Improved Drug Release Research Articles

Carboxymethyl Chitosan/Starch/CuO Nanocomposite Hydrogels for Controlled Release of Amoxicillin

The drug delivery approach was developed through effective preparation of nanocomposite hydrogels in situ while CuO nanoparticles were being formed within swollen CMCS/starch hydrogels. Nanocomposite hydrogel have obtained significant attention in recent years as one of the most promising nanoparticulate drug delivery systems owing to their unique potentials by combining the characteristics of a hydrogel system with a nanoparticle. The obtained nanocomposite hydrogels were used as a potential candidate for controlled release of amoxicillin drug. Different experimental techniques, including XRD, EDX, and SEM were applied to study and compare the prepared hydrogels. XRD and EDX analyses confirmed the formation of nanoparticles in the hydrogel matrix, while SEM micrographs showed that CuO nanoparticles ranged from 13.89 to 47.78 nm within the same matrix, respectively. According to the results, increased number of nanoparticles resulted from increased ion concentration. At pH 1.2 and pH 7.4, the nanocomposite hydrogels were investigated in terms of the swelling behavior; in comparison with neat CMCS/starch hydrogel, they showed a pH-sensitive swelling ratio. Prolonged and more controlled drug releases were observed for CuO nanoparticle containing CMCS/starch hydrogel, which increased with the rise in CuO nanoparticle content. The objective of this study is to prepare a new, improved drug release using pH-sensitive polymers of carboxymethyl chitosan/starch with the weight ratios of 3:1, 1:1, and 1:3 containing copper oxide nanoparticles. Through in situ formation of nanoparticles in the CMCS/starch hydrogel matrix, the successful preparation of new CMCS/starch nanocomposite hydrogels was achieved. It was attempted to show how the concentration of the nanoparticles in the nanocomposite hydrogel influences the swelling behavior in buffer solutions and drug release behavior.

Use of calcium carbonate as an excipient for release of poorly water soluble drugs: The case of carbamazepine.

Carbamazepine (CBZ) is a poorly water soluble drug owing to the Biopharmaceutic Classification System (BCS) class II. It is characterized by a variable bioavailability and by the presence of different polymorphs. In this paper the effects of CaCO3 on the physicochemical properties of CBZ and its solubility and release were evaluated. CaCO3 is a naturally non-toxic biomineral and was chosen because it is a safe, cheap and eco-friendly excipient able to dissolve in an acidic environment. Composites with different CBZ loadings were prepared by ball milling and antisolvent method. The composites were characterized by X-ray powder diffraction, differential scanning calorimetry analysis and attenuated total reflectance FT-IR which revealed that both the presence of CaCO3 and the preparation procedure affect the polymorphic form crystallinity and intermolecular interactions among the drug molecules. Scanning electron microscopy showed that small drug crystals with different crystalline forms were deposited on the surface of the CaCO3 particles. Solubility and dissolution tests showed an increase in the apparent solubility of CBZ and improved drug release. These results demonstrated that CaCO3 affected the drug release properties likely due to its pH-sensitive characteristics.

Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer. In present study, nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2 (MMP-2) dual-responsive, tumor targeting, and size-variability were designed for enhancing the antitumor efficacy and achieving “on-demand” drug release markedly. Based on the thermal sensitivity of gelatin, we designed a size-variable gelatin nanoparticle (GNP) to encapsulate indocyanine green (ICG) and doxorubicin (DOX). Under an 808 nm laser irradiation, GNP-DOX/ICG responded photothermally and swelled in size from 71.58 ± 4.28 to 160.80 ± 9.51 nm, which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics. Additionally, GNP-DOX/ICG showed a size reduction of the particles to 33.24 ± 4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor. In the subsequently performed in vitro experiments, it was confirmed that GNP-DOX/ICG could provide a therapeutic effect that was enhanced and synergistic. Consequently, GNP-DOX/ICG could efficiently suppress the growth of 4T1 tumor in vivo. In conclusion, this study may provide a promising strategy in the rational design of drug delivery nanosystems based on gelatin for chemo-photothermal therapy to achieve synergistically enhanced therapeutic efficacy against breast cancer.

Controlled loading of albumin-drug conjugates ex vivo for enhanced drug delivery and antitumor efficacy

To harness the intrinsic transport properties of albumin yet improve the therapeutic index of current in situ albumin-binding prodrugs, we developed albumin-drug conjugates with a controlled loading that achieved better antitumor efficacy. Here, model drug monomethyl auristatin E (MMAE) was conjugated ex vivo to Cys34 of albumin via a cathepsin B-sensitive dipeptide linker to ensure that all drug would be bound specifically to albumin. The resulting albumin-drug conjugate with a drug to albumin ratio (DAR) of 1 (ALDC1) retained the native secondary structure of albumin compared to conjugate with a higher DAR of 3 (ALDC3). ALDC1 exhibited improved drug release and cytotoxicity compared to ALDC3 in vitro. Slower plasma clearance and increased drug exposure over time of ALDC1 were observed compared to ALDC3 and MMAE prodrug. In single dose studies with MIA PaCa2 xenografts, cohorts treated with ALDC1 had the highest amount of MMAE drug in tumor tissues compared to other treatment arms. After multiple dosing, ALDC1 significantly delayed the tumor growth compared to control treatment arms MMAE, MMAE-linker conjugate and ALDC3. When dosed with the maximum tolerated dose of ALDC1, there was complete eradication of 83.33% of the tumors in the treatment group. Ex vivo conjugated ALDC1 also significantly inhibited tumor growth in an immunocompetent syngeneic mouse model that better recapitulates the phenotype and clinical features of human pancreatic cancers. In summary, site-specific loading of drug to albumin at 1:1 ratio allowed the conjugate to better maintain the native structure of albumin and its intrinsic properties. By conjugating the drug to albumin prior to administration minimized premature cleavage and instability of the drug in plasma and enabled higher drug accumulation in tumors compared to in situ albumin-binding prodrugs. This strategy to control drug loading ex vivo ensures complete drug binding to the albumin carrier and achieves excellent antitumor efficacy, and it has the potential to greatly improve the outcomes of anticancer therapy.

Synthesis of ‘dual-key-and-lock’ drug carriers for imaging and improved drug release

In this work, a ‘dual-key-and-lock’ drug carrier was designed to respond to the tumor microenvironment (TME). A core–shell Fe-MOF@ZIF-8 was synthesized, with ZIF-8 as the shell (the first lock) to encapsulate catalase (CAT), and the Fe metal–organic framework (MOF) as the core (the second lock) to encapsulate the anticancer drug doxorubicin (DOX). Fe-MOF@ZIF-8 takes advantage of the TME—which includes a high concentration of H2O2, a weakly acidic environment and hypoxia—to achieve efficient cancer therapy. With the pH response, ZIF-8 and Fe-MOF are degraded in turn to release CAT and DOX, just like ‘pH stimulation’, as a key to open the two locks in turn. The released CAT reacts with the rich H2O2 in the tumor to produce O2 to regulate hypoxia, thereby improving the anticancer efficiency of the released DOX. The different cytotoxicity to L-02 cells and HeLa cells of Fe-MOF@ZIF-8 shows Fe-MOF@ZIF-8 is only harmful to cancer cells and is not harmful to normal cells. The reason is that the Fe2+/Fe3+ in Fe-MOF interact with the rich H2O2 in cancer cells to generate hydroxyl radicals (ċOH), which is proved by the color of the solution of 3,3′,5,5′-tetramethylbenzidine turning blue. After loading of the drug and CAT, Fe-MOF@ZIF-8 can release CAT, DOX and ċOH in response to the TME, thus killing more HeLa cells. Therefore, synthesis of ‘dual-key-and-lock’ drug carriers responsive to the TME is a promising strategy for cancer treatment.

Tailoring hybrid organic-inorganic film forming topical gel: A tuneable approach for Tramadol HCl delivery

ABSTRACT Drug release properties for transdermal route can be better modified as per requirement which is mostly dependent upon the carrier system. In case of organic film-forming systems, the physical properties may not be achieved for successful delivery of drug through transdermal route. A novel organic-inorganic hybrid film-forming gel may fulfil these expectations to many extend. The present study focuses on the development of the organic-inorganic hybrid film-forming gel. A smooth, transparent, clear film-forming gel of tramadol was prepared for application on the intact skin with better comfort and modified drug release rate properties. The key properties of the adhesive films produced from the hybrid gels were investigated and the results showed that the incorporation of appropriate PVA: TEOS: Glycerine: HCl in the ratio of 46:12.5:25.5:6 respectively. Resultant hybrid film-forming gel has modified the physical properties and improved drug release properties. Furthermore, the investigations of skin irritation suggested no irritation to skin after topical application. This study has provided an alternative to the presently available organic gel and films for transdermal delivery of drugs with better patient compliance and modified physical and chemical stability.

Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery.

In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33±0.91°C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r>0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer.

Budesonide-Cyclodextrin in Hydrogel System: Impact of Quaternary Surfactant on in vitro-in vivo Assessment of Mucosal Drug Delivery

Budesonide, a glucocorticosteroid is generally used to treat chronic inflammation and asthma. Hepatic first-pass metabolism and poor solubility are the major causes of its limited oral bioavailability. Present work was undertaken for the preparation of hydrogel film formulation with cyclodextrin complexation of budesonide containing quaternary surfactant for possible enhancement of mucosal permeation. FTIR study confirmed drug-polymer hydrogen bonding. Almost complete amorphization of the drug was pronounced by SEM, DSC and XRD studies. The film containing benzalkonium and hydroxypropyl beta-cyclodextrin exhibited in vitro dissolution and mucosal permeation to the highest extent of 87.2 and 95.8 % respectively in contrast to the others. Film formed hydrogel in aqueous mucin and enhanced the mucosal tissue residence time due to the mucoadhesive nature of the polymer. Acute inflammation in the rabbit eye was controlled within 3 h by applying the film in the cul-de-sac. The presence of cyclodextrin and quaternary surfactant brought about significantly improved drug release and mucosal permeation compared to their absence in the HPMC film. Hydrogel formed in aqueous mucin enhanced the mucosal residence time and controlled acute inflammation in the rabbit eye within 3 h after topical application.

Development and in vitro Evaluation of Gastro-protective Aceclofenac-loaded Self-emulsifying Drug Delivery System.

AimChronic use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) is commonly associated with gastric irritation and gastric ulceration. Therefore, the aim of study was to develop a novel oral drug delivery system with minimum gastric effects and improved dissolution rate for aceclofenac (ACF), a model BCS class-II drug.MethodsSelf-emulsifying drug delivery systems (SEDDS) were formulated to increase the solubility and ultimately the oral bioavailability of ACF. Oleic acid was used as an oil phase, Tween 80 (T80) and Kolliphor EL (KEL) were used as surfactants, whereas, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) were employed as co-surfactants. Optimized formulations (F1, F2, F3 and F4) were analyzed for droplet size, poly dispersity index (PDI), cell viability studies, in vitro dissolution in both simulated gastric fluid and simulated intestinal fluid, ex vivo permeation studies and thermodynamic stability.ResultsThe optimized formulations showed mean droplet sizes in the range of 111.3 ± 3.2 nm and 470.9 ± 12.52 nm, PDI from 244.6 nm to 389.4 ± 6.51 and zeta-potential from −33 ± 4.86 mV to −38.5 ± 5.15 mV. Cell viability studies support the safety profile of all formulations for oral administration. The in vitro dissolution studies and ex vivo permeation analysis revealed significantly improved drug release ranging from 95.68 ± 0.02% to 98.15 ± 0.71% when compared with control. The thermodynamic stability studies confirmed that all formulations remain active and stable for a longer period.ConclusionIn conclusion, development of oral SEDDS might be a promising tool to improve the dissolution of BCS class-II drugs along with significantly reduced exposure to gastric mucosa.

Studies on formulation development and evaluation of tolnaftate-loaded glycerosomes

ABSTRACT Purpose The aim was to formulate and evaluate glycerosomes as novel carrier for dermal (trans) drug delivery systems (tDDDS). Methods Tolnaftate Loaded Glycerosomes were prepared by thin film hydration technique. The thin-film was hydrated using aqueous solution of glycerol (30 %v/v) against liposomes as control and were characterized. Results Glycerosome formulations were sphere-shaped with a mean diameter of 165.5 nm and narrow size distribution (P.I: 0.744). Zeta potential was –22.8mv indicating good stability. Tolnaftate loading capacity was found to be between 17.5±0.56 % and 91.32±0.57%. In-vitro permeation experiments showed an improved skin deposition and permeation of tolnaftate (5mg) when 30% glycerol, DSPC (100mg), cholesterol (25mg) content were used. Ex-vivo skin penetration studies showed an improved drug release than conventional liposomes and drug suspension. Skin irritancy studies on guinea pig showed no signs of toxicity. Conclusion Glycerosomes must be an ideal novel transdermal drug delivery system for the effective delivery of tolnaftate.

Formulation optimization and in vitro characterization of rifampicin and ceftriaxone dual drug loaded niosomes with high energy probe sonication technique

The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.

MnFe2O4 nanoparticles/cellulose acetate composite nanofiber for controllable release of naproxen

Nanofibers have been demonstrated to be highly effective for drug delivery applications. Although magnetic nanoparticles (MNPs) have been potentially added to nanofibers for improved drug release stimulation, the effect has been limited. In this study, a magnetic nanofiber membrane composed of cellulose acetate (CA), collagen (COL), and MnFe2O4 MNPs was prepared by electrospinning. Naproxen (NAP) drug was deposited on the nanofibers, and the drug release mechanism and effect of the MNPs on the stimulated NAP release were investigated. The electrical conductivity of the dope solution strongly affected the nanofiber characteristics. Moreover, the MTT cytotoxicity assay proved that CA-COL, CA-COL-NAP, and CA-COL-NAP-MNP nanofibers had low toxicity, as the cell viability was >80%. The NAP release mechanism was determined using zero-order, first-order, Higuchi, and Korsmeyer-Peppas kinetics models. According to the dissolution results, for all nanofibers, the NAP release followed the Korsmeyer-Peppas kinetics model, and the transport mechanism was Fickian diffusion. A high MNP concentration and neutral pH condition were conducive to NAP release.

Synthesis and Characterization of Orotic Acid Loaded Chitosan Inclusion Complex

The current study aims to improve drug release properties of orotic acid loaded with chitosan inclusion complex (OA/CS). The OA/CS inclusion complex was synthesized using the freeze-drying technique. The characterization of inclusion OA/CS was carried out using fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), zeta sizer, and transmission electron microscopy (TEM). Furthermore, the size of OA/CS ranged between 58 nm and 200 nm, and the zeta potential was 30 mV. Thus, this study indicates that OA/CS has a promising future to develop a carrier for drug delivery systems further.

The effects of Fe3+ and Co2+ substitution in Ca10-x-yFexCoy(PO4)6(OH)2 hydroxyapatite nanoparticles: Magnetic, antibacterial, and improved drug release behavior

The mineral constituent of the bone contains non-stoichiometric hydroxyapatite with various substitutional ions. Iron (Fe) and cobalt (Co) are fundamental cofactors, which influence cell respiration and mitosis, respectively. In this study, undoped, Fe3+-, Co2+-, and dually-doped HA nanoparticles (NPs) were synthesized by the hydrothermal method. The Fe+CoCa+Fe+Co molar ratio was varied between 0.02 and 0.2. Samples were analyzed using X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), vibrating sample magnetometry (VSM), Fourier-transformed infrared spectroscopy (FT-IR), inductively coupled plasma optical emission spectroscopy (ICP-OES), and biological assessment. XRD results confirmed the formation of the hexagonal HA crystal structure. The crystallite size was reduced from 34.6 nm to 4.4 nm. Also, the c-axis dimension and the degree of crystallinity were reduced in all the doped samples. The FESEM results showed a change of morphology from rod-like in the undoped nHA into a sphere-like morphology in the doped-samples. With the addition of ferromagnetic dopant, the magnetic behavior of samples altered from diamagnetic to paramagnetic-like and ferromagnetic behavior. Bioactivity assessment indicated the formation of the HA particle on the surface of all synthesized materials. The antibacterial test demonstrated antibacterial activity against gram-negative (−) E. coli. Moreover, the antibiotic-impregnated samples had a synergistic effect on both gram (−), E. coli, as well as gram (+), S. aureus, bacteria. The MTT evaluation revealed the enhanced cell viability of osteoblast-like cells in the dually-doped NPs. Based on this survey, we can strongly emphasize the potential for bone bioactivity and antibacterial feature of these newly developed samples.

Electrodeposited Assembly of Additive-Free Silk Fibroin Coating from Pre-Assembled Nanospheres for Drug Delivery.

Electrophoretically deposited (EPD) polymer-based coatings have been extensively reported as reservoirs in medical devices for delivery of therapeutic agents, but control over drug release remains a challenge. Here, a simple but uncommon assembly strategy for EPD polymer coatings was proposed to improve drug release without introducing any additives except the EPD matrix polymer precursor. The added value of the proposed strategy was demonstrated by developing a novel EPD silk fibroin (SF) coating assembled from pre-assembled SF nanospheres for an application model, that is, preventing infections around percutaneous orthopedic implants via local delivery of antibiotics. The EPD mechanism of this nanosphere coating involved oxidation of water near the substrate to neutralize SF nanospheres, resulting in irreversible deposition. The deposition process and mass could be easily controlled using the applied EPD parameters. In comparison with the EPD SF coating assembled in a conventional way (directly obtained from SF molecule solutions), this novel coating had a similar adhesion strength but exhibited a more hydrophobic nanotopography to induce better fibroblastic response. Moreover, the use of nanospheres as building blocks enabled 1.38 and 21 times enhancement on the antibiotic release amount and time (of 95% maximum dug release), respectively, while retaining drug effectiveness and showing undetectable cytotoxicity. This unexpected release kinetics was found attributable to the electrostatic and hydrophobic interactions between the drug and nanospheres and a negligible initial dissolution effect on the nanosphere coating. These results illustrate the promising potential of the pre-assembled strategy on EPD polymer coatings for superior control over drug delivery.

Polymeric Nanosuspension Loaded Oral Thin Films of Flurbiprofen: Design, Development and In Vitro Evaluation

In the present investigation, effort has been made to stabilize optimized nanosuspension of flurbiprofen through oral thin film formulation. To overcome the issue of stability of nanosuspension and poor bioavailability of flurbiprofen, nanosuspension loaded oral thin films were developed by solvent casting method. Oral thin films can be prepared by simple and scalable method easily. Nanosuspension loaded oral thin films were evaluated for thickness, % moisture absorption and loss, surface pH, weight variation, folding endurance, drug content, disintegration time, in vitro drug release and stability. The resultant oral thin films depicted that the particles size range was retained even after their stability study for three months. The dissolution rate of all flurbiprofen oral thin films were significantly increased compared with its marketed oral formulation. Thus it can be concluded that, oral thin films have potential for stabilization of nanosuspension with improved drug release.

Studies on Span based Soy-bigels with HPMC

Organogels owing to their lipophilic nature and better stability over other gel preparations may have a wide range of application but leaching of oily phase restricts their application. Use of hydrogel is limited by its stability problems and syneresis at atmospheric condition. Attempts to overcome such drawbacks can be overcome by combining both lipophilic organogel and hydrophilic hdydrogel phases in a single formulation, bigel. The present study deals with the development and evaluation of soy-bigel by mixing organogel of soybean oil (prepared with Span 40 or Span 60) and hydrogel of HPMCK4M or HPMCK15M in a definite ratio. Four batches of soy-bigels were prepared by mixing organogel with 18%w/v Span and 3% HPMC hydrogel. Formulations were examined for compatibility by FTIR spectroscopy, characterized for physical appearance, pH, rheological behavior, in vitro drug release pattern and thermal stability study. FTIR study confirmed compatibility between paracetamol and components of bigel. Soy-bigels were found to possess satisfactory organoleptic properties and applicability parameters and demonstrated pseudoplastic flow behavior. Better drug release was observed in soy-bigel prepared with Span 40 and HPMCK4M (OHP2) which followed Kormeyer-Peppas model with non-Fickian diffusion. Diffusion-controlled drug release gradually decreased in gels of matrix type developed with Span 60 and either grade of HPMC (OHS1 and OHS2). Soy-bigels prepared from Span 40 and either grades of HPMC demonstrated thermal stability on exposure to 5 freeze-thaw cycles. Thus, soy-bigels prepared from Span 40 and HPMCK4M exhibited satisfactory rheological property and improved drug release and can ideally be selected as a topical base for drug delivery.

Adjudin-loaded redox-sensitive paclitaxel-prodrug micelles for overcoming multidrug resistance with efficient targeted Colon cancer therapy

Multidrug resistance (MDR) is the primary cause for the failure of chemotherapy in the treatment of colon cancer. Recent research has indicated that the combination of a chemotherapeutic agent and a mitochondrial inhibitor might represent a promising strategy to help overcome MDR. However, for this approach to be clinically effective, it is important that the two drugs can be actively and simultaneously delivered into tumor cells at an optimal ratio and completely released drug within cells. To address these challenges, we designed and prepared a folate receptor-targeted and redox-responsive drug delivery system (FA- ss -P/A) that was able to co-deliver paclitaxel (PTX) and adjudin (ADD) to reverse colon cancer MDR. The PTX prodrug was obtained by conjugating PTX to dextrin via a disulfide-linkage. Then, folic acid (FA) was modified on the PTX prodrug. Finally, ADD, a mitochondrial inhibitor, was encapsulated in the PTX prodrug-formed micelles. A series of in vitro and in vivo experiments subsequently demonstrated that FA- ss -P/A can effectively reverse MDR by increasing cell uptake, inhibiting PTX efflux, and improving drug release.

Utilization of green formulation technique and efficacy estimation on cell line studies for dual anticancer drug therapy with niosomes.

The aim of the present study was to prepare niosome formulations for the simultaneous encapsulation, dual drug therapy, of two anticancer drugs by the ecological probe sonication method. Poloxamer and sorbitan monostearate were used as surface active agents in niosomes, and the water soluble doxorubicin and poorly-water soluble paclitaxel were used as anticancer drugs. Thorough physicochemical analysis were performed for the niosomes, and their cytotoxicity and activity were evaluated on MCF-7 and PC3-MM2 cancer cell lines. Prepared niosomes were small in size with sizes ranging from 137 nm to 893 nm, and entrapment efficiencies were high, ranging from 91.24% to 99.99%. During the four weeks stability testing, the particle size remained stable. The niosomal formulations showed in vitro sustained drug release profiles for doxorubicin and clearly increased the dissolution rate of poorly water soluble paclitaxel. The incorporation of both the drugs into niosomes improved cell penetration and antiproliferative activity of the drugs PC3-MM2 cell lines. As a conclusion, doxorubicin and paclitaxel loaded niosome formulations resulted in relatively stable, small sized niosomes with improved drug release profiles, low toxicity, better cell penetration and antiproliferative activity. The niosomes showed synergistic effect due to the presence of both drugs, which can overcome multidrug resistance.

Solvent-free Hot Melt Extrusion Technique in Improving Mesalamine Release for Better Management of Inflammatory Bowel Disease

Abstract: Background: Poor oral bioavailability of mesalamine (Mes) is due to extensive metabolism in the intestinal epithelial cells in addition to the liver. Purpose: Improved mesalamine release by Hot-Melt Extrusion (HME) technique could be utilized for better management of Inflammatory Bowel Disease (IBD). Methods: Mes and hydrophilic polymers like Eudragit- EPO, KollidonVA-64 and PEG 6000 were hot-melt extruded using a co-rotating twin-screw laboratory extruder. Results: The minor shifting with significantly reduced intensity and disappearance of peak in the Differential Scanning Calorimetry (DSC) thermogram could be attributed to some solid–solid interaction and not necessarily any incompatibility. Fourier-Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) confirmed the transformation of individual drug crystal into accumulations of small crystallites due to partial or almost complete amorphization. Continuous manufacturing of stable amorphous solid dispersion by solvent-free drug loading Hot-melt extrusion technique has been found feasible in improving drug release compared to mesalamine alone in simulated gastric fluid (f1= 0.3 to 11.1 and f2 = 26 to 49). Conclusion: Melt dispersion samples have exhibited significantly improved mesalamine release and could be utilized for better management of Inflammatory Bowel Disease (IBD). Key words: Hot-melt extrusion, Solvent-free drug loading, Mesalamine, Feret diameter, Improving Release.