Blend Microspheres Research Articles

High Q Ultra‐Low Threshold Lasing in Conjugated Polymer Blend Microspheres Promoted by FRET

AbstractConjugated polymer (CP) based microspheres of very high definition and outstanding photonic and luminescent properties are prepared by a technique based on slow solvent‐controlled diffusion into micelles formed by the surfactant cetyl(trimethyl)ammonium bromide (CTAB). Poly[(9,9‐di‐n‐octylfluorenyl‐2,7‐diyl)‐alt‐(benzo[2,1,3]thiadiazol‐4,8‐diyl)] (F8BT) and mixtures of F8BT with poly[2‐methoxy‐5‐(2’‐ethylhexyloxy)‐1,4‐phenylene vinylene (MEH‐PPV) are used for this purpose. Microspheres with diameters between 1 and 10 µm are obtained and structural characterization by AFM and SEM demonstrate good sphericity and low surface roughness. Correspondingly, spontaneous emission of the spheres exhibits Mie resonances of high quality factor (Q > 1800), appropriately reproduced employing standard Mie theory. Upon pumping the microspheres with a pulsed Nd:YAG laser operating at 355 nm lasing at low threshold fluences (≈ 4 µJ cm−2) is obtained with instrumentally limited linewidths corresponding to Q > 18000. Lasing in microspheres composed of blends of both CPs coupled by Förster resonant energy transfer (FRET), on the other hand, is observed at extremely low threshold fluences down to ≈ 0.5 µJ cm−2. Spherical structures based on appropriate blends of CPs are therefore promising candidates in the search for low‐threshold organic microlasers excited by light‐emitting diodes or diode lasers or for ultrasensitive optical sensing.

Formulation and Characterization of Blend Microspheres of Anti Diabetic Drug Glimepiride

The objective of the present investigation was to prepare polymeric blend microspheres of glimepiride for improving its half-life using chitosan and gelatin as the two polymers for preparing the blend. The blend microspheres of chitosan and gelatin were prepared by using different ratios of both the polymers as well as cross-linking agent, glutaraldehyde (GA), by emulsion cross-linking method. The optimum formulation was one which exhibited the lowest particles size and it was used to load glimepiride (20% by weight) of the polymers. The glimepiride loaded blend microspheres were evaluated for yield, drug polymer interaction, entrapment efficiency, surface study and in vitro release. The particle size of the blend microspheres was found to be in the range of 126.8 µm to 371.3 µm. The lowest particle size (126.8 ± 6.11 µm) was obtained in AF5 containing 50% of gelatin and 50% of chitosan. The FTIR spectra of the physical mixture of glimepiride, gelatin and chitosan displayed all the characteristic peaks of glimepiride, thus indicating that no incompatibility was present between the drug and the polymer. The SEM image of the drug loaded blend microsphere revealed spherical particles of irregular size with smooth surface. The average particles size of the glimepiride loaded blend microspheres was obtained to be 131.4 ± 9.7 µm with a yield of 91.6% by weight of the drug and polymers used for formulation of the microspheres. It was found that 82.4 ± 6.8% of glimepiride was found to be entrapped in the particles. The results of the in vitro release studies of the glimepiride loaded blend microsphere revealed that 71.49 ± 0.74 % glimepiride was released from the particles at the end of 12th hour of study.

Formulation and evaluation of 6-thioguanine-loaded gum rosin/ poly(ethylene oxide) blend microspheres for controlled release applications

This study focuses on the design, development, and in vitro evaluation of blend microspheres composed of gum rosin (GR) and poly(ethylene oxide) (PEO) by the water-in-oil emulsion solvent evaporation method for controlled release of 6-thioguanine (6-TG), an anticancer drug. By analyzing the microspheres by Fourier transform infrared spectroscopy, the chemical interactions between the polymers and the drug were explored. The results of the DSC analysis confirmed the drug was molecularly dispersed after loading into the polymer matrix. By scanning electron microscopy (SEM), it was confirmed that the microspheres were spherical. X-ray diffraction was used to analyze the crystal structure of the drug before and after encapsulation.In vitro release studies revealed that the release rate varied with the pH of buffer media, polymer ratio, drug loading amount, and observed release rate over 18 h. In vitro release results confirm that the developed microspheres are suitable for delivery of bioactive agents at intestinal pH (7.4). Based on the results, the developed blend microspheres were found to be economically and industrially feasible by applying a systematic formulation approach.

Blend microspheres of poly (glycolide-co-ε-caprolactone) and ethyl cellulose for the controlled release of 5-fluorouracil

Blend microspheres of poly (glycolide-co-ε-caprolactone) and ethyl cellulose for the controlled release of 5-fluorouracil

Chitosan-tripolyphosphate nanoparticles encapsulated rutin targeting bacterial growth inhibition and its cytotoxicity on PANC-1 pancreatic adenocarcinoma cell

Interpenetrating polymer network of cross-linked blend microspheres for controlled release of Acebutolol HClP. Ramakrishna, B. Mallikarjuna, A. Chandra Babu, P. Sudhakar, K. Chowdoji Rao, M.C.S. Subha

Assessment of temperature-sensitive properties of ionically crosslinked sodium alginate/hydroxypropyl cellulose blend microspheres: preparation, characterization, and in vitro release of paracetamol

Today, polymer systems can be formed to respond to single stimuli or multiple stimuli by changing their properties. The use of these systems, which are designed to be sensitive to stimuli, is expanding in a wide range of applications. Herein, microspheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn2+ ions. FTIR, DSC, TGA, SEM, and particle size measurements were used to describe the blend microspheres. Low critical solution temperatures (LCST) of polymer blends at different ratios were determined and the biggest change according to the LCST value of HPC was found to be approximately 1–2 °C lower than 41 °C in microspheres with a NaAlg/HPC ratio of 50/50. In vitro release experiments of paracetamol from microspheres were carried out in a gastrointestinal tract simulation environment at two different temperatures (37 °C and 47 °C). From the release profiles, paracetamol release varied depending on the NaAlg/HPC ratio, the paracetamol content in the microspheres, the exposure time to Zn2+ ions, and the pH of the medium. Among the microsphere formulations, the highest entrapment efficiency was 57.86%, obtained for B7 formulation microspheres with a NaAlg/HPC ratio of 70/30, a paracetamol loading percentage of 20%, and a crosslinking time of 5 min. RESEARCH HIGHLIGHTS Microspheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn2+ ions. LCST values of the microspheres with a NaAlg/HPC ratio of 50/50 were significantly lower by 1–2 °C than the LCST value of HPC, and the release results supported the temperature sensitivity of the microspheres. Among the microsphere formulations, the highest entrapment efficiency was 57.86% obtained for B7 formulation microspheres. These microspheres can be used as a temperature-sensitive drug delivery system in the biomedical field and also as an encapsulation system of cancer drugs for cancer treatment modalities such as hyperthermia.

PLA-PCL microsphere formulation to deter abuse of prescription opioids by smoking

Opioids are commonly prescribed across the United States (US) for pain relief, despite their highly addictive nature that often leads to abuse and overdose deaths. Abuse deterrent formulations (ADFs) for prescription opioids make the non-therapeutic use of these drugs more difficult and less satisfying. Although approximately one-third of surveyed abusers in the US reported smoking opioids, to our knowledge, no commercialized ADF effectively prevents opioid smoking. Here, we report a novel approach to deter smoking of a model prescription opioid drug, thebaine (THB), by using polymer blend microspheres (MS) comprising polylactic acid (PLA) and polycaprolactone (PCL). We utilized high-performance liquid chromatography (HPLC) and thermogravimetric analysis (TGA) to test the ability of PLA-PCL MS to limit the escape of vaporized THB. Additionally, we compared the abuse-deterrent potential of PLA-PCL MS to that of activated carbon (AC) and mesoporous silica (MPS), two materials with excellent drug-adsorbing properties. Our MS formulation was effective in reducing the amount of both active drug and thermal degradation products in the vapor generated upon heating of THB. These results support that PLA-PCL microspheres can be co-formulated in a tablet with common prescription opioids to deter their abuse via the smoking route.

Chitosan and oral mucosal wound healing in dentistry—Journey from non-patented to patent introspection from 2010–202

Interpenetrating polymer network of cross-linked blend microspheres for controlled release of Acebutolol HClP. Ramakrishna, B. Mallikarjuna, A. Chandra Babu, P. Sudhakar, K. Chowdoji Rao, M.C.S. Subha

Synthesis and characterization of temperature-sensitive microspheres based on acrylamide grafted hydroxypropyl cellulose and chitosan for the controlled release of amoxicillin trihydrate

This study deals with the preparation of temperature-sensitive chitosan/hydroxypropyl cellulose-graft-polyacrylamide (CS/HPC-g-PAAm) blend microspheres as a controlled drug release system. For this purpose, HPC-g-PAAm copolymers of hydroxypropyl cellulose (HPC) with acrylamide (AAm) were synthesized using cerium (IV) ammonium nitrate as initiator. The HPC-g-PAAm copolymers were characterized by using Fourier transform infrared spectroscopy (FTIR), elemental analysis, and differential scanning calorimetry (DSC). Lower critical solution temperatures (LCST) of the synthesized copolymers were determined. Temperature-sensitive blend microspheres of HPC-g-PAAm and chitosan were prepared by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker in the hydrochloric acid catalyst (HCl) and they were used to achieve controlled release of amoxicillin trihydrate (AMX), an antibiotic drug. The microspheres were characterized by DSC, X-ray diffraction (X-RD), and FTIR spectroscopy. In addition, surfaces of empty and drug-loaded microspheres were examined by scanning electron microscopy (SEM). The effects of variables such as CS/HPC-g-PAAm ratio, drug/polymer ratio, amount of cross-linker, and reaction time of grafting on AMX release were investigated at three different pH environments (1.2, 6.8, 7.4) at 25 °C, 37 °C, and 50 °C. The release results showed that the microspheres had temperature sensitivity and the AMX release was slightly more controlled by especially increasing graft yield (%).

Formulation development and statistical optimization of zingiberol incorporated sodium alginate-methyl cellulose blend microspheres

Formulation development and statistical optimization of zingiberol incorporated sodium alginate-methyl cellulose blend microspheres

Single-dose treatment for cutaneous leishmaniasis with an easily synthesized chalcone entrapped in polymeric microparticles.

Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2',4',6'-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis - infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.

Kinetic study and in vitro drug release studies of nitrendipine loaded arylamide grafted chitosan blend microspheres

Hypertension continues to be a significant public health concern because of its associated morbidity, mortality, and economic impact on society. By the year 2025, 1.56 billion individuals will have hypertension. Nitrendipine, an antihypertensive drug, is used in this present study. Hydrophilic matrices are capable of controlling the release of the drug over an extended period. Microsphere based sustained drug delivery systems will provide a suitable alternative to reduce the side effects and increase the dissolution rate of the drug compared to oral drug delivery. We prepared drug encapsulated microspheres of acrylamide grafted chitosan (hydrophilic polymers) by the free radical mechanism. This mechanism involves the use of an initiator, potassium persulfate. Microspheres were synthesized from the grafted copolymers using water in oil emulsion technique with a cross-linking agent. Differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy were used to characterize the sample. The microspheres at stomach media showed low drug release characteristics, while at the intestinal organ, the drug release prolonged for 14 h. From the drug release kinetic models, Higuchi and zero-order were found to be the best model for the three ratios based on the correlation coefficient. The diffusion component is less than 0.5, which indicates quasi-fickian diffusion. From the kinetic study results, we concluded that the formed acrylamide grafted chitosan microspheres deliver the drug through the diffusion mechanism. Nitrendipine loaded microspheres prepared using water in oil emulsion technique showed favorable sustained drug release behavior.

Mucoadhesive improvement of alginate microspheres as potential gastroretentive delivery carrier by blending with Bletilla striata polysaccharide

As polysaccharide from Bletilla striata (BSP) was anticipated with mucoadhesive improvement in sodium alginate (SA) microspheres, BSP was mixed with SA to construct a composite microsphere to retain in the gastrointestinal tract for a long time. The morphological properties, particle size and thermodynamic properties of the microspheres in combination with comprehensive evaluations in the swelling properties, mucin adsorption, ex vivo and in vivo gastric retention were determined to characterize the mucoadhesion of SA-BSP blend microspheres. Results showed that the prepared microspheres were discrete and spherical. The addition of BSP increased flexibility and reduced rigidity of SA microsphere. Furthermore, the swelling property, mucin adsorption ability and the retention rate on the gastric mucosa of SA matrix were increased after blending with BSP. Mucoadhesion tests showed the SA-BSP microspheres stayed much longer in rats' stomach than the SA microsphere did. Above all, the SA-BSP microspheres with the enhanced mucoadhesion suggested being a potential drug carrier in developing the gastroretentive drug delivery system.

Taro-corms mucilage-alginate microspheres for the sustained release of pregabalin: In vitro &in vivo evaluation

Taro corms mucilage (TCM)-alginate microspheres had been prepared using TCM and alginate as blend and coated form in various ratios through inotropic gelation approach. The prepared microspheres have been of sphere-formed having coarse surface with average particle size within the range 498 μm ± 0.17 to 715 μm ± 0.34. The drug entrapment efficiency was 74.33 ± 0.04% to 89.63 ± 0.01% and swelling of microspheres followed the pattern (blended >coated >plain). FTIR research showed that there had been no interactions among pregabalin and polymers used; these microspheres were further characterized by DSC and XRD. The in vitro drug release followed sustained release (Korsmeyer-Peppas model) pattern (R2 = 0.9552–0.9906) and value of n > 1 showed that drug released by means of anomalous (non-Fickian) diffusion. The in vivo research established that there were highly significant difference with p < 0.001 within the pharmacokinetic parameters (Cmax, t½, AUC0-∞, Ke), while pregabalin microspheres in comparison to pure drug. Therefore, it is concluded that blended microspheres has greater bioavailability for pregabalin with sustained release effect. This evolved that TCM has been proved to be emerging potential pharmaceutical excipient for sustained release drug delivery systems.

Fabrication of Gelatin/Karaya gum blend microspheres for the controlled release of Distigmine bromide

This paper reports the fabrication of gelatin/karaya gum microspheres by emulsion crosslinking method for controlled release of distigmine bromide. The microspheres were crosslinked with the help of glutaraldehyde and used for controlled oral delivery of distigmine bromide. The obtained microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Drug release kinetics of the microspheres is investigated in simulated intestinal fluid pH 7.4 at 37oC. Results illustrated that microspheres was influenced by the pH of test mediums, which might be suitable for intestinal drug delivery. The drug release kinetics was analyzed by evaluating the release data using different kinetic models. Keywords: Karaya Gum, Gelatin, microspheres, drug delivery.

Controlled Release Behaviors of Tribenuron Methyl Herbicide and Potassium Nitrate Fertilizer from Natural Polymer Blended Poly(Vinyl Alcohol) Hydrogel Microspheres

Polyvinyl Alcohol (PVA) hydrogel microspheres for controlled release of fertilizer (KNO3) and Tribenuron Methyl Herbicide (TBM) were prepared by blending the naturally occurring Alginate (AL) and Pectin (PE). The cross-linking in PVA hydrogel microspheres was carried out by varying the amount of glutaraldehyde from 0.5-1.0 wt%. To control the loading and release properties of PVA hydrogel microspheres, a small amount of NaCl (0.2 wt%) was also added in formulation of microspheres. The blending of PE and AL in PVA hydrogel microspheres was confirmed with FT-IR spectra and by increased thermal stability PVA hydrogel as determined by Differential Scanning Calorimetry (DSC) and Thermogravimetric (TGA) analysis. The PVA hydrogel microspheres were characterized for degree of swelling and for loading and cumulative release of fertilizer (KNO3) and herbicide (TBM), which were carried out in solutions of different pH and at different temperatures. The Scanning Electron Micrographs (SEM) of PVA hydrogel microspheres were recorded before and after the release of loaded agrochemicals and used to confirm the shape and homogeneous blending of PE/AL in PVA hydrogels. The enhanced brittle morphology form SEM images of PVA hydrogel microspheres after the release of loaded agrochemicals has suggested the controlled release of agrochemicals through a mechanism of degradation of polymer chains. Thus natural polymer blended PVA hydrogel microspheres are found to be a potential candidate for the formulation of controlled release systems for the application of agrochemicals in soils and to overcome the environmental problem, which usually encountered on applications of fertilizers and herbicides in agricultural fields by conventional methods.

Synthesis of polyorganophosphazenes and fabrication of their blend microspheres and micro/nanofibers as drug delivery systems

Four amino acid-based polyorganophosphazenes were synthesized and characterized by 1H NMR, 31P NMR and GPC. Individually, the synthesized polyorganophosphazenes were blended with two commonly used biocompatible polymers, poly (methyl methacrylate) (PMMA) and polylactic-co-glycolic acid (PLGA) to fabricate anticancer drug loaded micro/nanofibers and microspheres. The nature of side groups, blend composition and drug contents were particularly found significant to adjust the surface morphology, hydrolytic degradation and drug loading/release behavior of microspheres. Moreover, higher in vitro drug release rate was observed in acidic medium. Collectively, our findings suggest that amino acid-based polyorganophosphazenes blend’ systems may provide a therapeutic strategy for cancers.

Preparation and evaluation of chitosan-tripolyphosphate nanoparticles suspension as an antibacterial agent

Interpenetrating polymer network of cross-linked blend microspheres for controlled release of Acebutolol HClP. Ramakrishna, B. Mallikarjuna, A. Chandra Babu, P. Sudhakar, K. Chowdoji Rao, M.C.S. Subha

Evaluation of Multifunction Bioactivities of Extracted Chitosan and their UV/Ozone Derivatives

Interpenetrating polymer network of cross-linked blend microspheres for controlled release of Acebutolol HClP. Ramakrishna, B. Mallikarjuna, A. Chandra Babu, P. Sudhakar, K. Chowdoji Rao, M.C.S. Subha

Synthesis of polyphosphazene and preparation of microspheres from polyphosphazene blends with PMMA for drug combination therapy

Drug combination therapy is an emerging technology to treat the diseases which are still annoyance to human being. Combination of two or more drugs can deal with diseases in a better way. Various different techniques have been introduced which can deliver combination of drugs in a safe and more controlled manner. In our research, we prepared polyphosphazene-based blend microspheres which can deliver two different drugs in a much sustained manner for long time. “Acetamidophenol,” commonly used drug, was attached to the polyphosphazene main chain to produce drug–polymer conjugates, and these were then blended with PMMA in different ratios to fabricate the microspheres of variable and controlled size. Another anticancer drug “camptothecin” was loaded in these microspheres to fabricate dual-drug-loaded microsphere. Furthermore, in vitro drug release behaviors of fabricated microspheres were also demonstrated.