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1. ASSIGNMENT 1
Dosage Form Lab
Prepared by :munazza naveed
Submitted to proff:Mohammad Farhan Ali Khan
Section 2:
Bph243072
MRSA wound infections
Methicillin-resistant Staphylococcus aureus (MRSA) is a Gram-positive bacterium frequently
found in skin/soft-tissue infections (surgical sites, diabetic foot ulcers, burns, trauma).
MRSA’s resistance to beta-lactam antibiotics and its frequent ability to form biofilms on
wound surfaces are major reasons systemic antibiotics often fail to eradicate infection and
heal wounds. Biofilms protect bacteria inside an extracellular polymeric substance (EPS),
reducing antibiotic penetration and enabling persister cells that survive treatment.

2. Chosen dosage form:
Topical hydrogel dressing that contains antimicrobial nanoparticles and/or antibiotic-loaded
nanoparticles (examples: silver nanoparticles, zinc oxide nanoparticles, chitosan
nanoparticles, liposomal or polymeric nanoparticles loaded with vancomycin or other anti-
MRSA agents) — applied directly to the wound as a dressing that provides sustained local
release.
Why this dosage form is the best choice ?
A.Local, high-concentration therapy at the infection site
Topical hydrogel places antimicrobial agents directly where bacteria live — achieving
concentrations in the wound that are much higher than what is safe systemically, improving
bacterial kill while avoiding systemic toxicity (e.g., nephrotoxicity from IV vancomycin).
This is particularly important for MRSA where high local concentration matters.
B.Penetration and disruption of biofilms
Nanoparticles are small enough and can be surface-modified (e.g., positive surface charge) to
penetrate EPS and reach biofilm-embedded bacteria. Some NPs (metal NPs, cationic
polymeric NPs) also disrupt EPS structure, increasing antibiotic susceptibility. Combining
nanoparticles with antibiotics (co-delivery) both physically disrupts biofilm and delivers
antibiotic payload into the interior.
C.Multifunctional antimicrobial action — lowers resistance risk
Metal nanoparticles (silver, zinc oxide) have multiple bactericidal mechanisms — membrane
damage, generation of reactive oxygen species, protein/DNA interactions — that make it
harder for bacteria to develop single-mutation resistance compared with single-target
antibiotics. When nanoparticles are combined with antibiotics, synergistic effects can reduce
required antibiotic dose.

3. D. Moist wound healing + tissue support
Hydrogels maintain a moist environment, which accelerates granulation and re-
epithelialization. Hydrogels can also be designed to support cell migration, release growth
factors, or include anti-inflammatory agents — roles that simple creams/ointments don’t
provide.
E.Sustained and controlled release (drug)delivery advantage)
Hydrogels act as a depot for nanoparticles that release drug gradually — reducing frequency
of dressing changes, maintaining therapeutic concentration over time, and improving patient
compliance relative to frequent topical ointment reapplication or systemic dosing.
Vancomycin and other antibiotics have been successfully incorporated into hydrogels for
prolonged local delivery in recent studies.
How it compares to common marketed alternatives (creams, ointments, systemic
antibiotics)?
Oral/IV antibiotics: Good for systemic infection or sepsis, but may provide insufficient local
concentration in biofilm, carry systemic side effects (renal, GI), and drive resistance. Topical
hydrogel reduces systemic exposure while maximizing local effect. Simple topical
creams/ointments (e.g., mupirocin, fusidic acid, silver sulfadiazine): Often short-acting, poor
biofilm penetration, limited sustained release, can be washed away or fail to maintain moist
environment. Nanoparticle hydrogels provide biofilm disruption, sustained release, and
wound-healing support. Commercial antimicrobial dressings (e.g., silver-impregnated
dressings): Useful, but many are passive reservoirs with limited controlled release or
insufficient penetration into thick biofilm. Nanosystems can be engineered for targeted
penetration and triggered release.
Mechanisms of action :
Nanoparticles physically/chemically disrupt biofilm matrix — positive charge interacts with
anionic EPS; small size enables diffusion into EPS and close contact with bacterial cells.
Intrinsic nanoparticle antimicrobial effects — metals (Ag, ZnO) produce ROS, disrupt
membranes, bind proteins/DNA. Chitosan exerts membrane disruption and chelates metals.

4. Antibiotic delivery — nanoparticles or liposomes can encapsulate antibiotics (e.g.,
vancomycin) and release them in a sustained or stimuli-responsive manner, increasing local
drug levels and reducing systemic exposure.
Synergy — NP-mediated membrane damage can increase antibiotic uptake into bacteria; NP
action on EPS weakens biofilm defenses.
Formulation components & practical design choices:
Hydrogel matrix: Natural polymers (chitosan, gelatin, alginate), synthetic (PEG, Pluronic,
polyacrylamide) or hybrid. Chitosan is attractive due to innate antimicrobial and wound-
healing properties.
Inorganic: silver nanoparticles (AgNPs), zinc oxide (ZnO), iron oxide — strong antimicrobial
but need toxicity evaluation.
Organic/polymeric: chitosan nanoparticles, PLGA, liposomes — better biocompatibility and
drug loading for antibiotics.
Antibiotic-loaded nanoparticles: vancomycin-loaded liposomes/NPs (effective versus MRSA
in wound models).
Additives: crosslinkers for mechanical strength, pores for oxygen diffusion, growth factors or
anti-inflammatories for tissue repair.
Release control: tune NP composition, polymer crosslink density, or use stimuli-responsive
linkers (pH, enzymes) to trigger release in infected wounds.
Clean wound per normal wound care; apply hydrogel layer to fill wound bed and cover with
secondary dressing as needed.Frequency: many sustained-release hydrogels in studies are
changed every 2–3 days or as indicated by exudate; some formulations show efficacy for 7+
days in animal models. Exact regimen depends on release kinetics and clinical judgment.
Ten References :
1)Teo, M. Z. Y., et al. (2025). Progress in topical nanoformulations against bacterial skin
infections. Drug Delivery and Translational Research.
2)Chegini, Z., et al. (2024). Antibacterial and antibiofilm activity of silver nanoparticles:
applications in wound healing. Scientific Reports.

5. 3)Sun, S., et al. (2024). Vancomycin-loaded in situ gelled hydrogel as an effective local
delivery system for MRSA wounds. Journal of Controlled Release / PMC.
4)Rajkumar, D. S. R., et al. (2024). Chitosan-based biomaterials in wound healing: a
review. International Journal of Biological Macromolecules / PMC.
5)Zhang, X., et al. (2022). Current progress and outlook of nano-based hydrogels for wound
healing. Frontiers/PMC.
6)Hwang, J., et al. (2023). Controlled delivery of vancomycin from collagen-tethered
nanovesicles: improved MRSA inhibition in wound models. Molecular Pharmaceutics /
ACS.
7)Rodrigues, M., et al. (2023). Nanomaterial-enabled anti-biofilm strategies: new
opportunities for wound therapy. Nanomedicine Reviews.
8)Abdullahi, N., et al. (2023). How nanoparticles help in combating chronic wound
biofilms. Biomaterials Reviews / PMC.
9)Khalifa, H. O., et al. (2025). Silver nanoparticles as next-generation antimicrobial agents:
opportunities and challenges. Frontiers in Cellular and Infection Microbiology.
10)Hwang, J., et al. (2023). Controlled delivery of vancomycin from collagen-tethered
nanovesicles: efficacy in MRSA wound infection (ACS Molecular Pharmaceutics).