MyMedR

Displaying all 8 publications

Abstract:

Sort:

Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles

Siddique MI, Katas H, Amin MCIM, Ng SF, Zulfakar MH, Buang F, et al.

J Pharm Sci, 2015 Dec;104(12):4276-4286.
PMID: 26447747 DOI: 10.1002/jps.24666

Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.
Simvastatin nanoparticles loaded polymeric film as a potential strategy for diabetic wound healing: in vitro and in vivo evaluation

Tufail S, Siddique MI, Sarfraz M, Sohail MF, Shahid MN, Omer MO, et al.

Curr Drug Deliv, 2021 Jul 20.
PMID: 34288836 DOI: 10.2174/1567201818666210720150929

INTRODUCTION: The pleiotropic effects of statins are recently explored for wound healing through angiogenesis and lymph-angiogenesis that could be of great importance in diabetic wounds.
AIM: Aim of the present study is to fabricate nanofilm embedded with simvastatin loaded chitosan nanoparticles (CS-SIM-NPs) has been reported herein to explore the efficacy of SIM in diabetic wound healing.
METHODS: The NPs, prepared via ionic gelation, were 173nm ± 2.645 in size with a zeta potential -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats.
RESULTS: The results showed significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site.
CONCLUSION: Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.
In-vivo dermal pharmacokinetics, efficacy, and safety of skin targeting nanoparticles for corticosteroid treatment of atopic dermatitis

Siddique MI, Katas H, Amin MC, Ng SF, Zulfakar MH, Jamil A

Int J Pharm, 2016 Jun 30;507(1-2):72-82.
PMID: 27154252 DOI: 10.1016/j.ijpharm.2016.05.005

The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
Towards fast and cost-effective up-scaling of Nano-encapsulations by Ionic-gelation method using model drug for the treatment of atopic dermatitis

Siddique MI, Tufail S, Ker ZH, Khan TM, Rasool F, Sohail MF, et al.

Pak J Pharm Sci, 2019 Sep;32(5(Supplementary)):2299-2304.
PMID: 31894058

Chitosan nanoparticles (CSNPs) have proven their excellent drug delivery potential through various routes of administration and therefore, the need for large scale production of CSNPs for the commercialization is paramount. Their particle size and surface charge, drug loading capacity, and morphology were characterized in this study. Finally, drug release studies of both continuous and scalable modes were undertaken to ascertain suitability of CSNPs as a carrier for HC. The particle size of the large and small scale of HC-CSNPs was 253.3±16.4 nm and 225.4 ±9.6 nm, respectively. Besides, the surface charge of the large and small scale of HC-CSNPs was +35.3±0.3 mV and +32.6±2.5 mV, respectively. The size and surface charge of both HC-CSNPs were not proven to be statistically different. Drug loading capacity of large and small scale production of HC-CSNPs was high with 89%, and 83% of HC was loaded into CSNPs, respectively. Moreover, the morphology of both large and small scale production of HC-CSNPs had a similar shape and particle size. The drug release profile of CSNPs prepared by both methods showed a significantly (p<0.05) higher percentage release as compared to the free form. It is expected that positively charged nano-sized HC-CSNPs with high drug loading capacity could enhance the efficiency of drug delivery system to carry and diffuse into the target cells. The results obtained also suggested that the modified method applied could be further developed for large scale production of HC-CSNPs.
Fabrication and characterization of matrix type transdermal patches loaded with tizanidine hydrochloride: potential sustained release delivery system

Shahid N, Siddique MI, Razzaq Z, Katas H, Waqas MK, Rahman KU

Drug Dev Ind Pharm, 2018 Dec;44(12):2061-2070.
PMID: 30081679 DOI: 10.1080/03639045.2018.1509081

OBJECTIVE: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.
SIGNIFICANCE: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.
METHODS: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.
RESULTS: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.
CONCLUSIONS: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.
Oral Dispersible Films from Product Development to End-User Acceptability: A Review

Khan QU, Siddique MI, Sarfraz M, Rehman K, Sohail MF, Katas H

Crit Rev Ther Drug Carrier Syst, 2022;39(1):33-64.
PMID: 34936317 DOI: 10.1615/CritRevTherDrugCarrierSyst.2021036885

Orodispersible films (ODFs) have served as an emerging platform for the delivery of drugs in a convenient way. They have numerous advantages, the significant one is simplicity of administration for special populations such as pediatric and geriatric as well as patients with swallowing difficulty. Besides, the advantages include accurate dosing and fast action. The ODFs are efficiently designed with detailed knowledge of drug and polymers as well as a suitable selection of method. Many conventional and advance formulation strategies have been used for the development of ODFs. The biopharmaceutical concerns of active pharmaceutical ingredients (APIs) are given in this review in light of the fact that ODFs can be utilized to increase the bioavailability of APIs. The basic critical issues such as good mechanical properties, water solubility of the API and taste masking are very important to be considered during the development of ODFs. The knowledge of critical quality concerns of ODFs will be helpful in the future development of ODF. As ODFs remain in the mouth until complete degradation, taste, texture and mouth-feel are the qualities that in all respects liable for acceptability of the patient. An assortment of packaging choices is also accessible for ODFs. This review focuses on the different critical concerns of ODF related to composition, bio-pharmaceutical, manufacturing, quality tests, packaging and acceptability. Additionally, potential barriers in the ODFs development are discussed in details. Therefore, this review is an informative bundle of ODFs concerns from the product development stage to the end-user acceptability.
Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects

Siddique MI, Katas H, Jamil A, Mohd Amin MCI, Ng SF, Zulfakar MH, et al.

Drug Deliv Transl Res, 2019 04;9(2):469-481.
PMID: 29159691 DOI: 10.1007/s13346-017-0439-7

Hydrocortisone (HC), topical glucocorticoid along with hydroxytyrosol (HT), and anti-microbial- and anti-oxidant-loaded chitosan nanoparticles (CSNPs) were prepared in large scale and analyzed for their adverse effects on healthy human skin followed by repeated applications. Ten subjects were randomized to receive test (HC-HT CSNPs) and vehicle samples (aqueous (AQ) cream). They were applied on the arms for 28 days, and transepidermal water loss (TEWL), erythema intensity, and irritation score were measured. Blood samples were analyzed for blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone (ACTH) levels. Skin biopsy was obtained to assess histopathological changes in the skin. HC-HT CSNP AQ cream was stored at 4, 25, and 45 °C for a period of 1 year, and its stability was assessed by monitoring their physical appearances, particle size, and pH. Spherical-shaped NPs were successfully upscaled using spinning-disc technology, with insignificant changes in particle size, zeta potential, and incorporation of drugs as compared to the well-established laboratory method. Particle size of HC-HT CSNPs was
Thermoresponsive curcumin/DsiRNA nanoparticle gels for the treatment of diabetic wounds: synthesis and drug release

Katas H, Wen CY, Siddique MI, Hussain Z, Mohd Fadhil FH

Ther Deliv, 2017 01;8(3):137-150.
PMID: 28145827 DOI: 10.4155/tde-2016-0075

AIM: Chitosan (CS) has been extensively studied as drug delivery systems for wound healing. Results/methodology: CS nanoparticles were loaded with curcumin (Cur) and DsiRNA against prostaglandin transporter gene and they were incorporated into 20 and 25% w/v Pluronic F-127. The gels were later analyzed for their rheology, gelation temperature (Tgel), morphology, drug incorporation and in vitro drug release. The particle size was in the range of 231 ± 17-320 ± 20 nm, depending on CS concentration. The gels had Tgel of 23-28°C and exhibited sustained drug release with high accumulated amount of drugs over 48 h.
CONCLUSION: A thermo-sensitive gel containing Cur/DsiRNA CS nanoparticles was successfully developed and has a great potential to be further developed.