic acid derivatives (salicylic acid, bromosalicylic allyl ester, iodosalicylic allyl ester) and linker species (allyl salicylate, allyl 2-(allyloxy)benzoate, allyl 2-(((allyloxy)carbonyl)oxy)benzoate) were investigated using thiol-ene cross-linking in digital light processing (DLP) 3D printing to produce porous prodrug tissue scaffolds containing more than 50% salicylic acid by mass. Salicylic acid photopolymer resins were all found to be highly reactive (solidification within 5 s of irradiation at λ = 405 nm), while the cross-linked solids display tunable thermomechanical behaviors with low glass transition temperatures (Tgs) and elastomeric behaviors, with the carbonate species displaying an elastic modulus matching that of adipose tissue (approximately 65 kPa). Drug release profiles were found to be zero order, sustained release based upon hydrolytic degradation of multilayered scaffolds incorporating fluorescent modeling compounds, with release rates tuned through selection of the linker species. Cytocompatibility in 2D and 3D was further demonstrated for all species compared to polycarbonate controls, as well as salicylic acid-containing composites (physical incorporation), over a 2-week period using murine fibroblasts. The use of drugs as the matrix material for solid prodrug tissue scaffolds opens the door to novel therapeutic strategies, longer sustained release profiles, and even reduced complications for advanced medicine.

Preparation and antibacterial activity of chitosan grafted cyclodextrin hydrogel loaded berberine hydrochloride using dual gelling agent

In this paper, cyclodextrin-grafted-chitosan (CD-g-CS) with different degrees of substitution (DS) was synthesized successfully by the reaction of O-p-toluenesulfonyl-β-cyclodextrin (TCD) and chitosan (CS), and a novel injectable thermosensitive hydrogel with rapid gelation was developed by physical cross-linking using dual gelling agents of αβ-glycerophosphate-sodium and hydrogen carbonate (GP-SHC). The results of 1H-NMR showed that the DS of CD-g-CS increased with the increase of TCD/CS (w/w). The influence of CD-g-CS with different DS, the concentration of SHC, and the ratio of CD-g-CS/GP-SHC (v/v) on gel time, swelling, drug release, degradation, and antibacterial activity of hydrogels prepared were studied. The results of FTIR indicated that the intermolecular interaction occurred in the hydrogel. And the hydrogel had a three-dimensional porous structure seen from SEM images. Compared with CS/GP hydrogel, the gel time of prepared hydrogel was shorter, which was less than 6 min, and the shortest gel time was 0.5 min. The prepared hydrogels had a good swelling ratio and degradable behavior. Berberine hydrochloride (BBH) was used as a model drug, and the gel showed a sustained drug release profile. In addition, the hydrogel had excellent antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Therefore the BBH@CD-g-CS/GP-SHC hydrogels had great potential in the development of biomedical drug delivery systems and antibacterial materials.

Design, development and in vitro quantification of novel electrosprayed everolimus-loaded Soluplus®/Polyvinyl alcohol nanoparticles via stability-indicating HPLC method in cancer therapy

Everolimus (RAD001) a mammalian target of rapamycin has been hampered by poor solubility, affecting its dissolution rate, a relationship that extends to low bioavailability. Nanoparticles (NP) based on Soluplus (SOL®) and Polyvinyl alcohol (PVA) was fabricated by electrospraying (ES) for the delivery of RAD001 to improve anti-tumour efficacy. Electrospraying with established experimental conditions produced PVA-SOL®-RAD001 NP with 71 nm mean diameter, smaller particle size distribution and >90 % encapsulation efficiency. Various polymer-drug concentrations exposed to various freeze–thaw (F/T) cycles were studied for NP optimisation and to enhance its mechanical properties. The optimised NP formulation demonstrated complete encapsulation as well as a sustained and pH dependent drug release profile for in vitro release test. In addition, to specifically study the degradation profile of RAD001 and to quantify RAD001 in the fabricated NP, a new HPLC method was developed and validated. The purpose and novelty of the HPLC method was also to ensure that RAD001 can be detected at low amounts where other conventional characterisation methods are unable to detect. The developed HPLC method was accurate, precise, robust and sensitive with LOD and LOQ values of 4.149 and 12.575 μg/mL. In conclusion, the novel developed HPLC system can be applied for the quantification of different chemotherapeutic agents and the novel electrosprayed hydrogel NP is a potential drug delivery system to increase solubility and bioavailability of RAD001 in cancer therapy.

Fused Deposition Modelling 3D-Printed Gastro-Retentive Floating Device for Propranolol Hcl Tablets.

Three-dimensional printing has revolutionized drug manufacturing and has provided a solution to the limitations associated with the conventional manufacturing method by designing complex drug delivery systems with customized drug release profiles for personalized therapies. The present investigation aims to design a gastric floating tablet with prolonged gastric floating time and sustained drug release profile. In the present study, a gastro retentive floating device (GRFD) was designed and fabricated using a fused deposition modelling (FDM)-based 3D printing technique. This device acts as a multifunctional dosage form exhibiting prolonged gastric retention time and sustained drug release profile with improved oral bioavailability in the upper gastrointestinal tract. Commercial polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments were used to design GRFD, which was comprised of dual compartments. The outer sealed compartment acts as an air-filled chamber that imparts buoyancy to the device and the inner compartment is filled with a commercial propranolol hydrochloride immediate-release tablet. The device is designed as a round-shaped shell with a central opening of varying size (1 mm, 2 mm, 3 mm, and 4 mm), which acts as a drug release window. Scanning electron microscope (SEM) images were used to determine morphological characterization. The in vitro buoyancy and drug release were evaluated using the USP type II dissolution apparatus. All the designed GRFDs exhibit good floating ability and sustained drug release profiles. GRFDs fabricated using PLA filament show maximum buoyancy (>24 h) and sustained drug release for up to 10 h. The floating ability and drug release from the developed devices were governed by the drug release window opening size and the filament material affinity towards the gastric fluid. The designed GRFDs show great prospects in modifying the drug release characteristics and could be applied to any conventional immediate-release product.

Preparation and characterization of ATP-loaded chitosan/alginate nanoparticles for therapeutic applications

Adenosine triphosphate (ATP) is known as an energy source and is generated by mitochondria which is the powerhouse of the cell. The ATP supplies energy through the disassociation of the phosphate group by the cellular enzymes. The extracellular ATP in the extracellular environment acts as a signaling molecule and can act as an anti-inflammatory molecule, can promote cancer progression, and also can act as a pro-inflammatory molecule. The degradation of ATP is a major disadvantage by ectonucleotidases that attenuates the therapeutic property of ATP in the extracellular environment. We have formulated chitosan/alginate nanoparticles loaded with ATP for increasing their encapsulation efficiency and for sustained drug release. This encapsulation can avoid ATP degradation from ectonucleotidases. Nanoparticle characterization by DLS, FTIR, SEM, encapsulation efficiency, and cytotoxicity assay by XTT assay and Live-dead assay was monitored for the synthesized nano formulated ATP. Our results showed that the formulated ATP-loaded chitosan/alginate nanoparticle sized about 342 nm with the optimum encapsulation efficiency of about 92.03% with a sustained drug release profile. These nano formulated ATP could be used for calorie restriction conditions where ATP can be supplied as an extracellular source for bypassing oxidative phosphorylation, and we can circumvent the oxidant production during oxidative phosphorylation. The concept of avoiding oxidative stress by bypassing oxidative phosphorylation can open an avenue for healthy aging.

Chitosan based wound dressing patch loaded with curcumin tagged ZnO nanoparticles for potential wound healing application

Microbial infection poses a significant challenge in wound healing, impeding various stages of the healing process. To address this issue, researchers have explored the potential of curcumin, a natural phytochemical known for its anti-inflammatory, antiviral, and antifungal properties. However, curcumin's limited bioavailability, stemming from poor solubility, has been a drawback. To overcome this limitation, a novel approach has been employed involving the incorporation of nano-curcumin (Cur) onto zinc oxide (ZnO) nanoparticles. The resulting composite was blended with chitosan (Chi) and polyvinyl alcohol (PVA) to create the PVA/Chi/ZnO-Cur patch, aiming to enhance both antimicrobial and wound healing activities. The patch was characterization using XRD, FTIR, SEM, and UV techniques. In vitro evaluations revealed excellent biocompatibility and hemocompatibility of the fabricated patches, along with a sustained drug release profile and significant antibacterial activity. Furthermore, an in vivo study confirmed the wound healing properties of the developed patch.

Dual functional pullulan-based spray-dried microparticles for controlled pulmonary drug delivery

Two main challenges are associated with current spray-dried microparticles for inhalation, including the enhancement of aerosolization performance of microparticles and the creation of sustained drug release for continuous treatment on-site. For achieving these purposes, pullulan was explored as a novel excipient to prepare spray-dried inhalable microparticles (with salbutamol sulphate, SS, as a model drug), which were further modified by additives of leucine (Leu), ammonium bicarbonate (AB), ethanol and acetone. It was demonstrated that all pullulan-based spray-dried microparticles had improved flowability and enhanced aerosolization behavior, with the fine particle (<4.46 µm) fraction of 42.0–68.7% w/w, much higher than 11.4% w/w of lactose-SS. Moreover, all modified microparticles showed augmented emitted fractions of 88.0–96.9% w/w, over 86.5% w/w of pullulan-SS. The pullulan-Leu-SS and pullulan-(AB)-SS microparticles demonstrated further increased fine particle (<1.66 µm) doses of 54.7 µg and 53.3 µg respectively, surpassing that (49.6 µg) of pullulan-SS, suggesting an additionally increased drug deposition in the deep lungs. Furthermore, pullulan-based microparticles revealed sustained drug release profiles with elongated time (60mins) over the control (2mins). Clearly, pullulan has a great potential to construct dual functional microparticles for inhalation with improved pulmonary delivery efficiency and sustained drug release on-site.

BOX-BEHNKEN DESIGN OPTIMIZATION OF SALICYLIC ACID LOADED LIPOSOMAL GEL FORMULATION FOR TREATMENT OF FOOT CORN

Objective: The present research is aimed to design and optimize a liposomal gel formulation of salicylic acid (SA) for enhanced drug permeation, higher skin drug retention, sustained release drug delivery and reduced side effects in the effective treatment of foot corn. Methods: Formulation designing and optimization of SA-loaded liposomes was done by box-Behnken experimental design using the three-factor, three-level approach. Phospholipid content, cholesterol content and drug content were selected as independent variables; while the critical quality attributes (CQAs) of liposomal formulation like particle size, PDI, zeta potential, entrapment efficiency and cumulative % drug release were considered as response variables. The SA-loaded liposomes were prepared by ethanol injection method and were characterized for desired CQAs. Finally, topical gel formulation of SA-loaded liposomes was developed and evaluated for drug content, homogeneity, spreadability, in vitro drug release, drug release kinetics, ex-vivo drug permeation and skin retention properties. Results: The particle size, PDI, zeta potential, entrapment efficiency and cumulative % drug release of SA-loaded liposomes was found to be 261.2 nm, 0.28, 0.7 mV, 57.53% and 99.57%, respectively. Developed topical gel formulation of SA-loaded liposomes exhibited a sustained drug release profile (64.48% cumulative release over 360 min) following Higuchi model kinetics. The developed formulation showed almost 2-fold enhanced drug permeation (i.e., 26.50%) and more than 2-fold higher drug retention (i.e., 10.90%) on porcine ear skin as compared to the plain salicylic acid gel. Conclusion: The SA-loaded liposomes and developed topical gel formulation possessed all desired CQAs. The in vitro drug release kinetics, ex-vivo drug permeation and skin retention studies confirmed the suitability of the developed formulation for topical application in the effective treatment of foot corn.

A cascade-responsive nanoplatform with tumor cell-specific drug burst release for chemotherapy.

Most of the nanomedicines can reduce the side effects of anti-tumor chemical drugs but do not have good enough therapeutic efficacy, largely due to the sustained drug release profile. It might be a promising alternative strategy to develop a cascade-responsive nanoplatform against tumor with the burst release of chemotherapeutics based on the highly efficient tumor cell targeting delivery. In this work, we constructed innovative nanoparticles (PMP/WPH-NPs) consisting of two functional polymers. PMP contained the MMP-2 enzyme sensitive linker and disulfide bond, which could respond to the tumor-overexpressing enzyme MMP-2 and high-level glutathione. While WPH promoted tumor penetration and acid-responsive drug release by modifying cellular penetrating peptides and polymerizing L-histidine. PMP/WPH-NPs exhibited outstanding features including longer blood circulation time, promoted tumor-specific accumulation, enhanced tumor penetration and efficient escape from lysosomes. Subsequently, the model drug paclitaxel (PTX), widely used in the tumor chemotherapy, was encapsulated into PMP/WPH-NPs via an emulsion solvent evaporation method. Within a short period of time, PTX-PMP/WPH-NP in simulated tumor cellular microenvironment could release 8 times more PTX than that in the physiological environment, demonstrating a good potential in tumor cell-specific burst drug release. In addition, PTX-PMP/WPH-NPs exhibited stronger anti-tumor activity than PTX in vitro and in vivo, which also had good biocompatibility according to the hemolysis assay and H&E staining. In summary, our work has succeeded in designing an original polymeric nanoplatform for programmed burst drug release based on the tailored tumor targeting delivery system. This new approach would facilitate the clinical translation of more anti-tumor nanomedicines. STATEMENT OF SIGNIFICANCE: Biomaterials responsive to the tumor-specific stimulus has conventionally used in the targeted-delivery of anti-tumor drugs. However, the levels of common stimulus are not uniformly distributed and not high enough to effectively trigger drug release. In an effort to achieve a better specific drug release and promote the chemotherapeutic efficacy, we constructed a cascade responsive nanoplatform with tumor cell-specific drug burst release profile. The tailored biomaterial could overcome the bio-barriers in vivo and succeeded in the programmed burst drug release based on the tumor cell-specific delivery of chemotherapeutics.

Microporous/Macroporous Polycaprolactone Scaffolds for Dental Applications.

This study leverages the advantages of two fabrication techniques, namely, melt-extrusion-based 3D printing and porogen leaching, to develop multiphasic scaffolds with controllable properties essential for scaffold-guided dental tissue regeneration. Polycaprolactone-salt composites are 3D-printed and salt microparticles within the scaffold struts are leached out, revealing a network of microporosity. Extensive characterization confirms that multiscale scaffolds are highly tuneable in terms of their mechanical properties, degradation kinetics, and surface morphology. It can be seen that the surface roughness of the polycaprolactone scaffolds (9.41 ± 3.01 µm) increases with porogen leaching and the use of larger porogens lead to higher roughness values, reaching 28.75 ± 7.48 µm. Multiscale scaffolds exhibit improved attachment and proliferation of 3T3 fibroblast cells as well as extracellular matrix production, compared with their single-scale counterparts (an approximate 1.5- to 2-fold increase in cellular viability and metabolic activity), suggesting that these structures could potentially lead to improved tissue regeneration due to their favourable and reproducible surface morphology. Finally, various scaffolds designed as a drug delivery device were explored by loading them with the antibiotic drug cefazolin. These studies show that by using a multiphasic scaffold design, a sustained drug release profile can be achieved. The combined results strongly support the further development of these scaffolds for dental tissue regeneration applications.

Hairy Nanocellulose-Based Supramolecular Architectures for Sustained Drug Release.

The engineering of a new type of trifunctional biopolymer-based nanosponges polymerized by cross-linking beta-cyclodextrin ethylene diamine (βCD-EDA) with bifunctional hairy nanocellulose (BHNC) is reported herein. We refer to the highly cross-linked polymerized BHNC-βCD-EDA network as BBE. βCD-EDA and BHNC were cross-linked at various ratios with the help of DMTMM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium) as a green activator in deionized water as a solvent, which resulted in different morphological shapes of BBE. Some of these structures were chiral due to cross-linked liquid crystalline structures. A comprehensive characterization study was done to show their unique morphological, structural, and dimensional properties of BBEs. Moreover, to further investigate and to confirm the surface modification of the precursors and final BBE structures, Fourier transform infrared and nuclear magnetic resonance spectroscopy, thermogravimetric analysis, Brunauer-Emmett-Teller analysis, and X-ray diffraction were applied. The hairy nanocellulose particles were considered as the backbone, and the immobilized cyclodextrin cavities can capture doxorubicin, which was used as a model drug molecule via host-guest inclusion complexation. Finally, the obtained BBE networks showed different and sustained drug release profiles and pH responsiveness. BBE biopolymers were tested as biocompatible nanocarriers for controlled release. We realize that these structures are too big for anti-cancer drug delivery by injection or oral intake, but these structures have a high potential to be applied in wound dressing and implants. They could also be used for capturing antibiotics, dyes, and organic compounds from wastewater.

Chitosan/agarose/graphene oxide nanohydrogel as drug delivery system of 5-fluorouracil in breast cancer therapy

Breast cancer refers to a very common deadly class of malignant tumors, especially in women worldwide. In the present study, a promising methodology has been developed to simultaneously improve the drug loading performance and achieve a sustained release of 5-fluorouracil (5-FU) as a model drug for breast cancer. For this purpose, a pH-sensitive and biocompatible hydrogel of chitosan/agarose/graphene oxide (CS/AG/GO) was first synthesized with glyoxal as cross-linker. 5-FU-loaded nanocomposites (NCs) of CS/AG/GO were then prepared via water-in-oil-in-water (W/O/W) emulsification technique. XRD and FTIR analyses confirmed the successful synthesis of the nanocarriers and gave insight on their crystalline structure and molecular interactions between the components. DLS demonstrated that the nanocarriers comprise nanoparticles with an average size of 197 nm and a PDI of 0.34. SEM revealed their spherical morphology and zeta potential measurements indicated an average surface charge of +23.5 mV. The drug loading and entrapment efficiencies (57% and 92%, respectively) were significantly higher than those reported previously for other nanocarriers. A very effective and sustained drug release profile was observed at pH 5.4; in 48 h, almost the entire 5-FU content was released. Moreover, effective cytotoxicity against breast cancer cell (BCC) lines (MCF-7) was observed: the cell viability upon incubation with CS/AG/GO/5-FU was about 23%, demonstrating its anti-cancer capability. Therefore, the synthesized NCs can potentially act as pH-sensitive nanovehicles for programmed release of 5-FU in breast cancer treatment.