Sustained Drug Delivery System Research Articles

Preparation and Evaluation of Itraconazole Nanoparticle Lipid Carrier Gel for Dermatophytosis

Fungal infection is one of the common dermatological diseases. Drug delivery systems for topical use have shown significant advantages in targeting the drug to the action site in the body and also reduces the systemic side effects. Itraconazole was chosen as a model drug with low aqueous solubility. In the present study an attempt was made to prepare itraconazole loaded nanostructured lipid carrier (NLC). Different formulations were prepared by hot homogenization technique using solid lipid and liquid lipid (Compritol 888 & Caprol PGE 860) and surfactants (Poloxamer 188, tween 80). All the Formulations were characterized for drug content, entrapment efficiency, particle size, poly dispersity index, zeta potential &in vitro drug release and FTIR was done to study any interaction between excipients. The best formulation shows better drug release and entrapment efficiency 83.2%. the best formulation F3 showed better in-vitro drug release 55.46% at the end of 8th hour. The F3 was made into gel using Carbopol as a gelling agent. SEM study revealed that the NLC gel shows the particle size was found to be 500 nm in size smooth surfaces. NLC gel shows Drug release of NLC gel followed non- Fickian diffusion. NLC gel were stable at 40 ± 2ֹ°C and 75 ± 5% RH. Thus, the prepared NLC gel proved to be a potential candidate as a topical nanoparticulate sustained drug delivery system for itraconazole (BCS class II drug). keywords: Itraconazole, Nanoparticle Lipid Carrier, Lipids.

Scope and Application of Hot Melt Extrusion in the Development of Controlled and Sustained Release Drug Delivery Systems.

Controlled-release drug delivery systems (CRDDS) are more beneficial than conventional immediate release (IRDDS) for reduced intake, prolonged duration of action, lesser adverse effects, higher bioavailability, etc. The preparation of CRDDS is more complex than IRDDS. The hot melt extrusion (HME) technique is used for developing amorphous solid dispersion of poorly water soluble drugs to improve their dissolution rate and oral bioavailability. HME can be employed to develop CRDDS. Sustained release delivery systems (SRDDS), usually given orally, can also be developed using HME. This technique has the advantages of using no organic solvent, converting crystalline drugs to amorphous, improving bioavailability, etc. However, the heat sensitivity of drugs, miscibility between drug-polymer, and the availability of a few polymers are some of the challenges HME faces in developing CRDDS and SRDDS. The selection of a suitable polymer and the optimization of the process with the help of the QbD principle are two important aspects of the successful application of HME. In this review, strategies to prepare SRDDS and CRDDS using HME are discussed with its applications in research.

Gastro-retentive drug delivery system of hypertension drug: Formulation and evaluation study

Introduction: Hypertension, a major global health concern, necessitates effective management through sustained drug delivery systems. Gastro-retentive drug delivery systems (GRDDS) offer a strategic advantage by prolonging the residence time of drugs in the stomach, thus enhancing therapeutic efficacy and patient adherence. This study aims to develop and evaluate a GRDDS for antihypertensive drugs to achieve extended gastric retention and controlled release. Methods: A GRDDS was formulated using a combination of hydrophilic and hydrophobic polymers to ensure buoyancy and extended gastric retention. The formulation process involved selecting optimal polymer concentrations and incorporating release-modulating agents. In vitro evaluations included buoyancy studies, swelling behavior analysis, and drug release kinetics under simulated gastric conditions. Additionally, in vivo studies were conducted to assess the system’s gastric retention and pharmacokinetic profile in an animal model. Conclusion: The developed GRDDS demonstrated effective gastric retention and a controlled release profile for the antihypertensive drug. In vitro results confirmed the system’s ability to maintain buoyancy and provide sustained drug release. In vivo studies supported these findings, showing improved drug bioavailability and stable plasma levels. This GRDDS represents a promising advancement in hypertension management, potentially enhancing therapeutic outcomes and patient compliance. Further research and clinical trials are recommended to validate these preclinical results and optimize the system for broader application.

Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing.

Intravaginal rings (IVRs) represent a well-established, woman-controlled and sustained vaginal drug delivery system suitable for a wide range of applications. Here, we sought to investigate the differences in etonogestrel (ENG) and ethinyl estradiol (EE) release from a 3D-printed IVR utilizing continuous liquid interface production (CLIP™) (referred to as CLIPLOW for low drug loading and CLIPHIGH IVRs for high drug loading) and NuvaRing, a commercially available injection molded IVR. We conducted in vitro release studies in simulated vaginal fluid to compare the release of ENG and EE from CLIPLOW IVRs and NuvaRing. CLIPLOW IVRs had a similar hormone dose to NuvaRing and exhibited slightly slower ENG release and greater EE release in vitro compared to NuvaRing. When administered to female sheep, NuvaRing demonstrated greater ENG/EE levels in plasma, vaginal tissue and vaginal fluids compared to CLIPLOW IVR despite similar drug loadings. Leveraging observed hormones levels in sheep from NuvaRing as an effective contraceptive benchmark, we developed a long-acting CLIPHIGH IVR with increased ENG and EE doses that demonstrated systemic and local hormone levels greater than the NuvaRing for 90 days in sheep. No signs of toxicity were noted regarding general health, colposcopy, or histological analysis in sheep after CLIPHIGH IVR administration. Our results provided (1) a comparison of ENG and EE release between a 3D-printed IVR and NuvaRing in vitro and in vivo, (2) a preclinical pharmacokinetic benchmark for vaginally delivered ENG and EE and (3) the generation of a 90-day CLIP IVR that will be utilized in future work to support the development of a long-acting ENG/EE IVR combined with an antiretroviral for the prevention of HIV and unplanned pregnancy.

Quantitative analysis of loxoprofen sodium loaded microspheres comprising pectin and its thiolated conjugates: In-vivo evaluation of their sustained release behavior

Continuous use of oral NSAIDs can damage mucosal membrane, which results in decreased bioavailability and non-compliance with the therapy. But the use of sustained release drug delivery systems might offer a solution. Objective was to synthesize mucoadhesive SR microspheres by using different combinations of pectin (PEC) and its thiolated derivative (T-PEC3100) for improved loxoprofen (LS) permeation. Thiolated pectin (T-PEC) was synthesized by the esterification method using thioglycolic acid. Thiolation was confirmed by thiol group quantification and charring point determination. Further characterization was done by Fourier Transform Infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM). Ex-vivo mucoadhesion study was performed to confirm the improved characteristics. Microspheres (MS) were prepared using different ratios of PEC/T-PEC by solvent evaporation method and their particle size and surface morphology were evaluated. Mucus permeation study was carried out using the trans-well plate method. Sustained release behavior of prepared microspheres was investigated through the edema inhibition method in albino rats. T-PEC3100 was considered the optimum formulation for further evaluation and contained maximum thiol group content. FTIR spectra showed a characteristic peak of –SH and charring point was also changed considerably confirming the successful thiolation of PEC. SEM results showed spherical microspheres in the size range of 2–10 μm. Thiol-rich formulation of MS exhibited more than 80 % release after 12 h and maximum absorbable dose (MAD) was calculated as 400 μg % inhibition of edema in MS treated group was slowly attained initially but the reduction in inflammation was detected even after 24 h as compared to control group. Promising results from In-vivo edema inhibition study suggest the possible use of these thiolated MS in formulating sustained release formulation for arthritis.

A hybrid formulation of porous silicon nanoparticle with carboxymethyl cellulose for enhanced drug loading

Porous silicon nanoparticles (pSiNPs) have received considerable spotlight in drug delivery systems due to their biocompatibility, drug loading capacity, and easy surface modification. Despite these merits, the degradation rate control of pSiNPs in biological environments remains a challenge for sustained-release applications. In this study, we introduce a novel formulation of pSiNPs-based coated with carboxymethyl cellulose (pSiNPs-CMC) for the first time. The drug loading and release behavior of pSiNPs-CMC, featuring representative anticancer drugs such as doxorubicin, gemcitabine, paclitaxel, and SN-38, were extensively characterized. Notably, the CMC coating on pSiNPs resulted in an increase in loading efficiency of over 60% both for hydrophilic and hydrophobic drugs, while ensuring a controlled and tailored drug release profile. Our findings present the potential of the pSiNPs-CMC composite as a robust and versatile platform, overcoming conventional limitations in drug specificity and representing a significant advancement in sustained and personalized drug delivery systems.

In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits.

Siponimod is a promising agent for the inhibition of ocular neovascularization in diabetic retinopathy and age-related macular degeneration. Siponimod's development for ophthalmological application is hindered by the limited information available on the drug's solubility, stability, ocular pharmacokinetics (PK), and toxicity in vivo. In this study, we investigated the aqueous stability of siponimod under stress conditions (up to 60 °C) and its degradation behavior in solution. Additionally, siponimod's ocular PK and toxicity were investigated using intravitreal injection of two different doses (either 1300 or 6500 ng) in an albino rabbit model. Siponimod concentration was quantified in the extracted vitreous, and the PK parameters were calculated. The drug half-life after administration of the low and high doses was 2.8 and 3.9 h, respectively. The data obtained in vivo was used to test the ability of published in silico models to predict siponimod's PK accurately. Two models that correlated siponimod's molecular descriptors with its elimination from the vitreous closely predicted the half-life. Furthermore, 24 h and 7 days after intravitreal injections, the retinas showed no signs of toxicity. This study provides important information necessary for the formulation and development of siponimod for ophthalmologic applications. The short half-life of siponimod necessitates the development of a sustained drug delivery system to maintain therapeutic concentrations over an extended period, while the lack of short-term ocular toxicity observed in the retinas of siponimod-treated rabbits supports possible clinical use.

Lactic acid and hydroxyl terminated polybutadiene assisted synthesis of vegetable oil based polyurethanes for sustained drug delivery systems

The present research aims to develop a series of biodegradable, sustainable and biocompatible, polyurethanes (PU–S1 to PU-S4). The synthesis of these polyurethanes involved a combination of different ratios of an epoxidized polyol (followed by ring opening with ethanol) extracted from soybean oil, along with hydroxyl-terminated polybutadiene (HTPB). The lactic acid was esterified with ethylene glycol to produce a sustainable chain extender which was used to increase the molecular weight of the final polymer. FTIR spectroscopy and scanning electron microscopy (SEM) were used for the characterization of the PU samples. The thermal degradation behavior and wetting ability of the PUs were also determined through contact angle, indicating a gradual decrease in hydrophilicity with increasing HTPB content finally made a little hydrophobic surface in the case of PU-S4 sample (contact angle = 96.46°). The potential of these polyurethanes (PUs) as drug delivery systems was checked using gabapentin as a prototypical drug. It was dispersed into the polymer matrix via the solvent evaporation process. The analysis of drug release adhered to US Pharmacopeial guidelines was determined using 0.06 N HCl as the release medium. Sample PU-S4 showed a higher drug release, reaching 56.0 % after 6 h. Additionally, a regular trend was observed in different PU samples, suggesting an increase in HTPB content with a decrease in drug release.

Tissue engineered multifunctional chitosan-modified polypropylene hernia mesh loaded with bioactive phyto-extracts

Surface modified tissue engineered polypropylene / PP hernia meshes were fabricated by incorporating Bacterial cellulose / BC and chitosan / CS and phytochemical extracts. Under current practice, hernia and other traumatic injuries to the abdominal organs are clinically treated with surgical meshes. Often the foreign body reaction and infections result in relapse in patients which dictates additional reparative surgical procedures and pain. To improve the outcome of clinical restorative procedures new biomaterials with improved characteristics are required. The functionalized meshes were physically and chemically characterized using SEM, mechanical testing, FTIR and XRD. The antimicrobial activity was qualitatively and quantitatively tested using E. coli and S. aureus strains of bacteria. In vitro biocompatibility and wound healing effect of the modified meshes were performed using NIH3T3 fibroblast cell lines. Furthermore, tissue engineering potential of the meshes was evaluated using confocal fluorescent microscopy. In vivo implantation of the meshes was performed in male wistar rats for 21 days. Therefore, PP meshes with sustained drug delivery system augmented with anti-inflammatory and anti-microbial characteristics were developed. The coatings hereby not only increased the tensile strength of meshes but also prevented the modified meshes from causing infection. Current study resulted in CS-BC bioactive PP meshes loaded with phytochemicals which showed anti-inflammatory, antibacterial and wound healing potential. These meshes can be valuable to lessen the post-surgical complications of implanted PP mesh and thus reduce rejection and recurrence.

Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis.

This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.

Design, Synthesis, and Evaluation of Lipoyl Ester Conjugated Star PLGA for Sustained Drug Delivery Systems

Background: Poly(lactic-co-glycolic acid) (PLGA), an FDA-approved copolymer, is widely recognized for its biocompatibility, biodegradability, and versatility in drug delivery systems. Despite its advantages, challenges, such as poor drug loading and burst release, motivate the exploration of innovative modifications. The current research aimed to modify the linear PLGA to lipoyl ester terminated star PLGA polymer to minimize initial burst release by increasing the molecular weight and fabricate risperidone-loaded microspheres. Methods: In this study, we have presented a novel approach involving the synthesis of star PLGA through the direct melt polycondensation of PLGA with pentaerythritol, followed by conjugation with lipoic acid to form lipoyl ester terminated star PLGA. Structural confirmation was done by Fourier Transform Infrared spectroscopy (FT-IR), proton Nuclear Magnetic Resonance (1H-NMR), and Gel Permeation Chromatography (GPC). Microspheres were fabricated from lipoyl ester terminated star PLGA and characterized for their particle size and surface morphology by Scanning Electron Microscopy (SEM) and in vitro drug release by dialysis bag method Results: The results of the study have indicated successful conjugation of lipoic acid to star PLGA forming lipoyl ester terminated star PLGA, as confirmed by FT-IR, 1H-NMR, and GPC analyses. Microspheres developed from the synthesized polymer exhibited particle sizes ranging from 4.64 μm to 11.7 μm and demonstrated sustained drug delivery, with 99.8% release over 45 d, in contrast to the plain drug that achieved complete dissolution within 3 h. Conclusion: The resulting material has demonstrated unique bioresponsive and multifunctional properties, with evidence of successful synthesis provided through comprehensive characterization techniques, and suitability for the fabrication of microspheres for sustained drug delivery systems.

Yeast‐Controlled Double‐Shelled CaCO3/CaF2 Hollow Nanospheres with Hierarchically Porous for Sustained pH‐Sensitive Drug Release

Comprehensive SummaryHierarchically porous materials (HP materials) are believed one of the most hopeful matrix materials because of their distinctive multimodal pore structures and tremendous application potentials in the field of biomedicine. However, green and facile synthesis of hierarchically porous nanomaterials with beneficial water dispersibility and biocompatibility is still a great challenge. Herein, a novel biomimetic strategy is proposed to prepare the cell‐tailored double‐shelled HPCaCO3/CaF2 hollow nanospheres under the mediation of yeast cells. The biomolecules derived from the secretion of yeast cells are used as conditioning and stabilizing agents to control the biosynthesis of the HPCaCO3/CaF2 materials, which exhibit excellent water dispersibility and favorable biocompatibility. The double‐shelled CaCO3/CaF2 nanospheres hold hierarchically porous structure and have abundant pore channel and large specific surface area, showing high drug‐loading and a prolonged drug sustainable release profile by the pore‐by‐pore diffusion pattern of the hierarchical pores. Otherwise, the HPCaCO3 with pH‐sensitivity could controllably release drug doxorubicin hydrochloride (DOX) at the acidic tumor microenvironment. Both in vitro and in vivo results demonstrate that HPCaCO3/CaF2 has the sustainable pH‐sensitive drug release property, showing an enhanced therapeutic effect. Summarily, this study provides a biomimetic strategy to synthesize the hierarchically porous double‐shelled hollow nanomaterials for applying in sustainable drug delivery system.

Zwitterionic functionalization of polysaccharide gum by graft copolymerization to develop 3-D network materials for anticancer drug delivery applications

Herein, functionalization of polysaccharide gum has been carried out to develop network copolymeric materials for use in sustained anticancer drug delivery. Grafting reaction of poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSAH) onto sterculia gum has been done in the presence of crosslinker. Copolymeric materials were characterized by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 13C-nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). SEM, AFM and XRD displayed heterogeneous morphology with a rough surfaces of amorphous copolymeric materials. Peaks at 173.822 ppm (carbonyl carbon) and at 60.653 ppm (methylene carbon attached to a quaternary ammonium group) confirmed the addition of poly(MEDSAH) during the grafting reaction. Mesh size in network hydrogel was found between 14.54 nm to 36.32 nm. Sustained release of doxorubicin was found with non-Fickian diffusion and was best demonstrated by the kinetic model Hixson Crowell. The biocompatibility of material was revealed in a haemolytic index (1.74 ± 0.26%) less than two percent during the copolymer-blood interaction. The material exhibited antioxidant and mucoadhesion properties. Free radical scavenging ability of copolymers was 49.41 ± 0.97% in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay of the antioxidant test. These properties of copolymeric hydrogels demonstrated their suitability for use in sustained drug delivery systems for cancer chemotherapy.

Development of lactic acid based chain extender and soybean oil-derived polyurethanes for ecofriendly sustained drug delivery systems

In the present study, a range of sustainable, biocompatible and biodegradable polyurethanes (PU-1 to PU-4) were synthesized using different combinations of biobased polyol (obtained through the epoxidation of soybean oil, followed by ring opening with ethanol) and polyethylene glycol (PEG) and isophorone diisocyanate. The sustainable chain extender used in this study was synthesized by the esterification of lactic acid with ethylene glycol (EG). The synthesized PU samples were characterized through scanning electron microscopy (SEM), Fourier transformed infrared (FTIR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopy. Wetting ability and thermal degradation analysis (TGA) of the samples were also studied. Subsequently, these PUs were examined as potential drug delivery systems using Gabapentin as a model drug, which was loaded in the polymer matrix using the solvent evaporation method. The drug release studies were carried out in 0.06 N HCl as a release medium according to the method outlined in the United States Pharmacopeia. The maximum drug release was observed for sample PU-P1, which was found to be 53.0 % after 6 h. Moreover, a comparison of different PU samples revealed a trend wherein the values of drug release were decreased with an increase in the PEG content.

Functionalization of Arabinoxylan in Chitosan Based Blends by Periodate Oxidation for Drug Release Study

AbstractThis article presents the isolation of arabinoxylan (AX) from Plantago ovata seed husk and its oxidation using periodate to create oxidized‐AX (OAX) with distinct functionalities. Utilizing the solution casting method, biocompatible blends of arabinoxylan/chitosan (AX/CS) are prepared at various weight ratios, and their properties are assessed. Fourier transform infrared spectroscopy (FT‐IR), x‐ray diffraction (XRD), and thermogravimetric analysis (TGA) are employed to gauge compatibility and thermal traits of AX and OAX with CS. Solubility tests reveal partial and limited solubility of AX and OAX in distilled water, respectively. OAX displays favorable compressibility and flow rate through Carr's index, Hausner's ratio, and angle of repose analyses. FT‐IR data confirm intermolecular hydrogen bonding between CS′s −NH2− group and OAX′s carbonyl group, with XRD showing low crystallinity. Diclofenac sodium (DC) is loaded as a model drug into AX/CS and OAX/CS blends for release studies in pH 6.8 phosphate buffer. Results exhibit OAX/CS blends with sustained drug release, surpassing AX/CS blends. Among ratios tested, the OAX/CS (1 : 2) blend emerges as a superior excipient, demonstrating enhanced in‐vitro release potential, highlighting oxidized blends′ promise in sustained drug delivery systems.

Polydopamine-Modified Titanium Dioxide Nanotube Arrays Doped with Calcium as a Sustained Drug Delivery System.

Titanium nanotube (TNT) arrays manufactured via electrochemical anodization have been widely used as local drug carriers due to their excellent biocompatibility and customizable nanotubular structures. However, the uncontrollable and abrupt drug release at the early stage decreases the drug release duration, leading to excessive drug concentration at the implantation site. In this study, a continuous drug delivery system based on TNTs was created. Initially, a basic ultrasound-assisted approach was utilized to deposit a polydopamine (PDA) coating onto TNTs to obtain PDA-modified TNTs. Next, TNTs-PDA were submerged in a calcium chloride solution to include Ca2+ through Ca2+ coordination between the PDA layer's catechol groups. Sodium alendronate (NaAL) was used as a model drug and loaded onto TNTs-PDA-Ca2+ by immersing them in an NaAL solution. In the final step, NaAL was covalently attached to TNTs-PDA-Ca2+ through coordination bonds with Ca2+. The samples underwent characterization through the use of various techniques, including field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction patterning, X-ray photoelectron spectroscopy, and inductively coupled plasma emission spectrometry. The results indicated that the bioactivity of TNTs improved, and there was an enhancement in drug loading capacity and release performance due to modification with PDA and Ca2+. Furthermore, acidic conditions can cause significant drug release due to the cleavage of coordination bonds between the drug and Ca2+ ions. Thus, the aforementioned drug delivery system represents a potentially promising approach for achieving sustained and controllable drug release.

RSM optimized chitosan based composite hydrogel for sustained drug delivery applications

Hybrid hydrogels with good biocompatibility have practical applications in the field of drug delivery. However, it remains challenging to formulate the hybrid hydrogels for sustained drug release by regulating their pore size and degradation rates. Herein, a hybrid chitosan-alginate hydrogel (superabsorbent) was synthesized using maleic acid as a cross-linker and acrylamide as a grafting agent. The composite hydrogel exhibited a good swelling percentage of 1246% (at pH 10), analysed using response surface methodology (RSM). The hybrid hydrogel system was hemocompatible as well as biocompatible and utilized for drug delivery applications. Pantoprazole sodium was taken as a model drug and it was loaded in the superabsorbent using the swelling diffusion method. The composite hydrogel showed excellent encapsulation efficiency for pantoprazole sodium (99.74%). The intermolecular interactions between hydrogel and drug were examined using different analytical techniques including XRD (X-Ray Diffraction), FTIR (Fourier transform infrared), SEM (Scanning electron microscope), thermal analysis and EDX (Energy dispersive X-ray) mapping. The swelling percentage of the drug loaded hydrogel under simulated gastrointestinal conditions was recorded as 917.80% (at stomach pH 1.2) and 756.95% (at intestinal pH 7.4) where protonation/deprotonation of the drug in the hydrogel matrix played an important role. In vitro drug release from the drug-loaded hydrogel was sustained up to 10 days and correlated with its swelling tendency, displaying higher release profiles at pH 1.2 (99.69%) than at pH 7.4 (72.16%). The pore volume of hydrogel was tuned varying the cross-linker amount during synthesis. BET (Brunauer-Emmett-Teller) results revealed that the pore volume of the hydrogel varied between 0.01775–0.01327 cm3/g for the cross-linker amount between 0.18–0.26 g, respectively. The impact of various factors including amount of cross-linker, pore volume, and drug loading percentage on drug release at pH 1.2 and 7.4 was studied statistically as well as experimentally and these factors significantly controlled the drug release percentage. The drug release from the hydrogel followed the Makoid-Banakar model with Fickian diffusion mechanism. The synthesized composite chitosan-alginate hydrogel could be a promising candidate for its utilization as a sustained drug delivery system.

Anti-cancer activity of capsaicin and its analogs in gynecological cancers.

Capsaicin is the hot and pungent ingredient of chili peppers. It is a potent pain-relieving agent and is often present in over-the-counter analgesic lotions and creams. Several convergent studies reveal that capsaicin displays growth-suppressive activity in human cancers in vitro and in vivo. Apart from its growth-suppressive activity (as a single agent), capsaicin has been found to sensitize human cancer cells to the pro-apoptotic effects of chemotherapy and radiation. The first part of this book chapter discusses the anti-cancer activity of capsaicin in gynecological cancers in cell culture experiments and mouse models. Out of all gynecological cancers, the anti-cancer activity of capsaicin (and its analogs) has only been investigated in cervical cancers and ovarian cancers. The clinical development of capsaicin as a viable anti-cancer drug has remained challenging due to its poor bioavailability and aqueous solubility properties. In addition, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, irritation in the gut, nausea diarrhea and vomiting. Two strategies have been investigated to overcome these drawbacks of capsaicin. The first is to encapsulate capsaicin in sustained release drug delivery systems. The second strategy is to design non-pungent capsaicin analogs which will retain the anti-tumor activity of capsaicin. The second part of this chapter provides an overview of the anti-neoplastic (and chemosensitization activity) of capsaicin analogs and capsaicin-based sustained release formulations in cervical and ovarian cancers. The design of selective non-pungent capsaicin analogs and capsaicin-based polymeric drug delivery systems may foster the hope of novel strategies for the treatment and management of gynecological cancers.

Intestinal retentive systems - recent advances and emerging approaches.

Intestinal retentive devices (IRDs) are devices designed to anchor within the lumen of the intestines for long-term residence in the gastrointestinal tract. IRDs can enable impactful medical device technologies including sustained oral drug delivery systems, indwelling sensors, or real-time diagnostics. The design and testing of IRDs present a myriad of challenges, including precise deployment of the device at desired intestinal locations, secure anchoring within the gastrointestinal tract to allow for natural function, and safe removal of the IRD at user-defined times. Advancing the state-of-the-art of IRD is an interdisciplinary effort that requires innovations such as new materials, novel anchoring mechanisms, and medical device design with consistent input from clinical practitioners and end-users. This perspective briefly reviews the current state-of-the-art for IRDs and charts a path forward to inform the design of future concepts. Specifically, this article will highlight materials, retention mechanisms, and test beds to measure the efficacy of IRDs and their mechanisms. Finally, potential synergies between IRD and other medical device technologies are presented to identify future opportunities.

FORMULATION, DEVELOPMENT, AND EVALUATION OF OCUSERTS FOR QUINOLONE ANTIBIOTICS

Ophthalmic films are the best sustained-release ocular drug delivery system. The present study targets developing such ocular films of antibacterial with corticosteroid and evaluating its potential. Conventional ocular dosage forms have low bioavailability with low therapeutic response. The solvent cast method employed in ophthalmic films has triggered the minds of researchers to design sustained drug delivery systems overcoming pre-corneal constraints. The compatibility of antibacterial with Loteprednol Etabonate added polymers, excipients were evaluated through preformulation studies. Different combinations of ocular inserts with antibacterial drug and corticosteroid, excipients were formulated and evaluated. Formula CLE 80 (Ciprofloxacin Hydrochloride with Loteprednol Etabonate) fulfilled the needs of all organoleptic parameters like appearance, texture, surface pH, drug content, and in-vitro studies. The results predicted CLE 80 ophthalmic film would be a promising controlled-release formulation for better patient compliance