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1.
Carbohydr Polym ; 317: 121085, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37364955

ABSTRACT

The management of deep burn injuries is extremely challenging, ascribed to their delayed wound healing rate, susceptibility for bacterial infections, pain, and increased risk of hypertrophic scarring. In our current investigation, a series of composite nanofiber dressings (NFDs) based on polyurethane (PU) and marine polysaccharides (i.e., hydroxypropyl trimethyl ammonium chloride chitosan, HACC and sodium alginate, SA) were accomplished by electrospinning and freeze-drying protocols. The 20(R)-ginsenoside Rg3 (Rg3) was further loaded into these NFDs to inhibit the formation of excessive wound scars. The PU/HACC/SA/Rg3 dressings showed a sandwich-like structure. The Rg3 was encapsulated in the middle layers of these NFDs and slowly released over 30 days. The PU/HACC/SA and PU/HACC/SA/Rg3 composite dressings demonstrated superior wound healing potentials over other NFDs. These dressings also displayed favorable cytocompatibility with keratinocytes and fibroblasts and could dramatically accelerate epidermal wound closure rate following 21 days of the treatment of a deep burn wound animal model. Interestingly, the PU/HACC/SA/Rg3 obviously reduced the excessive scar formation, with a collagen type I/III ratio closer to the normal skin. Overall, this study represented PU/HACC/SA/Rg3 as a promising multifunctional wound dressing, which promoted the regeneration of burn skins and attenuated scar formation.


Subject(s)
Burns , Nanofibers , Animals , Cicatrix , Polyurethanes , Wound Healing , Burns/drug therapy , Alginates/pharmacology , Bandages
2.
Carbohydr Polym ; 312: 120797, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37059536

ABSTRACT

Now-a-days, the polysaccharides are extensively employed for the delivery of small-molecule drugs ascribed to their excellent biocompatibility, biodegradability and modifiability. An array of drug molecules is often chemically conjugated with different polysaccharides to augment their bio-performances. As compared to their therapeutic precursors, these conjugates could typically demonstrate an improved intrinsic solubility, stability, bioavailability and pharmacokinetic profiles of the drugs. In current years, various stimuli-responsive particularly pH and enzyme-sensitive linkers or pendants are also exploited to integrate the drug molecules into the polysaccharide backbone. The resulting conjugates could experience a rapid molecular conformational change upon exposure to the microenvironmental pH and enzyme changes of the diseased states, triggering the release of the bioactive cargos at the targeted sites and eventually minimize the systemic side effects. Herein, the recent advances in pH and enzyme -responsive polysaccharide-drug conjugates and their therapeutic benefits are systematically reviewed, following a brief description on the conjugation chemistry of the polysaccharides and drug molecules. The challenges and future perspectives of these conjugates are also precisely discussed.


Subject(s)
Drug Delivery Systems , Drug-Related Side Effects and Adverse Reactions , Humans , Pharmaceutical Preparations , Drug Delivery Systems/methods , Polysaccharides/chemistry , Hydrogen-Ion Concentration , Drug Carriers/chemistry
3.
Asian J Pharm Sci ; 18(6): 100856, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38204470

ABSTRACT

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management. In this study, a greater efficacy in burn wound healing and the associated mechanisms of α-lactalbumin (ALA) based electrospun nanofibrous scaffolds (ENs) as compared to other regenerative protein scaffolds were established. Bovine serum albumin (BSA), collagen type I (COL), lysozyme (LZM) and ALA were separately blended with poly(ε-caprolactone) (PCL) to fabricate four different composite ENs (LZM/PCL, BSA/PCL, COL/PCL and ALA/PCL ENs). The hydrophilic composite scaffolds exhibited an enhanced wettability and variable mechanical properties. The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs. As compared to PCL ENs and other composite scaffolds, the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen spongeⓇ on third-degree burn model. The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites. Collectively, this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.

4.
Int J Biol Macromol ; 181: 169-179, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-33775757

ABSTRACT

Curdlan (CN)-doped montmorillonite/poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide) [CN/MT/P(NIPA-co-MBA)] smart nanocomposites (NCs) were developed for efficient erlotinib HCl (ERL) delivery to lung cancer cells. The placebo NCs demonstrated excellent biodegradability, pH/thermo-responsive swelling profiles and declined molar mass (M¯c) between the crosslinks with increasing temperature. The XRD, FTIR, DSC, TGA, and SEM analyses revealed the architectural chemistry of these NC scaffolds. The NCs loaded with ERL (F-1-F-3) displayed acceptable diameter (734-1120 nm) and zeta potential (+1.16 to -11.17 mV), outstanding drug entrapping capability (DEE, 78-99%) and sustained biphasic ERL elution patterns (Q8h, 53-91%). The ERL release kinetics of the optimal matrices (F-3) obeyed Higuchi model and their transport occurred through anomalous diffusion. The mucin adsorption behaviour of these matrices followed Freudlich isotherms. As compared to pure ERL, the formulation (F-3) displayed an improved anti-proliferative potential and induced apoptosis more effectively on A549 cells. Thus, the CN-doped smart NCs could be utilized as promising drug-cargoes for lung cancer therapy.


Subject(s)
Erlotinib Hydrochloride/pharmacology , Nanocomposites/chemistry , beta-Glucans/chemistry , A549 Cells , Acrylamides/chemical synthesis , Acrylamides/chemistry , Adsorption , Bentonite/chemical synthesis , Bentonite/chemistry , Cell Survival/drug effects , Drug Liberation , Endocytosis/drug effects , Humans , Hydrogen-Ion Concentration , Kinetics , Mucins/metabolism , Particle Size , Spectroscopy, Fourier Transform Infrared , Staining and Labeling , Static Electricity , Temperature , Thermogravimetry , X-Ray Diffraction
5.
Mater Sci Eng C Mater Biol Appl ; 110: 110628, 2020 May.
Article in English | MEDLINE | ID: mdl-32204068

ABSTRACT

The current study dealt with the synthesis and characterization of carboxymethyl fenugreek galactomannang-g-poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide)-bentonite [CFG-g-P(NIPA-co-MBA)-BEN] based nanocomposites (NCs) as erlotinib (ERL)-delivery devices for lung cancer cells to suppress excessive cell proliferation. The blank NCs exhibited outstanding biodegradability and pH/temperature-dependent swelling profiles, which were significantly influenced by their BEN contents (0-20%). The molar mass (M¯c) between the crosslinks of these NCs was declined with temperature. The composite architecture of these scaffolds was confirmed by XRD, FTIR, TGA, DSC and SEM analyses. The corresponding ERL-loaded matrices (F-1-F-3) portrayed outstanding drug encapsulation efficiency (DEE, 93-100%) with zeta potential between -8 and -16 mV and diameter between 615 and 1258 nm. These formulations demonstrated sustained ERL elution profiles (Q8h, 62-98%) with an initial burst release of drug. The drug dissolution pattern of the optimized matrices (F-3) obeyed first-order kinetic model and was driven by Fickian diffusion. The mucin adsorption behavior of F-3 was best fitted to Freudlich isotherms. The ERL-loaded formulation suppressed A549 cell proliferation and promoted apoptosis to a greater extent than the pristine drug, as detected by cellular uptake analysis, MTT cytotoxicity test and AO/EB staining assay.


Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Drug Carriers , Hot Temperature , Lung Neoplasms/drug therapy , Models, Chemical , A549 Cells , Acrylamides/chemistry , Acrylamides/pharmacokinetics , Acrylamides/pharmacology , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Galactose/analogs & derivatives , Humans , Hydrogen-Ion Concentration , Lung Neoplasms/metabolism , Mannans/chemistry , Mannans/pharmacokinetics , Mannans/pharmacology
6.
Carbohydr Polym ; 230: 115664, 2020 Feb 15.
Article in English | MEDLINE | ID: mdl-31887927

ABSTRACT

Erlotinib-loaded carboxymethyl temarind gum-g-poly(N-isopropylacrylamide)-montmorillonite based semi-IPN nanocomposites were synthesized and characterized for their in vitro performances for lung cancer therapy. The placebo matrices exhibited outstanding biodegradability and pH-dependent swelling profiles. The molar mass (M¯ c) between the crosslinks of these composites was declined with temperature. The solid state characterization confirmed the semi-IPN architecture of these scaffolds. The corresponding drug-loaded formulations displayed excellent drug-trapping capacity (DEE, 86-97 %) with acceptable zeta potential (-16 to -13 mV) and diameter (967-646 nm). These formulations conferred sustained drug elution profiles (Q8h, 77-99 %) with an initial burst release. The drug release profile of the optimized formulation (F-3) was best fitted in the first order kinetic model with Fickian diffusion driven mechanism. The mucin adsorption to F-3 followed Langmuir isotherms. The results of MTT assay, AO/EB staining and confocal analyses revealed that the ERL-loaded formulation suppressed A549 cell proliferation and induced apoptosis more effectively than pristine drug.


Subject(s)
Drug Carriers/chemistry , Erlotinib Hydrochloride/administration & dosage , Nanocomposites/chemistry , A549 Cells , Drug Carriers/therapeutic use , Drug Liberation , Humans , Lung Neoplasms/drug therapy , Nanocomposites/therapeutic use
7.
Int J Biol Macromol ; 129: 552-563, 2019 May 15.
Article in English | MEDLINE | ID: mdl-30707999

ABSTRACT

Novel diethanolamine-grafted high-methoxyl pectin (DGP)-arabic gum (AG) modified montmorillonite (MMT) composites were developed for intragastric ziprasidone HCl (ZIP) delivery by combining floating and mucoadhesion mechanisms. The ZIP-loaded clay-biopolymer matrices were accomplished by ionotropic gelation protocol utilizing zinc acetate in the presence or absence of covalent crosslinker, glutaraldehyde (GA). Various formulations exhibited excellent drug entrapment efficiency (DEE, %) and sustained drug release profiles, which were influenced by the polymer-blend (DGP:AG) ratios, reinforcing filler (MMT) existence and crosslinking procedure. The optimal composites (F-3) demonstrated DEE of 61% and Q8h of 52% with outstanding buoyancy, mucin adsorption ability and biodegradability. The release profile of F-3 was best fitted in the Korsmeyer-Peppas model with Fickian diffusion driven mechanism. The mucin adsorption to composites F-3 followed Freundlich isotherms. The molar mass between crosslinks of composites (F-3) calculated employing Flory-Rehner equation was increased with temperature. Moreover, the thermal, X-ray and infrared analyses confirmed a compatible environment of drug in the composites, except certain extent of transformation of the crystalline drug to its amorphous form. The SEM studies revealed the spherical morphology of the composites. Thus, the newly developed DGP-AG-MMT composites are appropriate for gastroretentive ZIP delivery over an extended period of time.


Subject(s)
Bentonite/chemistry , Drug Carriers/chemistry , Drug Carriers/metabolism , Gastric Mucosa/metabolism , Gum Arabic/chemistry , Pectins/chemistry , Piperazines/chemistry , Thiazoles/chemistry , Adhesiveness , Adsorption , Drug Liberation , Surface Properties
8.
Diabetes Metab Syndr ; 12(6): 1057-1063, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30017505

ABSTRACT

Diabetes is among leading public health concerns in Malaysia due to premature and preventable mortality involving macro and microvascular complications. Diabetes knowledge, attitude, and practice (KAP) are vital in diabetes management. The present study assessed the level of diabetes KAP among type 2 diabetes patients with associated and correlated factors through a self-administered questionnaire-based study on a convenience sample of 386 type 2 diabetes mellitus patients in Kuala Muda District, Kedah, Malaysia. Majority of the respondents possessed levels above the cut-off points for poor levels in knowledge (63.21%), attitude (62.69%), and practices (58.03%). Age, academic qualification, occupation, monthly income, current therapy type, comorbid diseases, and therapy preference were associated with KAP whereas the associations of disease duration, the best source of information about diabetes, and health status satisfaction were witnessed for attitude and practice. Academic qualification had strongest correlation for knowledge (r = 0.785), attitude (r = 0.725), and practice (r = 0.709). Knowledge level was significantly correlated with attitude level (r = 0.735), practice level (r = 0.786), income (r = 0.556), occupation (r = 0.358), age (r = 0.173), current therapy type (r = 0.133), and diabetes education exposure (r = 0.113). Attitude level had significant correlations with practice level (r = 0.679), income (r = 0.357), occupation (r = 0.348), health status satisfaction (r = 0.147), age (r = 0.145), and gender (r = 0.109). Practice level correlated significantly with income (r = 0.448), occupation (r = 0.317), age (r = 0.173), health status satisfaction (r = 0.167), and current therapy type (r = 0.118). All associations and correlations were significant at P < 0.005. Although overall having good levels of diabetes KAP, educational interventions are required to further improve diabetes KAP.


Subject(s)
Diabetes Mellitus, Type 2 , Health Knowledge, Attitudes, Practice , Adult , Aged , Cross-Sectional Studies , Female , Humans , Malaysia , Male , Middle Aged
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