Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.

Synthesis, characterization, pharmacological and computational evaluation of hyaluronic acid modified chebulinic acid encapsulated chitosan nanocomposite for cancer therapy.

The purpose of this study was to produce hyaluronic acid customized nanoparticles with chitosan for the delivery of chebulinic acid (CLA) to enhance its anticancer potential against breast cancer. A significant portion of CLA was encapsulated (89.72 ± 4.38 %) and loaded (43.15 ± 5.61 %) within hybrid nanoparticles. The colloidal hybrid nanoparticles demonstrated a polydispersity index (PDI) of about 0.379 ± 0.112, with zeta capacitance of 32.69 ± 5.12 (mV), and an average size of 115 ± 8 (nm). It was found that CLA-CT-HA-NPs had stronger anticancer effects on MCF-7 cells (IC50 = 8.18 ± 3.02 µM) than pure CLA (IC50 = 17.15 ± 5.11 µM). The initial cytotoxicity findings were supported by additional investigations based on comet assay and flow cytometry analysis. Tumor remission and survival were evaluated in five separate groups of mice. When juxtaposed with pure CLA (3.17 ± 0.419 %), CLA-CT-HA-NPs improved survival rates and reduced tumor burden by 3.76 ± 0.811(%). Furthermore, in-silico molecular docking investigations revealed that various biodegradable polymers had several levels of compatibility with CLA. The outcomes of this study might potentially served as an effective strategy for delivering drugs in the context of breast cancer therapy.

Mucoadhesive, Fluconazole-Loaded Nanogels Complexed with Sulfhydryl-ß-cyclodextrin for Oral Thrush Treatment.

The objective of this study was to generate fluconazole-loaded mucoadhesive nanogels to address the problem of hydrophobicity of fluconazole (FL). An inclusion complex was formulated with sulfhydryl-ß-CD (SH-ß-CD) followed by nanogels formation by a Schiff base reaction of carbopol 940 (CA-940) and gelatin (GE). For characterization, PXRD, FT-IR analysis, drug content, and phase solubility studies were performed. Similarly, nanogels were assessed for particle size, zeta potential, organoleptic, and spreadability studies. Moreover, drug contents, rheological, in vitro drug permeation, release kinetics, toxicity, and stability studies of nanogels were performed. Furthermore, mucoadhesive characteristics over the buccal mucosal membrane of the goat were evaluated. The nanogels formulated with a higher amount of CA-940 and subsequently loaded with the inclusion complexes of FL showed promising results. PXRD and FT-IR analysis confirmed the physical complexes by displaying a reduction in the intensity of peaks of FL. The average particle size of nanogels was in the range of 257 to 361 nm. The highest drug content of 88% was encapsulated within the FL-SH-ß-CD complex. All formulations at 0.5-1% concentration displayed no toxicity to the Caco-2 cell lines. Nanogels loaded with FL-SH-ß-CD complexes showed 18-fold improved mucoadhesion on the buccal mucous membrane of the goat when compared to simple nanogels. The in vitro permeation study exhibited significantly enhanced permeation and first-order concentration-dependent drug release was observed. On the bases of these findings, we can conclude that a mucoadhesive nanogel-based drug delivery system can be an ideal therapy for candidiasis.

Self-emulsifying drug delivery systems: A versatile approach to enhance the oral delivery of BCS class III drug via hydrophobic ion pairing.

Biopharmaceutical classification systems (BCS) class III drugs belongs to a group of drugs with high solubility in gastrointestinal (GI) fluids and low membrane permeability result in significantly low bioavailability. Self-emulsifying drug delivery systems (SEDDS) considered a suitable candidate to enhance the bioavailability of poorly soluble drugs by improving their membrane permeability, however, incorporating hydrophilic drugs in to these carriers remained a great challenge. The aim of this study was to develop hydrophobic ion pairs (HIPs) of a model BCS class-III drug tobramycin (TOB) in order to incorporate into SEDDS and improve its bioavailability. HIPs of TOB were formulated using anionic surfactants sodium docusate (DOC) and sodium dodecanoate (DOD). The efficiency of HIPs was estimated by measuring the concentration of formed complexes in water, zeta potential determination and log P value evaluation. Solubility studies of HIPs of TOB with DOC were accomplished to screen the suitable excipients for SEDDS development. Consequently, HIPs of TOB with DOC were loaded into SEDDS and assessed the log DSEDDS/release medium and dissociation of these complexes at different intestinal pH over time. Moreover, cytotoxic potential of HIPs of TOB and HIPs loaded SEDDS formulations was evaluated. HIPs of TOB with DOC exhibited the maximum precipitation efficiency at a stoichiometric ratio of 1:5. Log P of HIPs of TOB improved up to 1500-fold compared to free TOB. Zeta potential of TOB was shifted from positive to negative during hydrophobic ion pairing (HIP). HIPs of TOB with DOC was loaded at a concentration of 1% (w/v) into SEDDS formulations. Log DSEDDS/release medium of loaded complexes in to oily droplets was above 2 and dissociated up to 20% at various pH within 4 h. Finding of this study suggested that improvement of the lipophilic character of BCS class-III drugs followed by incorporation into oily droplets can be deliberated as a promising tool to enhance the permeation across biological membranes.

Enhanced Intestinal Permeability of Cefixime by Self-Emulsifying Drug Delivery System: In-Vitro and Ex-Vivo Characterization.

BACKGROUND: Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to significantly low bioavailability. AIM: This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS. METHODS: Suitable excipients were selected based on drug solubility, percent transmittance, and emulsification efficiency. Pseudo-ternary phase diagram was fabricated for the identification of effective self-emulsification region. The best probably optimized formulations were further assessed for encumbered drug contents, emulsification time, cloud point measurement, robustness to dilution, mean droplet size, zeta potential, polydispersity index (PDI), and thermodynamic and chemical stability. Moreover, in vitro drug release studies and ex vivo permeation studies were carried out and apparent drug permeability Papp of different formulations was compared with the marketed brands of CFX. RESULTS: Amongst the four tested SEDDS formulations, F-2 formulation exhibited the highest drug loading of 96.32%, emulsification time of 40.37 ± 3 s, mean droplet size of 19.01 ± 1.12 nm, and demonstrated improved long-term thermodynamic and chemical stability when stored at 4 °C. Release studies revealed a drug release of 97.32 ± 4.82% within 60 min in simulated gastric fluid. Similarly, 97.12 ± 5.02% release of CFX was observed in simulated intestinal fluid within 120 min; however, 85.13 ± 3.23% release of CFX was observed from the marketed product. Ex vivo permeation studies displayed a 2.7-fold increase apparent permeability compared to the marketed product in 5 h. CONCLUSION: Owing to the significantly improved drug solubility, in vitro release and better antibacterial activity, it can be assumed that CFX-loaded SEDDS might lead to an increased bioavailability and antibacterial activity, possibly leading to improved therapeutic effectiveness.

Corrigendum to "Life-Threatening Severe Thrombocytopenia and Mild Autoimmune Hemolytic Anemia Associated with Brucellosis".

[This corrects the article DOI: 10.1155/2023/6608279.].

Life-Threatening Severe Thrombocytopenia and Mild Autoimmune Hemolytic Anemia Associated with Brucellosis.

Methods: We report the case of a 73-year-old Saudi female who presented with severe thrombocytopenia and mild autoimmune hemolytic anemia associated with brucellosis. The coexistence of published cases of two hematological disorders with brucellosis is rare. Results: Despite the initial treatment with eltrombopag and intravenous immunoglobulin (IVIG), our patient's platelets count remained low and significantly improved after initiation of brucellosis treatment in the form of rifampicin and doxycycline. Discussion. We conclude by reviewing the case that in many parts of Saudi Arabia, brucellosis remains a prevalent infection. Hence, it should be considered as a possible diagnosis in febrile individuals with no localizing indications and the presence of severe thrombocytopenia in acute febrile illness. Although it is a rare association, it could be related to brucellosis. Conclusion: This is our region's first published case of severe thrombocytopenia and mild autoimmune hemolytic anemia associated with brucellosis. It contributes to the literature on the successful use of rifampicin and doxycycline to treat hematological disorders associated with brucellosis.

Nano-Formulation Based Intravesical Drug Delivery Systems: An Overview of Versatile Approaches to Improve Urinary Bladder Diseases.

Intravesical drug delivery is a direct drug delivery approach for the treatment of various bladder diseases. The human urinary bladder has distinctive anatomy, making it an effective barrier against any toxic agent seeking entry into the bloodstream. This screening function of the bladder derives from the structure of the urothelium, which acts as a semi-permeable barrier. However, various diseases related to the urinary bladder, such as hyperactive bladder syndrome, interstitial cystitis, cancer, urinary obstructions, or urinary tract infections, can alter the bladder's natural function. Consequently, the intravesical route of drug delivery can effectively treat such diseases as it offers site-specific drug action with minimum side effects. Intravesical drug delivery is the direct instillation of medicinal drugs into the urinary bladder via a urethral catheter. However, there are some limitations to this method of drug delivery, including the risk of washout of the therapeutic agents with frequent urination. Moreover, due to the limited permeability of the urinary bladder walls, the therapeutic agents are diluted before the process of permeation, and consequently, their efficiency is compromised. Therefore, various types of nanomaterial-based delivery systems are being employed in intravesical drug delivery to enhance the drug penetration and retention at the targeted site. This review article covers the various nanomaterials used for intravesical drug delivery and future aspects of these nanomaterials for intravesical drug delivery.

Fenugreek seed mucilage grafted poly methacrylate pH-responsive hydrogel: A promising tool to enhance the oral bioavailability of methotrexate.

This study aimed to develop the Fenugreek seed mucilage-based pH-responsive hydrogel system in order to improve the oral bioavailability of methotrexate (MTX). Fenugreek seed mucilage (FSM) was extracted from Trigonella foenum-graecum seeds. F1-F9 formulations of pH-responsive hydrogels were prepared using various FSM ratios, methacrylic acid (MAA), and methylene bis acrylamide (MBA) via free radical polymerization technique. Swelling behavior and in vitro drug release studies of prepared hydrogels were evaluated. Toxicity studies of prepared hydrogels were performed on normal cells and on Wistar rats (n = 6). Moreover, in vivo pharmacokinetics parameters were studied on albino rabbits. Hydrogels formation was confirmed by FTIR analysis, thermal analysis and SEM studies. The maximum swelling of hydrogel was found to be 384.7% at pH 7.4. MTX-loaded hydrogel showed the controlled release of MTX up to 24 h following Super Case II transport. Prepared hydrogels exhibited no toxicity in normal cells as well as in experimental subjects. MTX loaded hydrogels exhibited less inhibition compared to free MTX on Hela cells. In Vivo studies revealed 7.5-fold improved oral bioavailability of MTX with higher Cmax (928 ng/mL). These results indicate that the pH-responsive hydrogel system based on FSM is a promising tool for the controlled delivery of MTX.

Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In-Silico Modelling and In-Vivo Toxicity Evaluation.

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (ß-CD) and sulfobutyl ether7 ß-CD (SBE7 ß-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 ß-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5-348.4 nm, with polydispersity index (PDI) ranging from 0.302-0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75-88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

Diabetic retinopathy service delivery and integration into the health system in Pakistan-Findings from a multicentre qualitative study.

This paper is based on qualitative research carried out in a diabetic retinopathy (DR) programme in three districts of Pakistan. It analyses the organisation and delivery of DR services and the extent to which the interventions resulted in a fully functioning integrated approach to DR care and treatment. Between January and April 2019, we conducted 14 focus group discussions and 37 in-depth interviews with 144 purposively selected participants: patients, lady health workers (LHWs) and health professionals. Findings suggest that integration of services was helpful in the prevention and management of DR. Through the efforts of LHWs and general practitioners, diabetic patients in the community became aware of the eye health issues related to uncontrolled diabetes. However, a number of systemic pressure points in the continuum of care seem to have limited the impact of the integration. Some components of the intervention, such as a patient tracking system and reinforced interdepartmental links, show great promise and need to be sustained. The results of this study point to the need for action to ensure inclusion of DR on the list of local health departments' priority conditions, greater provision of closer-to-community services, such as mobile clinics. Future interventions will need to consider the complexity of adding diabetic retinopathy to an already heavy workload for the LHWs.

Oral bioavailability studies of niosomal formulations of Cyclosporine A in albino rabbits.

Cyclosporine A (CsA) is an immunosuppressant agent. Two niosomal formulations of CsA, FTS and FSB were formulated. Both formulations were studied in terms of size, polydispersity index (PDI), morphology and entrapment efficacy etc. Niosomal formulations FTS and FSB and plain aqueous dispersion were given to three assemblies of Albino rabbits (n=8 per group). CsA levels in plasma were determined at appropriate time intervals and pharmacokinetic parameters were evaluated. The percentage entrapment efficiencies of FTS and FSB were found to be 77.29 and 89.31% for respectively. Transmission electron microscopy results indicated spherical nature of niosomes. In vivo studies demonstrated that the value of Cmax for the FSB formulation was 1968.419 ng/ml and it was 1498.951 ng/ml and 1073.87 ng/ml for FTS and aqueous dispersion of CsA (control) respectively. It was found that both niosomal formulation FTS & FSB presented significantly high (p<0.05) Cmax, AUC0-t, MRT 0-inf and half-life (t1/2) as associated to plain drug dispersion. However niosomal formulation FSB exhibited better in-vivo performance as compared to FTS. It was established that CsA can be successfully entrapped in niosomes. So niosomes are promising vehicle for CsA oral delivery.

Understanding the role of lady health workers in improving access to eye health services in rural Pakistan - findings from a qualitative study.

BACKGROUND: In 1994, the Lady Health Workers (LHWs) Programme was established in Pakistan to increase access to essential primary care services and support health systems at the household and community levels. In Khyber Pakhtunkhwa (KPK) province in northern Pakistan, eye care is among the many unmet needs that LHWs were trained to address, including screening and referral of people with eye conditions to health facilities. However, despite an increase in referrals by LHWs, compliance with referrals in KPK has been very low. We explored the role of LHWs in patient referral and the barriers to patient compliance with referrals. METHODS: Qualitative methodology was adopted. Between April and June 2019, we conducted eight focus group discussions and nine in-depth interviews with 73 participants including patients, LHWs and their supervisors, district managers and other stakeholders. Data were analysed thematically using NVivo software version 12. RESULTS: LHWs have a broad understanding of basic health care and are responsible for a wide range of activities at the community level. LHWs felt that the training in primary eye care had equipped them with the skills to identify and refer eye patients. However, they reported that access to care was hampered when referred patients reached hospitals, where disorganised services and poor quality of care discouraged uptake of referrals. LHWs felt that this had a negative impact on their credibility and on the trust and respect they received from the community, which, coupled with low eye health awareness, influenced patients' decisions about whether to comply with a referral. There was a lack of trust in the health care services provided by public sector hospitals. Poverty, deep-rooted gender inequities and transportation were the other reported main drivers of non-adherence to referrals. CONCLUSIONS: Results from this study have shown that the training of LHWs in eye care was well received. However, training alone is not enough and does not result in improved access for patients to specialist services if other parts of the health system are not strengthened. Pathways for referrals should be agreed and explicitly communicated to both the health care providers and the patients.

Enhanced Oral Bioavailability of Epalrestat SBE7-ß-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation.

BACKGROUND: Epalrestat (EPL) is a carboxylic acid derivative with poor aqueous solubility and its pharmacokinetic features are not fully defined. PURPOSE: Current research aimed to fabricate inclusion complexation of EPL with SBE7 ß-CD (IC) and EPL/SBE7 ß-CD CS NPs (NP). METHODS: EPL was complexed with SBE7 ß-CD using the co-precipitation method, and the prepared complex was fabricated into nanoparticles using the ionic gelation method. The prepared formulations were characterized for particle size analysis, surface morphology, and in vitro dissolution study. The % inhibition of EPL against α-glucosidase enzyme was also conducted to check the drug's antidiabetic activity. Finally, an in vivo pharmacokinetic investigation was carried out to determine the concentration of EPL in rabbit plasma of the prepared formulation. In vivo pharmacokinetic studies were conducted by giving a single dose of pure EPL, IC, and NP. RESULTS: The size of NP was found to be 241.5 nm with PDI 0.363 and zeta potential of +31.8 mV. The surface of the prepared NP was non-porous, smooth and spherical when compared with pure EPL, SBE7 ß-CD and IC. The cumulative drug release (%) from IC and NP was 73% and 88%, respectively, as compared to pure drug (25%). The % inhibition results for in vitro α-glucosidase was reported to be 74.1% and the predicted binding energy for in silico molecular docking was calculated to be -6.6 kcal/mol. The calculated Cmax values for EPL, IC and NP were 4.75±3.64, 66.91±7.58 and 84.27±6.91 µg/mL, respectively. The elimination half-life of EPL was 4 h and reduced to 2 h for IC and NP. The AUC0-α for EPL, IC and NP were 191.5±164.63, 1054.23±161.77 and 1072.5±159.54 µg/mL*h, respectively. CONCLUSION: Taking these parameters into consideration it can be concluded that IC and NP have prospective applications for greatly improved delivery and regulatedt release of poorly water soluble drugs, potentially leading to increase therapeutic efficacy and fewer side effects.

Zeta potential changing nanoemulsions based on a simple zwitterion.

HYPOTHESIS: Simple zwitterions used as auxiliary agents might have the potential to change the zeta potential of oil-in-water (o/w) nanoemulsions on the mucosa. EXPERIMENTS: The zwitterion phosphorylated tyramine (p-Tyr) was synthesized by phosphorylation of Boc-tyramine (Boc-Tyr) using phosphoryl chloride (POCl3). It was incorporated with 2% (m/v) in a self-emulsifying lipophilic phase comprising Captex 35, Cremophor EL, Capmul MCM and glycerol 85 at a ratio of 30:30:30:10 v/v. Phosphate release and resulting change in zeta potential were evaluated by incubating p-Tyr containing nanoemulsion with isolated intestinal alkaline phosphatase (AP). Mucus permeating behavior was evaluated across mucus obtained from porcine small intestinal mucosa. Subsequently, cellular uptake studies were accomplished on Caco-2 cells. FINDINGS: The p-Tyr loaded nanoemulsion exhibited a mean droplet size of 43 ± 1.7 nm and zeta potential of -8.40 mV. Phosphate moieties were rapidly cleaved from p-Tyr loaded nanoemulsions after incubation with isolated AP resulting in a shift in zeta potential from -8.40 mV to +1.2 mV. p-Tyr loaded nanoemulsion revealed a significantly (p ≤ 0.001) improved mucus permeation compared to the same nanoemulsion having been pre-treated with AP. Cellular uptake of the zeta potential changing oily droplets was 2.4-fold improved. Phosphorylated zwitterions seem to be an alternative to cationic surfactants and considered as promising auxiliary agents for zeta potential changing nanoemulsions.

S-Protected thiolated nanostructured lipid carriers exhibiting improved mucoadhesive properties.

The purpose of the present study was to design nanostructured lipid carriers (NLCs) exhibiting improved mucoadhesive properties. First, an S-protected thiolated fatty acid conjugate was synthesized by amide bond formation between a primary amino group of l-cystine and palmitic acid N-hydroxysuccinimide. NLCs were prepared by nano-template engineering technique using Span 60, polysorbate 80, sucrose stearate and PEG 400 as surfactant mixture, stearic acid as solid lipid and miglyol as liquid lipid. NLCs were loaded with the model drug bergapten and decorated with the S-protected thiolated fatty acid conjugate. NLCs were characterized regarding particle size, poly-dispersity index (PDI), zeta potential, drug entrapment efficiency (EE), drug loading capacity (LC), drug release and mucoadhesive properties. Furthermore, cytotoxicity studies were performed on MDA-MB-231 cells via resazurin assay. S-Protected thiolated NLCs displayed a mean size of 115 nm, PDI of 0.3, zeta potential of -30 mV, 80% drug EE and 5% drug LC. Drug-loaded S-protected thiolated NLCs exhibited a sustained drug release and strongly enhanced mucoadhesive properties. Surface decoration with cystine substructures raised the cytotoxic potential of NLCs to a minor extent. Due to the immobilization of cystine substructures on the surface of NLCs, their mucoadhesive properties can be strongly improved.

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro.

The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5'-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.

Image-guided catheter drainage in loculated pleural space collections, effectiveness, and complications.

INTRODUCTION: Image-guided drainage is an established technique with a multitude of applications. The indications, techniques, and management of image-guided catheter drainage, however, continue to evolve. Image-guided drainage alone is sometimes sufficient for the treatment of a collection, but it can also act as an adjunct or temporizing measure before definitive surgical treatment. Drainage of a symptomatic collection is performed to drain pus from the cavity, working in conjunction with antibiotics. Infected collections accumulate antibiotics to a limited extent, which generally precludes effective treatment with antibiotics alone unless the collection is very small (1-3 cm). There are many indications for image-guided drainage in the chest, including pleural disease, lung parenchymal, pericardial, and mediastinal collections. Pleural collections represent a common clinical problem, for which image-guided drainage is recommended to reduce complications encountered as a result of blind drainage. AIM AND OBJECTIVE: To evaluate the efficacy and complications of ambulatory catheter drainage system for infective and loculated pleural collection. MATERIALS AND METHODS: The study was conducted in the department of radiodiagnosis and imaging, Sheri Kashmir Institute of Medical Sciences Srinagar 2016 to 2018. It was prospective in nature. All the patients were referred from in patient department as cases of clinically symptomatic pleural collections with image-based evidence of loculations or septations. All 30 patients referred for drainage were imaged using suitable imaging technique (USG or CT) to quantise and document presence of septations and loculations in pleural collections. Mean attenuation of pleural fluid, presence of internal echo's and associated pleural thickening (>2mm) was noted. RESULTS: The overall success rate in our study was 77%, with recurrence in 10 % of patients and failure rate of 13 %. The outcome as per etiology was success rate of 100% in parapneumonic effusion, 70 % in TB, 50 % in malignancy and 100% in pleural collection after recent surgical intervention. The common procedure related complications noted in our study were hemothorax (3%), post procedural pain (23 %), pneumothorax (3%). CONCLUSION: Image guided percutaneous drainage of loculated pleural space collections is an effective and safe procedure.

About the impact of superassociation of hydrophobic ion pairs on membrane permeability.

AIM: The study was aimed to investigate the impact of superassociation of hydrophobic ion pairs (HIPs) on membrane permeability. METHODS: Toluidine blue O (TBO) as a cationic model compound was complexed with anionic counter ions having different physiochemical properties namely dodecanoate (DD), oleate (OL), deoxycholate (DC), docusate (DO) and dodecyl sulfate (DS). TBO HIPs were characterized regarding log P, zeta potential and stability over 8 h at pH 7.4. Association and dissociation constants (Ka and Kd) were calculated by applying quasi-equilibrium equation to the double reciprocal plots of log P versus counter ion concentrations. Permeation studies of free TBO, superassociated TBO HIPs and HIPs applied as entirely dissociated form were carried out across human colorectal adenocarcinoma-derived cell line (Caco-2) and freshly excised rat intestinal mucosa. RESULTS: TBO HIPs of increasing lipophilicity ranging from log P 0.59 to 2.35 were obtained as a result of ion pairing with anionic counter ions. Zeta potential of TBO shifted from positive to negative due to ion pairing. HIPs with DO and DS showed highest stability at pH 7.4. Association constant (Ka) values for TBO HIPs were found in the following rank order; DS > DO > OL > DC > DD. Due to superassociation of HIPs, permeation of TBO was efficiently improved up to 3.1-fold across Caco-2 cells and up to 2.5-fold across rat intestinal mucosa. CONCLUSION: Superassociated HIPs showed generally a significantly higher membrane permeability than free TBO and entirely dissociated HIPs.

Development, characterization and evaluation of anti-fungal activity of miconazole based nanogel prepared from biodegradable polymer.

Topical candidiasis is a known skin fungal infection which is usually treated by conventional dosage forms such as cream, gel, emulgel which are having numerous adverse effects on skin. To overcome such disadvantages, different novel drug delivery systems have been considered. Polymer based nano-particulate systems have shown good skin penetration after topical application. Therefore, in the present study the main focus was on the pathology, pathogenesis, and consequently topical treatment of candidiasis. Nanogel containing miconazole have been prepared from the natural polymers i.e. gelatin and chitosan. The nanogel of miconazole (100 mg) nitrate was formulated by modified emulsification-diffusion technique and characterized for different parameters. From all the seven nanogel formulations named as F1 to F7, F1 (Gelatin and Chitosan in the percentage of 82.85 and 17.15 respectively) have been selected as model formulations. The reason behind that was as per ICH stability guideline, the formulations F1 was found optimum and stable. Miconazole nanogel formulations F1 also showed the maximum release i.e. 78 % approximately. XRD showed the formulated nanogel was in crystalline shape. In summary, the miconazole nanogel drug delivery systems have two main advantages i.e. they are topical preparation as well as nano sized. It can be postulated that nanogel may be a best approach to treat the fungal skin diseases.