Sustained Drug Release Properties Research Articles

Noninvasive monitoring of bone regeneration using NaYF4: Yb3+, Er3+ upconversion hollow microtubes supporting PLGA-PEG-PLGA hydrogel

In this work, a novel injectable luminescent hydrogel composite composed of poly(l-lactide-co-glycolide)-poly(ethylene glycol)-poly(l-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer and NaYF4: Yb3+, Er3+ hollow microtubes was successfully prepared for noninvasive monitoring of bone regeneration. The incorporation of NaYF4: Yb3+, Er3+ hollow microtubes into the matrix of PLGA-PEG-PLGA resulted in the hydrogel with much rougher surface, enhanced mechanical strength, and bright upconversion luminescence. The in vitro experiments showed that the composite hydrogel possessed ideal sustained drug release property for protein drugs. Besides, it also exhibited good cellular compatibility and cell adhesion property for bone marrow mesenchymal stem cells. After loading of recombinant human bone morphogenetic protein 2 (osteogenic induction factor), the composite hydrogel was definitively implanted into the tibial defect of rats to evaluate the bone regeneration. The degradation of the composite hydrogel scaffolds and the bone defect repairing in vivo was noninvasive monitored by real-time upconversion luminescent imaging and X-ray computed tomography. The results showed that the composite hydrogel scaffold was completely degraded after 4 weeks. Moreover, a successful tibial defect repairing was realized after 6 weeks of bone regeneration. The hematoxylin-eosin staining experiments showed that the implantation and degradation of the composite hydrogel have no significant damages to the organs of heart, liver, spleen, lung and kidney during the therapeutic process, indicating its good biological safety. Our strategy provides a safety way for the noninvasive monitoring of bone regeneration, which is believed to have great potential clinical uses.

Enhancing sustained drug release property of chitosan in spheroids through crosslinking reaction and coacervation

Chitosan has not been able to be formulated as sustained-release crosslinked/coacervated drug carrier in the form of spheroids prepared by extrusion-spheronisation technique. This study re-visits chitosan spheroids and their drug (water-soluble chlorpheniramine maleate) release profiles as a function of crosslinking reaction and coacervation between chitosan, tripolyphosphate salt and alginate under the influences of pH and/or microwave irradiation. Crosslinking of chitosan or chitosan-alginate with tripolyphosphate ions, aided by acidifiers or microwave, did not retard spheroid drug release as a result of low levels of chitosan-tripolyphosphate ionic complexation, high leaching levels of sodium ions of tripolyphosphate salt as channeling agent and porous microstructure of spheroids undergoing acidification or microwave drying. Compositing of tripolyphosphate-free chitosan with alginate (weight ratio of chitosan to alginate at 0.9) however reduced the propensity of drug release, with the initial phase of drug release retardation brought about by alginate, and the late phase by chitosan. The introduction of alginate decreased the prompt disintegration tendency of chitosan spheroids. The availability of chitosan reduced the gradual erosion property of alginate. The availability of chitosan and alginate in the same matrix retained the microstructure of spheroids. The inter-spheroid coacervative bondings between the adjacent chitosan and alginate molecules resulted in spheroid aggregation, reduced the specific surface area for dissolution and further lowered the extent of drug release. Sustained-release chitosan-alginate spheroids can be prepared by extrusion-spheronisation technique through omitting crosslinking agent with channeling agent behavior, acidifier and/or microwave drying.

Chinese White Wax Solid Lipid Nanoparticles as a Novel Nanocarrier of Curcumin for Inhibiting the Formation of Staphylococcus aureus Biofilms.

Chinese white wax solid lipid nanoparticles (cwSLNs) were prepared by high shear homogenization and ultrasound methods. Using an optimized formula, spherical cwSLNs with an average particle size of 401.9 ± 21.3 nm were obtained. The cwSLNs showed high entrapment efficiency, approximately 84.6%, for loading curcumin. The curcumin loaded cwSLNs (Cur-cwSLNs) exhibited sustained drug release properties. Notably, Cur-cwSLNs had a higher drug release rate at pH 4.5 than at pH 7.4, which suggested their applicability in an acidic environment. Cur-cwSLNs were able to inhibit the growth of Staphylococcus aureus and were more effective at reducing the biofilms produced by this bacterium compared to free curcumin. This study confirmed that cwSLNs may be novel carriers for increasing the bioavailability of curcumin with the potential to inhibit the formation of S. aureus biofilms.

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full-Thickness Skin Regeneration During Wound Healing.

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full-thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid-graft-dopamine and reduced graphene oxide (rGO) using a H2 O2 /HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self-healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full-thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full-thickness skin repair.

FORMULATION AND EVALUATION OF CHITOSAN-POLYPYRROLE NANOCOMPOSITES FOR CONTROLLED RELEASE OF ANTICANCER DRUG DOXORUBICIN

Objective: The purpose of the present study was a characterization of chitosan (CS)-polypyrrole (PPY) nanocomposites for controlled release of anticancer drug doxorubicin (DOX).
 Methods: Chitosan crosslink with PPY with montmorillonite (MMT) called as (CS-PPY/MMT) were formulated using the solvent casting method. The prepared nanocomposites were characterized by X-Ray Diffraction Analysis (XRD), tensile strength, scanning electronic microscope (SEM).
 Results: The XRD result confirmed that the CS-PPY/MMT possessed crystal structure. The nanocomposites CS-PPY/MMT-4 were showed a homogenous morphology. The Water uptake and swelling ratio of the CS-PPY and CS-PPY/MMT were found to decrease with increase in the concentration of clay. Mechanical properties of the CS-PPY and CS-PPY/MMT were assessed in terms of tensile strength and extensibility using texture analyzer. Increase in tensile strength and reduction in extensibility was reported with an increase in the nanoclay content. In vitro drug release study on CS-PPY and CS-PPY/MMT indicated pronounced sustained release of doxorubicin by the incorporation of clay particles in CS-PPY/MMT. It was observed that during the first 60 min of the dissolution study, the CS-PPY/MMT-4 film showed just 79.32±0.56% drug release as while the CS-PPY-1, CS-PPY/MMT-2 and CS-PPY/MMT-3 films showed a release of 53.79±1.23%, 63.51±1.24% and 68.15±2.38% respectively.
 Conclusion: CS-PPY/MMT nanocomposite films exhibited improved mechanical and sustained drug release properties than CS-PPY. The combination of biodegradable polymeric chains and clay reinforcement can be applied to achieve the desired combination of properties of materials used as a biosensor for diverse biomedical applications.

Development of synthetic high-density lipoprotein-based ApoA-I mimetic peptide-loaded docetaxel as a drug delivery nanocarrier for breast cancer chemotherapy

In this study, a synthetic high-density lipoprotein (sHDL), peptide-based nanocarrier loaded with docetaxel (DTX) was constructed, against breast cancer. The thermodynamic and molecular dynamic analyses were conducted to examine the stability of nanoparticles synthesized from mimetic peptide 5 A and various types of phospholipids. Furthermore, the cellular uptake and in vivo fluorescence imaging analysis experiments, with scavenger receptor B-I (SR-BI) were carried out to examine the tumor-targeting ability of sHDL. The nanoparticles were investigated for their pharmacodynamic and cytotoxic effects to show their effectivity as anti-tumor agents. The results showed that the synthesized sHDL nanoparticles exhibited a high payload of DTX, sustained drug release properties, and excellent biocompatibility. Moreover, DTX-sHDL nanoparticles enhanced the uptake of DTX, increased the cytotoxicity against MCF-7 cells, and reduced the off-target side-effects to normal cells. Finally, experiments in 4T1 cell line-bearing mice indicate that inhibition of tumor growth by DTX-sHDL nanoparticles was superior to that of free DTX group. Thus, the sHDL nanoparticles are a promising drug delivery vehicle for improving the efficacy of anti-cancer drugs.

Poly-allylamine hydrochloride and fucoidan-based self-assembled polyelectrolyte complex nanoparticles for cancer therapeutics.

Herein, we fabricated the novel drug delivery system based on the self-assembly of two polyelectrolytes, poly-allylamine hydrochloride (PAH) and fucoidan, as the polycation and polyanion, respectively, under mild conditions for cancer therapeutics. Furthermore, the designed polyelectrolyte complex nanoparticles as well as the methotrexate (MTX) disodium salt-loaded composites were systematically characterized using various techniques. The MTX loading in the nanoparticles was confirmed by zeta potential values that changed from -36.2 ± 2.2 to -28.3 ± 3.1 mV at a loading amount of 13.3 ± 1.2%. Furthermore, the obtained eventual particle sizes of nanoparticles were various with different concentrations and ratios of polyelectrolytes. The particle size also has increased from 130 ± 2.6 to 162.9 ± 2.3 nm after loading MTX. The drug release investigations in vitro at a pH value of 6.0 (acid environment) showed that the release of MTX was sustained in the conditions provided. Finally, we investigated the anticancer efficacy of MTX-loaded nanoparticles on MCF-7 cells and HeLa cells and the satisfactory results were obtained. Together, these self-assembled PAH/fucoidan nanoparticles with sustained drug release property will become the promising delivery system for cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 339-347, 2019.

Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication

Glaucoma treatment with ocular medications requires overcoming the corneal barrier to drug penetration. Liposomes have a great corneal penetration ability and affinity while suffering from poor stability and low entrapment of hydrophilic drugs accompanied by rapid drug release. This work aims to develop a new, effective and stable glaucoma medication with sustained drug release properties; Timolol maleate gelatinized core liposomes. A full factorial design was utilized to study the effects of three formulation variables on drug loading and vesicle particle size. Vesicles were prepared by the thin-film hydration method, and characterized for in-vitro drug release and stability. Intra-ocular pressure (IOP) reduction was evaluated in-vivo on glaucomatous rabbit’s eyes. The safety profile was assessed using histopathological examinations. Gelatin significantly increased the drug entrapment percentage reaching 50% with a particle size of 38.81 µm. Sustained drug release was recorded compared to a marketed product and to a conventional liposomal formulation. The prepared vesicles caused the highest reduction in IOP accompanied by safe histological findings. This work provided a new, safe and effective ocular glaucoma medication; Timolol maleate gelatinized core liposomes, solving the main problems of ocular liposomal formulations of hydrophilic drugs, suitable for the pharmaceutical industry and comprising abundant and relatively cheap components.

NEWER OPHTHALMIC IN SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE: OPTIMIZATION USING BOX BEHNKEN STATISTICAL DESIGN

Objective: The present research work aims at describing the formulation and evaluation of the ocular delivery system of moxifloxacin hydrochloride (MH) based on the concept of ion sensitive in situ gelations.Methods: In situ gel was prepared by a hot method using 0.6% of gelrite, 0.25% hydroxypropylmethylcellulose (HPMC K4M) and 0.023% tamarind gum as bioadhesive polymers for sustained drug release. Optimization was done by Box Behnken Design with different concentration of gelrite (X1), HPMC K4M (X2) and tamarind gum (X3) as independent variables. In situ gel was optimized based on mucoadhesion index (Y1), Gel strength (Y2) and in vitro drug release (Y3). Influence of the quantitative variable on the dependent variable was predicted by a polynomial equation.Results: Infrared spectroscopy excluded any interaction between drug and excipients. The selected independent variables significantly influenced the responses and were able to sustain the drug release. The prepared gel with a pH of 6.8 to 7.4 exhibited non-newtonian flow with no ocular irritation. The formulation remained stable with no change in pH and viscosity after 30 d of stability study.Conclusion: Thus, moxifloxacin hydrochloride (MH) in situ gel is a viable alternative to a conventional delivery system with the properties of sustained drug release, prolonged ocular retention, and improved corneal penetration.

Formulation and Evaluation of Chitosan-Polyaniline Nanocomposites for Controlled Release of Anticancer Drug Doxorubicin

In this present work, chitosan (CS) crosslink with polyaniline (PANI) with montmorilonite (MMT) called as (CSPANI/MMT) and CS crosslink with PANI without MMT called as (CS-PANI) were prepared by employing the solution casting method. Further the formation of nanocomposites CS-PANI/MMT and CS-PANI were investigated using XRD, FTIR, SEM and tensile strength. Water uptake and swelling ratio of the CS-PANI and CS-PANI/MMT were found to decrease with increase in concentration of clay. Mechanical properties of the CS-PANI and CS-PANI/MMT were assessed in terms of tensile strength and extensibility using texture analyzer. Increase in tensile strength and reduction in extensibility was reported with increase in the nanoclay content. In vitro drug release study on CS-PANI and CS-PANI/MMT indicated pronounced sustained release of doxorubicin by the incorporation of clay particles in the CS polymer matrix. Overall CSPANI/MMT nanocomposite films exhibited improved mechanical and sustained drug release properties than CS-PANI.

AgCa-PLGA submicron particles inhibit the growth and colonization of E. Faecalis and P. Gingivalis on dentin through infiltration into dentinal tubules

Eliminating the infection from root canals and periodontal tissues of human teeth as well as the repair of infected periodontal bone has been a great challenge. Poly(lactide-co-glycolide) (PLGA) particles have been used for drug delivery due to their biodegradability, sustained drug release and nontoxic properties. As silver ions (Ag+) exhibit strong antibacterial ability and calcium ions (Ca2+) are essential for hard tissue regeneration, the Ag+ and Ca2+ were encapsulated into the PLGA particles to form AgCa-PLGA submicron particles. The physico-chemical properties, ion release, cytotoxicity, ability to infiltrate dentinal tubules, antibacterial effects against Enterococcus faecalis (E. faecalis) and Porphyromonas gingivalis (P. gingivalis) in either planktonic or biofilm forms on dentin as well as in vitro mineralization ability were investigated. Results showed that Ag+ and Ca2+ were encapsulated into the AgCa-PLGA particles, which could release both Ag+ and Ca2+ over 30 days and exhibited strong antibacterial effects against E. faecalis and P. gingivalis. AgCa-PLGA particles could infiltrate into dentinal tubules by ultrasonic activation and inhibit the colonization of E. faecalis and P. gingivalis on dentin. AgCa-PLGA particles showed no cytotoxicity and induced hydroxyapatite (HA)-like crystal formation. AgCa-PLGA submicron particles could become a biomaterial for both infection control and hard tissue regeneration in dentistry and other related medical areas.

Novel combination proliposomes containing tobramycin and clarithromycin effective against Pseudomonas aeruginosa biofilms

Tobramycin (TOB) and clarithromycin (CLA) can potentially be used synergistically for the treatment of respiratory infections caused by Pseudomonas aeruginosa (P. aeruginosa) in cystic fibrosis (CF) patients. This study aimed to develop a novel combination proliposome formulation (TOB/CLA-CPROLips) containing both hydrophilic TOB and hydrophobic CLA via a core-carrier approach. The combination proliposomes were produced by spray drying a suspension comprising spray-driedmannitol (SD-MAN, 0.45%) and spray-dried tobramycin (SD-TOB, 0.05%) particles suspended in an ethanolic lipid solution of CLA (0.05%). The lipid layer coated on the surface of the dry proliposome particles conferred moisture protection and sustained drug release properties in comparison to the pure drugs. The optimized TOB/CLA-CPROLips formulation was stable after 3 months of storage at 60% relative humidity (RH) and 25 °C. The combination drug proliposomes showed a synergistic antimicrobial activity against planktonic cells and biofilm cultures of P. aeruginosa. In conclusion, the core-carrier method coupled with spray-drying provided a novel approach for the preparation of combination antibiotics proliposomes.

Rheological and controlled release properties of hydrogels based on mushroom hyperbranched polysaccharide and xanthan gum

A hyperbranched polysaccharide, coded as TM3a, was extracted from the Pleurotus tuber-regium sclerotia. TM3a was hybridized with xanthan gum (XG) by chemical crosslinking using sodium trimetaphosphate (STMP) to obtain new hydrogels with self-healing and release-controlled properties. The oscillatory rheological measurements indicated that chemically crosslinking was happened immediately on mixing STMP solutions into the XG-TM3a solutions, and the crosslinked network developed slightly as time increased. The resultant hydroges were disturbed into the loose structures and regrouped the microstructure in 2 min when a large and a small amplitude oscillation were applied in turn, suggesting a self-healable property. The XG-TM3a-STMP hydrogels exhibited shear-thinning behavior with yield stress. The storage modulus of the XG5-TM3a-STMP hydrogel was 445.2 Pa at 1% strain and 243.3 Pa at 100% strain, and yield stress was 160.6 Pa, which was higher than the corresponding value of the XG5-STMP hydrogel. The morphological observation indicated the aggregates of double helical XG chains exhibited directional arrangement, and were combined with the TM3a aggregates to constitute a network of hierarchical structures. The hybrid hydrogels with enhanced mechanical properties displayed good drug loading efficiencies and sustained drug release properties.

Harnessing the Noncovalent Interactions of DNA Backbone with 2D Silicate Nanodisks To Fabricate Injectable Therapeutic Hydrogels.

Injectable hydrogels present several advantages over prefabricated scaffolds including ease of delivery, shear-thinning property, and broad applicability in the fields of drug delivery and tissue engineering. Here, we report an approach to develop injectable hydrogels with sustained drug release properties, exploiting the chemical nature of the DNA backbone and silicate nanodisks. A two-step gelation method is implemented for generating a combination of noncovalent network points, leading to a physically cross-linked hydrogel. The first step initiates the development of an interconnected structure by utilizing DNA denaturation and rehybridization mechanism to form hydrogen bonds between complementary base pairs of neighboring DNA strands. The anisotropic charge distribution of two-dimensional silicate nanodisks (nSi) makes them an active center in the second step of the gelation process. Silicate nanodisks create additional network points via attractive electrostatic interactions with the DNA backbone, thereby enhancing the mechanical resilience of the formulated hydrogel. The thermally stable hydrogels displayed an increase in elasticity and yield stress as a function of nSi concentration. They were able to form self-supporting structures post injection due to their rapid recovery after removal of cyclic stress. Moreover, the presence of nanosilicate was shown to modulate the release of a model osteogenic drug dexamethasone (Dex). The bioactivity of released Dex was confirmed from in vitro osteogenic differentiation of human adipose stem cells and in vivo bone formation in a rat cranial bone defect model. Overall, our DNA-based nanocomposite hydrogel obtained from a combination of noncovalent network points can serve as an injectable material for bone regeneration and carrier for sustained release of therapeutics.

Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies.

Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition. Moreover, the PPSG exerted a low cytotoxicity in L929 cells and HUVECs, suggesting the biocompatibility of PPSG. A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo, revealing its sustained and controlled drug release property. Most importantly, in cyclophosphamide-induced immunosuppressive rats, a single dose of TP5 PPSG (15 mg/kg, sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio; such an immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (0.6 mg/kg per day, sc) for 14 consecutive days. Thus, TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple manufacture process, good biocompatibility and long-lasting immunomodulatory efficacy, which could greatly improve patient compliance.

Injectable polysaccharide hydrogel embedded with hydroxyapatite and calcium carbonate for drug delivery and bone tissue engineering

To meet the progressive requirements for bone regeneration purpose, injectable hydrogels have attracted increasing attention in tissue regeneration and local drug delivery applications. In this study, we report a facile method to prepare injectable and degradable polysaccharide-based hydrogels doubly integrated with hydroxyapatite (HAp) nanoparticles and calcium carbonate microspheres (CMs) under physiological condition. The mechanism of cross-linking is attributed to the Schiff-base reaction between amino and aldehyde groups of carboxymethyl chitosan (CMCS) and oxidized alginate (OAlg), respectively. Synchronously, tetracycline hydrochloride (TH) loaded CMs were fabricated by the precipitation reaction with an average diameter of 6.62 μm. To enhance bioactive and mechanical properties, nano-HAp and CMs containing TH were encapsulated into the polysaccharide-based hydrogel to form injectable gel scaffolds for imitation of bone niche. The gelation time, morphology, mechanical properties, swelling ratio and in vitro degradation of the gel scaffolds could be controlled by varying HAp and CMs contents. Moreover, the composite gel scaffolds had good sustained drug release and antibacterial properties, as confirmed by drugs release calculation and antibacterial evaluation. In addition, the gel scaffolds were found to be self-healing due to dynamic equilibrium of the Schiff-base linkages. These results suggested that the prepared composite gel scaffolds hold great potential for drug delivery and regeneration of irregular bone defects.

Hierarchical self-assembled hollow hydroxyapatite flower microspheres containing terpene functional groups for efficient drug loading and pH-responsive drug release

In this paper, we fabricated hierarchical self-assembled hollow rose-like flower microspheres (HRFM) and hollow burr-like flower microspheres (HBFM) hydroxyapatite (HAP) using dehydroabietyl phosphate tri-ester (DDPT) as an organic phosphorus source, a regulating agent, and a soft template simultaneously via a one-step solvothermal method. The HBFM and HRFM have been explored for their application in drug delivery, using doxorubicin (DOX) as a drug model. The formation mechanisms of HRFM and HBFM were proposed on the basis of the electrostatic potential diagrams and self-assembled behavior of DDPT organic molecule. After the rosin-based terpene functional groups were incorporated, both HRFM and HBFM exhibited low cytotoxicity against Hela cell, pH-dependent sustained drug release properties, and high drug loading capacity. The drug-loading capacities of HBFM and HRFM were 116.6 mg g−1 and 148.3 mg g−1, respectively. Thus, the as-prepared HRFM and HBFM are promising for the applications in drug delivery.

Lamotrigine loaded poly-ɛ-(d,l-lactide-co-caprolactone) nanoparticles as brain delivery system

Management of epilepsy requires brain delivery therapy, therefore, this study was aimed to prepare lamotrigine loaded poly-ɛ-(d,l-lactide-co-caprolactone) (PLCL) nanoparticles using spontaneous emulsification solvent diffusion method. Nanoparticles for brain delivery required to have a particle size <200 nm, polydispesity index <0.2 and a sustained drug release properties. For such aim different factors were considered in preparing the nanoparticles as PLCL monomers' ratio, type of organic solvent used to prepare the nanoparticles, amount of PLCL and Pluronic®F127 in the nanoparticles. Prepared nanoparticles were characterized for their shape, particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading capacity, process yield and in-vitro drug release pattern. The in-vivo investigation for brain delivery of selected nanoparticles delivered by intravenous route was investigated in rats and compared to that for oral tablet. The obtained nanoparticles were spherical in shape. The amount of surfactant and PLCL affected the properties of the obtained nanoparticles. Using a mixture of organic solvent in preparing the nanoparticles improved its properties. The nanoparticles prepared using PLCL with monomers' ratio of 25:75, had particle size value of 125 nm, polydispersity index value of 0.184, zeta potential value of −39 mV and encapsulation efficiency value of 99%, was selected to study their efficacy to deliver the drug to the brain. The tested nanoparticles showed higher values of Tmax, Cmax, AUC, and MRT in homogenized rat brain, compared to oral lamotrigine tablet, while the bioavailability of the oral tablet was higher in rat plasma compared to that for the nanoparticles. This reflects that brain was the main distribution site for tested nanoparticles, and plasma was the main distribution site for oral tablets. This confirms the goal of the selected formulation as brain delivery nanoparticles.

Robust microfluidic construction of hybrid microfibers based on konjac glucomannan and their drug release performance.

The exploration of methods to produce a novel wound dressing with sustained drug release properties in ultrasmall scales is of great scientific and technological interest. Herein, we propose konjac glucomannan/polyvinylidene fluoride (KGM/PVDF) hybrid microfibers having hydrophilic and hydrophobic segments based on microfluidic-oriented core–sheath composite microfibers, where the KGM/PVDF hybrid microfibers are wrapped in situ in CH3OH. The morphology of KGM/PVDF microfibers is uniform, smooth, and crack-free. Enrofloxacin (Enro) is loaded onto the microfibers as a representative cargo to test their release performance. The KGM/PVDF/Enro microfibers show sustained drug release performance (13 days), excellent heat resistance, antibacterial activity and promotion of wound healing. This study is an avenue toward the microfluidic design of hydrophilic/hydrophobic hybrid microfibers as wound dressings, and it will guide the development of next-generation wound dressing.

Ionically cross-linked chitosan–halloysite composite microparticles for sustained drug release

AbstractThis study investigated the potential of halloysite nanotubes (HNTs) to improve the sustained release properties of chitosan (CS) microparticles cross-linked ionically with tripolyphosphate (TPP). Composite CS-HNTs microparticles were obtained by a simple and eco-friendly procedure based on a coaxial extrusion technique. Prior to encapsulation, a water-soluble model drug, verapamil hydrochloride (VH), was adsorbed successfully on HNTs. The microparticles were characterized by optical microscopy, Fourier transform infrared (FTIR) spectroscopy, differential thermal analysis/ thermogravimetric analysis (DTA/TG) and evaluated for encapsulation efficiency and drug-release properties. The composite particles had a slightly deformed spherical shape and micrometric size with average perimeters ranging from 485.4 ± 13.3 to 492.4 ± 11.9 μm. The results of FTIR spectroscopy confirmed non-covalent interactions between CS and HNTs within composite particle structures. The DTA and TG studies revealed increased thermal stability of the composite particles in comparison to the CS-TPP particles. Drug adsorption on HNTs prior to encapsulation led to an increase in encapsulation efficiency from 19.6 ± 2.9 to 84.3 ± 1.9%. In contrast to the rapid release of encapsulated model drug from CS-TPP microparticles, the composite CS-HNTs microparticles released drug in a sustained manner, showing the best fit to the Bhaskar model. The results presented here imply that HNTs could be used to improve morphology, encapsulation efficiency and sustained drug-release properties of CS microparticles cross-linked ionically with TPP.