Enhanced drug delivery and wound healing potential of berberine-loaded chitosan-alginate nanocomposite gel: characterization and in vivo assessment

被引:4
作者
Akhter, Md Habban [1 ]
Al-Keridis, Lamya Ahmad [2 ]
Saeed, Mohd [3 ]
Khalilullah, Habibullah [4 ]
Rab, Safia Obaidur [5 ]
Aljadaan, Adel M. [6 ,7 ]
Rahman, Mohammad Akhlaquer [8 ]
Jaremko, Mariusz [9 ]
Emwas, Abdul-Hamid [10 ]
Ahmad, Sarfaraz [11 ]
Alam, Nawazish [11 ]
Ali, Md Sajid [12 ]
Khan, Gyas [13 ]
Afzal, Obaid [14 ]
机构
[1] DIT Univ, Sch Pharmaceut & Populat Hlth Informat SoPPHI, Dehra Dun, India
[2] Princess Nourah Bint Abdulrahman Univ, Fac Sci, Dept Biol, Riyadh, Saudi Arabia
[3] Univ Hail, Coll Sci, Dept Biol, Hail, Saudi Arabia
[4] Qassim Univ, Dept Pharmaceut Chem & Pharmacognosy, Unaizah Coll Pharm, Unaizah, Saudi Arabia
[5] King Khalid Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Abha, Saudi Arabia
[6] Najran Univ, Coll Pharm, Dept Pharmacol, Najran, Saudi Arabia
[7] Univ Nottingham Grad Entry Med, Royal Derby Hosp, Nottingham, England
[8] Taif Univ, Coll Pharm, Dept Pharmaceut & Ind Pharm, Taif, Saudi Arabia
[9] King Abdullah Univ Sci & Technol KAUST, Div Biol & Environm Sci & Engn BESE, Thuwal, Saudi Arabia
[10] King Abdullah Univ Sci & Technol KAUST, Core Labs, Thuwal, Saudi Arabia
[11] Jazan Univ, Coll Pharm, Dept Clin Pharm Practice, Jazan, Saudi Arabia
[12] Jazan Univ, Coll Pharm, Dept Pharmaceut, Jazan, Saudi Arabia
[13] Jazan Univ, Coll Pharm, Dept Pharmacol & Toxicol, Jazan, Saudi Arabia
[14] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmaceut Chem, Al Kharj, Saudi Arabia
关键词
wound healing; polymer; nanomedicine; nanotechnology; chitosan; alginate; nanocomposite; berberine; NANOPARTICLES; CANCER; OPTIMIZATION; HYDROGEL; VITRO;
D O I
10.3389/fpubh.2023.1238961
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Berberine-encapsulated polyelectrolyte nanocomposite (BR-PolyET-NC) gel was developed as a long-acting improved wound healing therapy. BR-PolyET-NC was developed using an ionic gelation/complexation method and thereafter loaded into Carbopol gel. Formulation was optimized using Design-Expert (R) software implementing a three-level, three-factor Box Behnken design (BBD). The concentrations of polymers, namely, chitosan and alginate, and calcium chloride were investigated based on particle size and %EE. Moreover, formulation characterized in vitro for biopharmaceutical performances and their wound healing potency was evaluated in vivo in adult BALB/c mice. The particle distribution analysis showed a nanocomposite size of 71 +/- 3.5 nm, polydispersity index (PDI) of 0.45, zeta-potential of +22 mV, BR entrapment of 91 +/- 1.6%, and loading efficiency of 12.5 +/- 0.91%. Percentage drug release was recorded as 89.50 +/- 6.9% with pH 6.8, thereby simulating the wound microenvironment. The in vitro investigation of the nanocomposite gel revealed uniform consistency, well spreadability, and extrudability, which are ideal for topical wound use. The analytical estimation executed using FT-IR, DSC, and X-ray diffraction (XRD) indicated successful formulation with no drug excipients and without the amorphous state. The colony count of microbes was greatly reduced in the BR-PolyET-NC treated group on the 15th day from up to 6 CFU compared to 20 CFU observed in the BR gel treated group. The numbers of monocytes and lymphocytes counts were significantly reduced following healing progression, which reached to a peak level and vanished on the 15th day. The observed experimental characterization and in vivo study indicated the effectiveness of the developed BR-PolyET-NC gel toward wound closure and healing process, and it was found that >99% of the wound closed by 15th day, stimulated via various anti-inflammatory and angiogenic factors.
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页数:16
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