Why do patients with DR-TB do not complete their treatment? Findings of a qualitative study from Pakistan.

BACKGROUND: One of the major reasons for unsuccessful treatment outcomes among patients with drug-resistant tuberculosis (DR-TB) is the high rate of loss to follow-up (LTFU). However, in Pakistan, no qualitative study has been conducted to explore the perceptions of LTFU patients with regard to DR-TB treatment, the problems they face and the reasons for LTFU in detail. METHODS: This was a qualitative study that involved semistructured, indepth, face-to-face interviews of 39 LTFU patients with DR-TB. All interviews were carried out in Pakistan's national language 'Urdu' using an interview guide in two phases: the first phase was from December 2020 to February 2021 among patients with extensively drug-resistant tuberculosis and the second phase from July 2021 to September 2021 among patients with multidrug-resistant tuberculosis. RESULTS: The inductive thematic analysis of audio-recorded interviews generated the following four key themes, which were the major reasons reported by the participants of the current study to have led to LTFU: (1) patient-related factors, such as lack of awareness about the total duration of DR-TB treatment, fatigue from previous multiple failed episodes, lack of belief in treatment efficacy and perception of DR-TB as a non-curable disease; (2) medication-related factors, such as use of injectables, high pill burden, longer duration and adverse events; (3) socioeconomic factors, such as gender discrimination, poor socioeconomic conditions, non-supportive family members, social isolation and unemployment; and (4) service provider-related factors, such as distant treatment centres, non-availability of a qualified person, lack of adequate counselling and poor attitude of healthcare professionals. CONCLUSION: In the current study, patients' perceptions about DR-TB treatment, socioeconomic condition, medication and service provider-related factors emerged as barriers to the successful completion of DR-TB treatment. Increasing patients' awareness about the duration of DR-TB treatment, interacting sessions with successfully treated patients, availability of rapid drug susceptibility testing facilities at treatment centres, decentralising treatment and using the recently recommended all-oral regimen may further decrease the rate of LTFU.

Highly Responsive Chitosan-Co-Poly (MAA) Nanomatrices through Cross-Linking Polymerization for Solubility Improvement.

In this study, we report the highly responsive chitosan-based chemically cross-linked nanomatrices, a nano-version of hydrogels developed through modified polymerization reaction for solubility improvement of poorly soluble drug simvastatin. The developed nanomatrices were characterized for solubilization efficiency, swelling studies, sol-gel analysis, in vitro drug release studies, DSC, FTIR, XRD, SEM, particle size analysis, and stability studies. An in vivo acute toxicity study was conducted on female Winstor rats, the result of which endorsed the safety and biocompatibility of the system. A porous and fluffy structure was observed under SEM analysis, which supports the great swelling tendency of the system that further governs the in vitro drug release. Zeta sizer analyzed the particle size in the range of 227.8 ± 17.8 nm. Nano sizing and grafting of hydrophilic excipients to the nanomatrices system explains this shift of trend towards the enhancement of solubilization efficiency, and, furthermore, the XRD results confirmed the amorphous nature of the system. FTIR and DSC analysis confirmed the successful grafting and stability to the system. The developed nanomatrices enhanced the release characteristics and solubility of simvastatin significantly and could be an effective technique for solubility and bioavailability enhancement of other BCS class-II drugs. Due to enhanced solubility, efficient method of preparation, excellent physico-chemical features, and rapid and high dissolution and bio-compatibility, the developed nanomatrices may be a promising approach for oral delivery of hydrophobic drugs.

Synthesis and Evaluation of Polyethylene Glycol-4000-Co-Poly (AMPS) Based Hydrogel Membranes for Controlled Release of Mupirocin for Efficient Wound Healing.

BACKGROUND: Chronic wound healing is a major challenge for the health care system around the globe. The current study was conducted to develop and characterize chemically cross-linked polyethylene glycol-co-poly (AMPS) hydrogel membranes to enhance the wound healing efficiency of antibiotic mupirocin (MP). METHODS: Free radical polymerization technique was used to develop hydrogel membranes. In an aqueous medium, polymer PEG-4000 was cross-linked with the monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS) in the presence of initiators ammonium peroxide sulfate (APS) and sodium hydrogen sulfite (SHS). N, N-Methylene-bis-acrylamide (MBA) was used as a cross-linker in preparing hydrogel membranes. Developed membranes were spherical, transparent, and had elasticity. FTIR, TGA/DSC, and SEM were used to characterize the polymeric system. Swelling behavior, drug loading, and release pattern at pH of 5.5 and 7.4, irritation study, ex vivo drug permeation, and deposition study were also evaluated. RESULTS: Formed membranes were spherical, transparent, and had elasticity. The formation of a stable polymeric network was confirmed by structural and thermal analysis. Evaluation of the drug permeability in the skin showed good permeation and retention capabilities. No irritancy to the skin was observed. CONCLUSION: Based on the results obtained, the present study concluded that the formulated stable network might be an ideal network for the delivery of mupirocin in skin infections.

Synthesis of PEG-4000-co-poly (AMPS) nanogels by cross-linking polymerization as highly responsive networks for enhancement in meloxicam solubility.

Poor solubility is an ongoing issue and the graph of poorly soluble drugs has increased markedly which critically affect their dissolution, bioavailability, and clinical effects. This common issue needs to be addressed, for this purpose a series of polyethylene glycol (PEG-4000) based nanogels were developed by free radical polymerization technique to enhance the solubility, dissolution, and bioavailability of poorly soluble drug meloxicam (MLX), as improved solubility is the significant application of nanosystems. Developed nanogels formulations were characterized by FTIR, XRD, SEM, zeta sizer, percent equilibrium swelling, drug loaded content (DLC), drug entrapment efficiency (DEE), solubility studies, and in vitro dissolution studies. Furthermore, cytotoxicity studies were conducted in order to determine the bio-compatibility of the nanogels drug delivery system to biological environment. Nanogels particle size was found to be 156.19 ± 09.33 d.nm. Solubility study confirmed that the solubility of poorly soluble drug MLX was significantly enhanced up to 36 folds as compared to reference product (Mobic®). The toxicity study conducted on rabbits and MTT assay endorsed the safety of the developed nanogels formulations to the biological system.

Synthesis of novel combinatorial drug delivery system (nCDDS) for co-delivery of 5-fluorouracil and leucovorin calcium for colon targeting and controlled drug release.

OBJECTIVE: Purpose of the current study was to improve the oral effectiveness of 5-fluorouracil (5-FU) by developing novel controlled, combinatorial drug delivery system (nCDDS) for co-delivery of 5-FU and leucovorin calcium (LC) for colon targeting. SIGNIFICANCE: On the basis of results obtained, novel controlled, combinatorial drug delivery system could be an effective strategy for the colon targeting of 5-FU and LC. METHODS: Free radical polymerization method was tuned and used to fabricate this nCDDS. The nCDDS is synthesized in two steps, first synthesis of 5-FU/LC calcium loaded nanogels and second, pre-synthesized 5-FU and LC loaded nanogels were dispersed in pectin based polymerized matrix hard gel. The nanogels and nCDDS gels were characterized for network structure, thermal stability, and surface morphology. Swelling and in vitro release studies were carried out at different pH 1.2 and 7.4 both for naive nanogels and combined matrix gels. In vivo study of combinatorial gel was performed on rabbits by using HPLC method to estimate plasma drug concentration and pharmacokinetics parameters. RESULTS: Structure and thermal analysis confirmed the formation of stable polymeric network. SEM of nanogels and combinatorial gels showed that the spongy and rough edges particles and uniformly distributed in the combinatorial gel. The prepared nCDDS showed excellent water loving capacity and pH responsiveness. Combinatorial gel showed excellent characteristic for colonic delivery of drugs, which were confirmed by various in vitro and in vivo characterizations. Acute oral toxicity study of combinatorial gel confirmed the biocompatible and nontoxic characteristics of developed formulation. CONCLUSION: Conclusively, it can be found that nCDDS showed excellent properties regarding drug targeting in a controllable manner as compared to naive PEGylated nanogels.

Porous and highly responsive cross-linked ß-cyclodextrin based nanomatrices for improvement in drug dissolution and absorption.

AIMS: Aim of the study was to enhance the solubility of Chlorthalidone by developing beta-cyclodextrin cross-linked hydrophilic nanomatrices. MAIN METHODS: Nine different formulations were fabricated by free radical polymerization technique. All formulations were characterized through different studies. FTIR spectroscopy of unloaded and loaded nanomatrices was processed to determine compatibility of constituents and that of the drug with the system. Surface morphology of the nanomatrices was studied by SEM. The size of the optimized formulation was determined by zeta sizer. Swelling, in-vitro release and solubility studies were carried out in different media and results of in-vitro release profiles of nanomatrices and commercially available tablet of Chlorthalidone were compared. For determination of biocompatibility, toxicity studies were proclaimed in rabbits. KEY FINDINGS: Main peaks of corresponding functional groups of individual constituents and that of drug were depicted in FTIR spectra of unloaded and loaded nanomatrices. Porous and fluffy structure was visualized through SEM images. Particle size of the optimized formulation was in the range of 175 ± 5.27 nm. Percent loading of optimized formulation showed the best result. Comparing the in-vitro drug release profiles of nanomatrices and commercially available tablet, the results of the synthesized nanomatrices were quite satisfactory. Solubility profiles were also high as compared to the drug alone. Moreover, toxicity studies confirmed that nanomatrices were biocompatible and no sign of any toxic effect was found. SIGNIFICANCE: We concluded that our developed nanomatrices had successfully enhanced the solubility of Chlorthalidone and can also be used for other poorly aqueous soluble drugs.

Synthesis and evaluation of topical hydrogel membranes; a novel approach to treat skin disorders.

The aim of the study was to synthesize and evaluate chitosan-based topical cross-linked hydrogel membranes of mupirocin for new pharmaceutical controlled release application. These cross-linked structured membranes were synthesized by modification of free radical polymerization. Low molecular weight (LMW) chitosan is cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with a crosslinker N,N-methylenebisacrylamide (MBA). Hydrogel membranes were characterized by FTIR, DSC, TGA, SEM, Swelling behavior, sol-gel analysis, in vitro percent drug release at different pH, permeation across skin, ex vivo drug deposition study, irritation study and in vivo antibacterial activity of mupirocin loaded hydrogels. Developed membranes were spherical, adhesive and have good elastic strength. FTIR confirmed the cross-linking and formation of new structure having appropriate characteristics needed for controlled release delivery system. Drug release through rabbit's skin was evaluated by Franz diffusion cell and up to 6329.61 µg/1.5 cm2 was permeated and drug deposition in skin revealed significant retention up to 1224 µg/1.5 cm2. Formulated membranes were nonirritant to the skin as validated by Draize patch test. In surgical wound model, LMW chitosan-based hydrogel membranes showed prolong efficacy against bacterial infection caused by S. aureus. Enhanced retention of drug in skin demonstrated the good potential of topical delivery for skin bacterial infection.

Preparation and Evaluation of Skin Wound Healing Chitosan-Based Hydrogel Membranes.

The purpose of the study was to synthesize and characterize a new form of topical membranes as chitosan-based hydrogel membranes for bacterial skin infections. The polymeric membranes were synthesized by modification in free radical solution polymerization technique. High molecular weight (HMW) chitosan polymer was cross-linked with monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS) through cross-linker N,N-methylenebisacrylamide (MBA). Mupirocin, an antibiotic, was used as model drug. The polymeric membranes were prepared in spherical form that found stable and elastic. Characterization of hydrogel membranes was performed by FTIR, SEM, DSC, TGA, swelling behavior, drug release, irritation study, and ex vivo drug permeation and deposition study. Structural and thermal studies confirmed the formation of new polymeric network with enhanced stability of hydrogel membranes. Permeation flux of drug from optimized formulation through rabbit's skin assessed by using Franz cell was up to 104.09 µg cm-2 h-1. Furthermore, hydrogel membrane has significant retention of drug in skin up to 2185 µg 1.5 cm-2. Draize patch test confirmed the synthesized hydrogels as non-irritant to skin. The preparation of a topical membrane with improved antibacterial activity within controlled release manner is desirable for the advancement and treatment of skin diseases.